FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Jones, CK Engers, DW Thompson, AD Field, JR Blobaum, AL Lindsley, SR Zhou, Y Gogliotti, RD Jadhav, S Zamorano, R Bogenpohl, J Smith, Y Morrison, R Daniels, JS Weaver, CD Conn, PJ Lindsley, CW Niswender, CM Hopkins, CR AF Jones, Carrie K. Engers, Darren W. Thompson, Analisa D. Field, Julie R. Blobaum, Anna L. Lindsley, Stacey R. Zhou, Ya Gogliotti, Rocco D. Jadhav, Satyawan Zamorano, Rocio Bogenpohl, Jim Smith, Yoland Morrison, Ryan Daniels, J. Scott Weaver, C. David Conn, P. Jeffrey Lindsley, Craig W. Niswender, Colleen M. Hopkins, Corey R. TI Discovery, Synthesis, and Structure-Activity Relationship Development of a Series of N-4-(2,5-Dioxopyrrolidin-1-yl)phenylpicolinamides (VU0400195, ML182): Characterization of a Novel Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 4 (mGlu(4)) with Oral Efficacy in an Antiparkinsonian Animal Model SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PARKINSONS-DISEASE; MGLUR4; PHARMACOLOGY; DOPAMINE; LEVODOPA; PAMS AB There is an increasing amount of literature data showing the positive effects on preclinical antiparkinsonian rodent models with selective positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)). However, most of the data generated utilize compounds that have not been optimized for druglike properties, and as a consequence, they exhibit poor pharmacokinetic properties and thus do not cross the blood-brain barrier. Herein, we report on a series of N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides with improved PK properties with excellent potency and selectivity as well as improved brain exposure in rodents. Finally, ML182 was shown to be orally active in the haloperidol induced catalepsy model, a well-established antiparkinsonian model. C1 [Jones, Carrie K.; Engers, Darren W.; Thompson, Analisa D.; Field, Julie R.; Blobaum, Anna L.; Lindsley, Stacey R.; Zhou, Ya; Gogliotti, Rocco D.; Jadhav, Satyawan; Zamorano, Rocio; Morrison, Ryan; Daniels, J. Scott; Weaver, C. David; Conn, P. Jeffrey; Lindsley, Craig W.; Niswender, Colleen M.; Hopkins, Corey R.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Jones, Carrie K.; Engers, Darren W.; Thompson, Analisa D.; Blobaum, Anna L.; Lindsley, Stacey R.; Zhou, Ya; Gogliotti, Rocco D.; Jadhav, Satyawan; Zamorano, Rocio; Morrison, Ryan; Daniels, J. Scott; Conn, P. Jeffrey; Lindsley, Craig W.; Niswender, Colleen M.; Hopkins, Corey R.] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA. [Jones, Carrie K.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. [Lindsley, Craig W.; Hopkins, Corey R.] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA. [Weaver, C. David; Conn, P. Jeffrey; Lindsley, Craig W.] Vanderbilt Univ, Vanderbilt Inst Chem Biol, Nashville, TN 37232 USA. [Engers, Darren W.; Conn, P. Jeffrey; Lindsley, Craig W.; Hopkins, Corey R.] Vanderbilt Specialized Chem Ctr Accelerated Probe, Nashville, TN 37232 USA. [Bogenpohl, Jim; Smith, Yoland] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. [Bogenpohl, Jim; Smith, Yoland] Emory Univ, Dept Neurol, Atlanta, GA 30329 USA. RP Niswender, CM (reprint author), Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. EM colleen.niswender@vanderbilt.edu; corey.r.hopkins@vanderbilt.edu RI Conn, Peter/D-7848-2012; Zhou, Ya/F-1220-2013 FU National Institute of Mental Health, National Institute of Neurological Disorders and Stroke; Micheal J. Fox Foundation; Vanderbilt Department of Pharmacology; Vanderbilt Institute of Chemical Biology; NIH/MLPCN [5U54MH08465-02] FX The authors warmly acknowledge Emily L. Days, Tasha Nalywajko, Cheryl A. Austin, and Michael Baxter Williams for their critical contributions to the HTS portion of the projects; Matt Mulder, Chris Denicola, Nathan Kett, and Sichen Chang for the purification of compounds utilizing the mass-directed HPLC system; and Katrina Brewer for technical assistance with the PK assays. The dog cassette in vivo experiment was performed at Calvert Labs, and the rhesus in vivo experiment was performed at the Yerkes Primate Center at Emory University, GA. This work was supported by the National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, the Micheal J. Fox Foundation, the Vanderbilt Department of Pharmacology, and the Vanderbilt Institute of Chemical Biology. In addition, the authors thank the NIH/MLPCN (Grant 5U54MH08465-02) for support of this research. Vanderbilt is a member of the MLPCN and houses the Vanderbilt Specialized Chemistry Center for Accelerated Probe Development. NR 27 TC 35 Z9 36 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 10 PY 2011 VL 54 IS 21 BP 7639 EP 7647 DI 10.1021/jm200956q PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 839ZN UT WOS:000296408100018 PM 21966889 ER PT J AU Mizukawa, B Wei, JP Shrestha, M Wunderlich, M Chou, FS Griesinger, A Harris, CE Kumar, AR Zheng, Y Williams, DA Mulloy, JC AF Mizukawa, Benjamin Wei, Junping Shrestha, Mahesh Wunderlich, Mark Chou, Fu-Sheng Griesinger, Andrea Harris, Chad E. Kumar, Ashish R. Zheng, Yi Williams, David A. Mulloy, James C. TI Inhibition of Rac GTPase signaling and downstream prosurvival Bcl-2 proteins as combination targeted therapy in MLL-AF9 leukemia SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; GUANOSINE TRIPHOSPHATASES REPRESENT; ACUTE MYELOGENOUS LEUKEMIA; TRANSCRIPTIONAL ELONGATION; FAMILY PROTEINS; RHO GTPASES; DNA-DAMAGE; STEM-CELLS; MICE; FLT3 AB The Rac family of small Rho GTPases coordinates diverse cellular functions in hematopoietic cells including adhesion, migration, cytoskeleton rearrangements, gene transcription, proliferation, and survival. The integrity of Rac signaling has also been found to critically regulate cellular functions in the initiation and maintenance of hematopoietic malignancies. Using an in vivo gene targeting approach, we demonstrate that Rac2, but not Rac1, is critical to the initiation of acute myeloid leukemia in a retroviral expression model of MLL-AF9 leukemogenesis. However, loss of either Rac1 or Rac2 is sufficient to impair survival and growth of the transformed MLL-AF9 leukemia. Rac2 is known to positively regulate expression of Bcl-2 family proteins toward a prosurvival balance. We demonstrate that disruption of downstream survival signaling through antiapoptotic Bcl-2 proteins is implicated in mediating the effects of Rac2 deficiency in MLL-AF9 leukemia. Indeed, over-expression of Bcl-xL is able to rescue the effects of Rac2 deficiency and MLL-AF9 cells are exquisitely sensitive to direct inhibition of Bcl-2 family proteins by the BH3-mimetic, ABT-737. Furthermore, concurrent exposure to NSC23766, a small-molecule inhibitor of Rac activation, increases the apoptotic effect of ABT-737, indicating the Rac/Bcl-2 survival pathway may be targeted synergistically. (Blood. 2011;118(19):5235-5245) C1 [Wei, Junping; Shrestha, Mahesh; Wunderlich, Mark; Chou, Fu-Sheng; Griesinger, Andrea; Zheng, Yi; Mulloy, James C.] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA. [Mizukawa, Benjamin] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Div Oncol, Cincinnati, OH 45229 USA. [Harris, Chad E.; Williams, David A.] Harvard Univ, Div Hematol Oncol, Sch Med, Boston, MA 02115 USA. [Harris, Chad E.; Williams, David A.] Harvard Univ, Harvard Stem Cell Inst, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA. [Harris, Chad E.; Williams, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kumar, Ashish R.] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Div Bone Marrow Transplantat & Immunodeficiency, Cincinnati, OH 45229 USA. RP Mulloy, JC (reprint author), Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Div Expt Hematol & Canc Biol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM james.mulloy@cchmc.org RI Zheng, Yi/J-7235-2015 OI Zheng, Yi/0000-0001-7089-6074 FU National Institutes of Health/NICHD [K12-HD000850]; National Institutes of Health [K08-CA12291, DK62757, CA140518]; United States Public Health Service [MO1 RR 08 084]; National Center for Research Resources, National Institutes of Health, a Center of Excellence in Molecular Hematology [DK090971]; Gabrielle's Angel Foundation for Cancer Research FX B.M. is a Fellow of the Pediatric Scientist Development Program (PSDP). J.C.M. is a Leukemia & Lymphoma Society Scholar. This work was supported by National Institutes of Health/NICHD grant K12-HD000850 (B.M.), a Cancer Free Kids award (B.M.), ASH Scholar Award (J.W.), National Institutes of Health grants K08-CA12291 (A.R.K.), DK62757 (D.A.W.), and CA140518 (J.C.M.), United States Public Health Service grant MO1 RR 08 084, General Clinical Research Centers Program, National Center for Research Resources, National Institutes of Health, a Center of Excellence in Molecular Hematology P30 award (DK090971), and Gabrielle's Angel Foundation for Cancer Research (J.C.M.). NR 49 TC 21 Z9 21 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 10 PY 2011 VL 118 IS 19 BP 5235 EP 5245 DI 10.1182/blood-2011-04-351817 PG 11 WC Hematology SC Hematology GA 845ZN UT WOS:000296867100025 PM 21940819 ER PT J AU von Korff, M Katon, WJ Lin, EHB Ciechanowski, P Peterson, D Ludman, EJ Young, B Rutter, CM AF von Korff, Michael Katon, Wayne J. Lin, Elizabeth H. B. Ciechanowski, Paul Peterson, Do Ludman, Evette J. Young, Bessie Rutter, Carolyn M. TI Functional outcomes of multi-condition collaborative care and successful ageing: results of randomised trial SO BRITISH MEDICAL JOURNAL LA English DT Article ID QUALITY-OF-LIFE; CORONARY-HEART-DISEASE; MAJOR DEPRESSION; HEALTH-CARE; DISABILITY; MANAGEMENT; THERAPY; ANTIDEPRESSANT; COMPRESSION; VALIDATION AB Objective To evaluate the effectiveness of integrated care for chronic physical diseases and depression in reducing disability and improving quality of life. Design A randomised controlled trial of multi-condition collaborative care for depression and poorly controlled diabetes and/or risk factors for coronary heart disease compared with usual care among middle aged and elderly people Setting Fourteen primary care clinics in Seattle, Washington. Participants Patients with diabetes or coronary heart disease, or both, and blood pressure above 140/90 mm Hg, low density lipoprotein concentration >3.37 mmol/L, or glycated haemoglobin 8.5% or higher, and PHQ-9 depression scores of >= 10. Intervention A 12 month intervention to improve depression, glycaemic control, blood pressure, and lipid control by integrating a "treat to target" programme for diabetes and risk factors for coronary heart disease with collaborative care for depression. The intervention combined self management support, monitoring of disease control, and pharmacotherapy to control depression, hyperglycaemia, hypertension, and hyperlipidaemia. Main outcome measures Social role disability (Sheehan disability scale), global quality of life rating, and World Health Organization disability assessment schedule (WHODAS-2) scales to measure disabilities in activities of daily living (mobility, self care, household maintenance). Results Of 214 patients enrolled (106 intervention and 108 usual care), disability and quality of life measures were obtained for 97 intervention patients at six months (92%) and 92 at 12 months (87%), and for 96 usual care patients at six months (89%) and 92 at 12 months (85%). Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P=0.006) and global quality of life rating (0.7, 0.2 to 1.2; P=0.005) were significantly greater at six and 12 months in patients in the intervention group. There was a trend toward greater improvement in disabilities in activities of daily living (-1.5, -3.3 to 0.4; P=0.10). Conclusions Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life. C1 [von Korff, Michael; Lin, Elizabeth H. B.; Peterson, Do; Ludman, Evette J.; Rutter, Carolyn M.] Grp Hlth Res Inst, Seattle, WA 98101 USA. [Katon, Wayne J.; Ciechanowski, Paul] Univ Washington, Dept Psychiat & Behav Sci, Sch Med, Seattle, WA 98195 USA. [Young, Bessie] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Sch Med, Seattle, WA 98195 USA. [Young, Bessie] Univ Washington, Div Nephrol, Sch Med, Dept Med, Seattle, WA 98195 USA. [Rutter, Carolyn M.] Univ Washington, Dept Biostat, Sch Publ Hlth, Seattle, WA 98195 USA. RP von Korff, M (reprint author), Grp Hlth Res Inst, 1730 Minor Ave, Seattle, WA 98101 USA. EM vonkorff.m@ghc.org FU Group Health; National Institute of Mental Health Services Division, Bethesda, MD [MH041739, MH069741] FX The TEAMcare study would not have been possible without the support and participation of Group Health patients, primary care physicians, consultants, and leaders. We also acknowledge efforts and expertise by Tara Beatty, Malia Oliver, Sue Ruedebusch, Diana Griffith, and Sandy Randles. We also thank Michelle Wong, R James Dudl, and Kaiser Permanente Care Management Institute for providing the treat to target diabetes guidelines that we adapted. The content is solely the responsibility of the authors and does not necessarily represent the official views of the organisations that employ them.; This study was supported by grants MH041739 and MH069741 from the National Institute of Mental Health Services Division, Bethesda, MD (WJK) and by institutional support from Group Health Cooperative. The sponsors of this research had no influence over the conduct of the study, the analyses of study data, or the content of this paper. NR 41 TC 26 Z9 26 U1 2 U2 13 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD NOV 10 PY 2011 VL 343 AR d6612 DI 10.1136/bmj.d6612 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 848NT UT WOS:000297059000003 PM 22074851 ER PT J AU Mroz, EA Forastiere, AA Rocco, JW AF Mroz, Edmund A. Forastiere, Arlene A. Rocco, James W. TI Implications of the Oropharyngeal Cancer Epidemic SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS; NECK-CANCER; CONCURRENT CHEMORADIATION; HEAD; SURVIVAL; HPV; P16; PROGNOSIS; THERAPY C1 [Mroz, Edmund A.; Rocco, James W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Forastiere, Arlene A.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Rocco, James W.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Mroz, EA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. FU NIDCR NIH HHS [R01 DE022087] NR 27 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2011 VL 29 IS 32 BP 4222 EP 4223 DI 10.1200/JCO.2011.37.8893 PG 2 WC Oncology SC Oncology GA 845BJ UT WOS:000296797500009 PM 21969506 ER PT J AU Domchek, SM Mitchell, G Lindeman, GJ Tung, NM Balmana, J Isakoff, SJ Schmutzler, R Audeh, MW Loman, N Scott, C Friedlander, M Kaufman, B Garber, JE Tutt, A Robson, ME AF Domchek, Susan M. Mitchell, Gillian Lindeman, Geoffrey J. Tung, Nadine M. Balmana, Judith Isakoff, Steven J. Schmutzler, Rita Audeh, M. William Loman, Niklas Scott, Clare Friedlander, Michael Kaufman, Bella Garber, Judy E. Tutt, Andrew Robson, Mark E. TI Challenges to the Development of New Agents for Molecularly Defined Patient Subsets: Lessons From BRCA1/2-Associated Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID POLY(ADP-RIBOSE) POLYMERASE; MUTATION CARRIERS; INHIBITION; REPAIR; TUMORS C1 [Domchek, Susan M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Mitchell, Gillian] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Lindeman, Geoffrey J.; Scott, Clare] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. [Lindeman, Geoffrey J.; Scott, Clare] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Tung, Nadine M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Balmana, Judith] Vall dHebron Univ Hosp, Barcelona, Spain. [Isakoff, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schmutzler, Rita] Univ Cologne, Cologne, Germany. [Audeh, M. William] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Loman, Niklas] Skane Univ Hosp, Malmo, Sweden. [Friedlander, Michael] Prince Wales Canc Ctr, Sydney, NSW, Australia. [Kaufman, Bella] Chaim Sheba Med Ctr, Tel Aviv, Israel. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tutt, Andrew] Guys Hosp, Kings Hlth Partners Acad Hlth Sci Ctr, London SE1 9RT, England. [Robson, Mark E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Domchek, SM (reprint author), Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RI friedlander, michael/G-3490-2013; OI friedlander, michael/0000-0002-6488-0604; Robson, Mark/0000-0002-3109-1692 NR 14 TC 10 Z9 10 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2011 VL 29 IS 32 BP 4224 EP 4226 DI 10.1200/JCO.2011.36.8134 PG 3 WC Oncology SC Oncology GA 845BJ UT WOS:000296797500010 PM 21931031 ER PT J AU Richardson, PG Wolf, J Jakubowiak, A Zonder, J Lonial, S Irwin, D Densmore, J Krishnan, A Raje, N Bar, M Martin, T Schlossman, R Ghobrial, IM Munshi, N Laubach, J Allerton, J Hideshima, T Colson, K Poradosu, E Gardner, L Sportelli, P Anderson, KC AF Richardson, Paul G. Wolf, Jeff Jakubowiak, Andrzej Zonder, Jeff Lonial, Sagar Irwin, David Densmore, John Krishnan, Amrita Raje, Noopur Bar, Michael Martin, Tom Schlossman, Robert Ghobrial, Irene M. Munshi, Nikhil Laubach, Jacob Allerton, Jeff Hideshima, Teru Colson, Kathleen Poradosu, Enrique Gardner, Lesa Sportelli, Peter Anderson, Kenneth C. TI Perifosine Plus Bortezomib and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma Previously Treated With Bortezomib: Results of a Multicenter Phase I/II Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EXTENDED FOLLOW-UP; APEX TRIAL; PERIPHERAL NEUROPATHY; CLINICAL BENEFIT; COMBINATION; TANESPIMYCIN; VORINOSTAT; THERAPIES; SAFETY; REVERSIBILITY AB Purpose Novel agents have improved patient outcome in relapsed or relapsed/refractory multiple myeloma (MM). Preclinical data show that the novel signal transduction modulator, perifosine, enhances the cytotoxicity of dexamethasone and bortezomib. Clinical data suggest that perifosine in combination with dexamethasone has activity in relapsed or relapsed/refractory MM. Patients and Methods In a phase I/II study, perifosine in combination with bortezomib with or without dexamethasone was prospectively evaluated in 84 patients with relapsed or relapsed/refractory MM. All were heavily pretreated and bortezomib exposed; 73% were refractory to bortezomib, and 51% were refractory to bortezomib and dexamethasone. The dose selected for the phase II study was perifosine 50 mg/d plus bortezomib 1.3 mg/m(2), with the addition of low-dose dexamethasone at 20 mg if progression occurred on perifosine plus bortezomib alone. Results An overall response rate (ORR; defined as minimal response or better) of 41% was demonstrated with this combination in 73 evaluable patients, including an ORR of 65% in bortezomib-relapsed patients and 32% in bortezomib-refractory patients. Therapy was generally well tolerated; toxicities, including gastrointestinal adverse effects and fatigue, proved manageable. No treatment-related mortality was seen. Median progression-free survival was 6.4 months, with a median overall survival of 25 months (22.5 months in bortezomib-refractory patients). Conclusion Perifosine-bortezomib +/- dexamethasone demonstrated encouraging activity in heavily pretreated bortezomib-exposed patients with advanced MM. A phase III trial is underway comparing perifosine-bortezomib plus dexamethasone with bortezomib-dexamethasone in patients with relapsed/refractory MM previously treated with bortezomib. J Clin Oncol 29: 4243-4249. (C) 2011 by American Society of Clinical Oncology C1 [Richardson, Paul G.; Schlossman, Robert; Ghobrial, Irene M.; Munshi, Nikhil; Laubach, Jacob; Hideshima, Teru; Colson, Kathleen; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Raje, Noopur] Massachusetts Gen Canc Ctr, Boston, MA USA. [Wolf, Jeff; Martin, Tom] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Irwin, David] Alta Bates Canc Ctr, Berkeley, CA USA. [Krishnan, Amrita] City Hope Natl Med Ctr, Duarte, CA USA. [Jakubowiak, Andrzej] Univ Michigan, Ann Arbor, MI 48109 USA. [Zonder, Jeff] Karmanos Canc Ctr, Detroit, MI USA. [Lonial, Sagar] Winship Emory Canc Ctr, Atlanta, GA USA. [Densmore, John] Univ Virginia, Charlottesville, VA USA. [Bar, Michael] Bennett Canc Ctr, Stamford, CT USA. [Allerton, Jeff] Guthrie Canc Clin, Sayre, PA USA. [Poradosu, Enrique; Gardner, Lesa; Sportelli, Peter] Keryx Biopharmaceut, New York, NY USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 1B02, Boston, MA 02115 USA. EM paul_richardson@dfciharvard.edu FU Millennium Pharmaceuticals; Kerys Biopharmaceuticals; AstraZeneca; Acetylon Pharmaceuticals; Keryx Biopharmaceuticals, New York, NY FX Jeff Zonder, Millennium Pharmaceuticals; John Densmore, Kerys Biopharmaceuticals; Noopur Raje, AstraZeneca, Acetylon Pharmaceuticals; Irene M. Ghobrial, Millennium Pharmaceuticals; Supported by Keryx Biopharmaceuticals, New York, NY. NR 42 TC 73 Z9 75 U1 0 U2 2 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 NOV 10 PY 2011 VL 29 IS 32 BP 4243 EP 4249 DI 10.1200/JCO.2010.33.9788 PG 7 WC Oncology SC Oncology GA 845BJ UT WOS:000296797500013 PM 21990396 ER PT J AU Chen, AB Schrag, D AF Chen, Aileen B. Schrag, Deborah TI Computed Tomography-Based Simulation for Thoracic Radiation Therapy: Technical Advance or Clinical Evidence? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID CELL LUNG-CANCER; VARIABLES; SURVIVAL; OUTCOMES C1 [Chen, Aileen B.; Schrag, Deborah] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Chen, Aileen B.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Chen, AB (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2011 VL 29 IS 32 BP 4336 EP 4336 DI 10.1200/JCO.2011.38.2259 PG 1 WC Oncology SC Oncology GA 845BJ UT WOS:000296797500027 ER PT J AU Jha, AK Classen, DC AF Jha, Ashish K. Classen, David C. TI Getting Moving on Patient Safety - Harnessing Electronic Data for Safer Care SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. [Classen, David C.] Comp Sci Corp, Salt Lake City, UT USA. [Classen, David C.] Univ Utah, Salt Lake City, UT USA. RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. NR 5 TC 24 Z9 24 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 10 PY 2011 VL 365 IS 19 BP 1756 EP 1758 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 844QQ UT WOS:000296762800002 PM 22070474 ER PT J AU Cash, SS Larvie, M Dalmau, J AF Cash, Sydney S. Larvie, Mykol Dalmau, Josep TI Case 34-2011: A 75-Year-Old Man with Memory Loss and Partial Seizures SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TEMPORAL-LOBE EPILEPSY; POTASSIUM CHANNEL ANTIBODY; LIMBIC ENCEPHALITIS; LGI1; MUTATIONS C1 [Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Larvie, Mykol] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cash, Sydney S.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Larvie, Mykol] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Dalmau, Josep] Univ Penn, Dept Neurol, Div Neurooncol, Hosp Univ Penn, Philadelphia, PA 19104 USA. RP Cash, SS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. OI Dalmau, Josep/0000-0001-5856-2813 NR 19 TC 10 Z9 10 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 10 PY 2011 VL 365 IS 19 BP 1825 EP 1833 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 844QQ UT WOS:000296762800013 PM 22070480 ER PT J AU Abrams, JL Ecker, JL Barth, WH AF Abrams, Joshua L. Ecker, Jeffrey L. Barth, William H. TI Case 23-2011-Legal Considerations SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Abrams, Joshua L.; Ecker, Jeffrey L.; Barth, William H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Abrams, JL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 10 PY 2011 VL 365 IS 19 BP 1846 EP 1847 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 844QQ UT WOS:000296762800029 PM 22070495 ER PT J AU Wu, YN Johnson, SW AF Wu, Y. -N. Johnson, S. W. TI DOPAMINE OXIDATION FACILITATES ROTENONE-DEPENDENT POTENTIATION OF N-METHYL-D-ASPARTATE CURRENTS IN RAT SUBSTANTIA NIGRA DOPAMINE NEURONS SO NEUROSCIENCE LA English DT Article DE reactive oxygen species; rotenone; N-methyl-D-aspartate; monoamine oxidase; pargyline; reserpine ID PROTEIN-KINASE-C; MITOCHONDRIAL COMPLEX-I; PARKINSONS-DISEASE; NMDA-RECEPTOR; TYROSINE KINASE; DEPRENYL PROTECTS; RAPID DEVELOPMENT; TREATED RATS; PC12 CELLS; TOXICITY AB Rotenone is a mitochondrial poison that causes dopamine cell death and is used as a model of Parkinson's disease in rodents. Recently, we showed that rotenone augments currents evoked by N-methyl-D-aspartate (NMDA) by relieving voltage-dependent Mg(2+) block in rat substantia nigra compacta (SNC) dopamine neurons. Because rotenone is well known to generate reactive oxygen species (ROS), we conducted the present experiments to evaluate the role of ROS in mediating the effect of rotenone on NMDA current augmentation. Using patch pipettes to record whole-cell currents from SNC neurons in slices of rat brain, we found that the ability of rotenone (100 nM) to increase NMDA (3-30 mu M) current was antagonized by the antioxidant agent N-acetylcysteine (1 mM). In contrast, mercaptosuccinate (1 mM), which blocks glutathione peroxidase and raises tissue levels of H(2)O(2), mimicked rotenone by augmenting inward currents evoked by NMDA. Because oxidation of dopamine can also generate ROS, we explored the role of dopamine on this action of rotenone. We prepared dopamine-depleted midbrain slices from rats that had been pretreated with reserpine (5 mg/kg ip) and alpha-methyl-para-tyrosine (AMPT, 250 mg/kg ip). Dopamine depletion blocked the ability of rotenone (100 nM) to increase inward current evoked by NMDA (30 mu M). Rotenone-dependent augmentation of NMDA current was also blocked by the monoamine oxidase inhibitor pargyline (100 mu M) in slices prepared from normal rats. In contrast, the dopamine precursor levodopa potentiated the action of rotenone on NMDA current. These results suggest that ROS and/or dopamine oxidation products mediate the ability of rotenone to potentiate NMDA currents. Because excessive NMDA receptor stimulation can produce excitotoxicity, our results suggest that oxidative metabolism of dopamine might facilitate the neurotoxicity of rotenone. Published by Elsevier Ltd on behalf of IBRO. C1 [Wu, Y. -N.; Johnson, S. W.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Johnson, S. W.] Portland VA Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. EM johnsost@ohsu.edu FU Veterans Affairs Merit Review [0383]; Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center FX This research was supported by Veterans Affairs Merit Review grant 0383 and by the Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center. NR 53 TC 11 Z9 11 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD NOV 10 PY 2011 VL 195 BP 138 EP 144 DI 10.1016/j.neuroscience.2011.08.041 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 833EF UT WOS:000295863900014 PM 21884756 ER PT J AU Hill-Burns, EM Factor, SA Zabetian, CP Thomson, G Payami, H AF Hill-Burns, Erin M. Factor, Stewart A. Zabetian, Cyrus P. Thomson, Glenys Payami, Haydeh TI Evidence for More than One Parkinson's Disease-Associated Variant within the HLA Region SO PLOS ONE LA English DT Article ID POPULATION; METAANALYSIS; HAPLOTYPES; IMPUTATION; GENETICS; SNCA AB Parkinson's disease (PD) was recently found to be associated with HLA in a genome-wide association study (GWAS). Followup GWAS's replicated the PD-HLA association but their top hits differ. Do the different hits tag the same locus or is there more than one PD-associated variant within HLA? We show that the top GWAS hits are not correlated with each other (0.00 <= r(2)<= 0.15). Using our GWAS (2000 cases, 1986 controls) we conducted step-wise conditional analysis on 107 SNPs with P, 10 23 for PD-association; 103 dropped-out, four remained significant. Each SNP, when conditioned on the other three, yielded P(SNP1) = 5610 24, P(SNP2) = 5610 24, P(SNP3) = 4610 23 and P(SNP4) = 0.025. The four SNPs were not correlated (0.01 <= r(2)<= 0.20). Haplotype analysis (excluding rare SNP2) revealed increasing PD risk with increasing risk alleles from OR = 1.27, P = 5610 23 for one risk allele to OR = 1.65, P = 4610 28 for three. Using additional 843 cases and 856 controls we replicated the independent effects of SNP1 (P(conditioned-on-SNP4) = 0.04) and SNP4 (P(conditioned-on-SNP1) = 0.04); SNP2 and SNP3 could not be replicated. In pooled GWAS and replication, SNP1 had OR(conditioned-on-SNP4) = 1.23, P(conditioned-on-SNP4) = 6610 27; SNP4 had OR(conditioned-on-SNP1) = 1.18, P(conditioned-on-SNP1) = 3610 23; and the haplotype with both risk alleles had OR = 1.48, P = 2x10(-12). Genotypic OR increased with the number of risk alleles an individual possessed up to OR = 1.94, P = 2610 211 for individuals who were homozygous for the risk allele at both SNP1 and SNP4. SNP1 is a variant in HLA-DRA and is associated with HLA-DRA, DRB5 and DQA2 gene expression. SNP4 is correlated (r(2) = 0.95) with variants that are associated with HLA-DQA2 expression, and with the top HLA SNP from the IPDGC GWAS (r(2) = 0.60). Our findings suggest more than one PD-HLA association; either different alleles of the same gene, or separate loci. C1 [Hill-Burns, Erin M.; Payami, Haydeh] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Zabetian, Cyrus P.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Thomson, Glenys] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. RP Hill-Burns, EM (reprint author), New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. EM hpayami@wadsworth.org OI Zabetian, Cyrus/0000-0002-7739-4306 FU National Institute of Neurological Disorders And Stroke (NINDS) [R01 NS36960, R01 NS067469]; Edmond J. Safra Michael J. Fox Foundation Global Genetic Consortium Initiative; Department of Veterans Affairs [I01BX000531]; Close to a Cure Foundation: A Fund for Parkinson's Research of Foundation for the Carolinas; National Institute of Allergy and Infectious Disease [AI40076] FX Study was supported by grants from the National Institute of Neurological Disorders And Stroke (NINDS R01 NS36960 and R01 NS067469 to HP), the Edmond J. Safra Michael J. Fox Foundation Global Genetic Consortium Initiative (HP), the Department of Veterans Affairs ('I01BX000531 to CZ), The Close to a Cure Foundation: A Fund for Parkinson's Research of Foundation for the Carolinas (SF), and the National Institute of Allergy and Infectious Disease (AI40076, GT). Funding support for the replication dataset was provided by the National Institute of Neurological Disorders and Stroke (Foroud/Myers, PI). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 20 Z9 20 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 9 PY 2011 VL 6 IS 11 AR e27109 DI 10.1371/journal.pone.0027109 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 852II UT WOS:000297350800027 PM 22096524 ER PT J AU Li, JF Bush, J Xiong, Y Li, L McCormack, M AF Li, Jian-Feng Bush, Jenifer Xiong, Yan Li, Lei McCormack, Matthew TI Large-Scale Protein-Protein Interaction Analysis in Arabidopsis Mesophyll Protoplasts by Split Firefly Luciferase Complementation SO PLOS ONE LA English DT Article ID AUXIN RESPONSE FACTORS; FRAGMENT-ASSISTED COMPLEMENTATION; LATERAL ROOT DEVELOPMENT; SIGNAL-TRANSDUCTION; INTERACTION NETWORK; REGULATED PROTEIN; CIRCADIAN CLOCK; GENE-EXPRESSION; AUX/IAA PROTEIN; LIVING SUBJECTS AB Protein-protein interactions (PPIs) constitute the regulatory network that coordinates diverse cellular functions. There are growing needs in plant research for creating protein interaction maps behind complex cellular processes and at a systems biology level. However, only a few approaches have been successfully used for large-scale surveys of PPIs in plants, each having advantages and disadvantages. Here we present split firefly luciferase complementation (SFLC) as a highly sensitive and noninvasive technique for in planta PPI investigation. In this assay, the separate halves of a firefly luciferase can come into close proximity and transiently restore its catalytic activity only when their fusion partners, namely the two proteins of interest, interact with each other. This assay was conferred with quantitativeness and high throughput potential when the Arabidopsis mesophyll protoplast system and a microplate luminometer were employed for protein expression and luciferase measurement, respectively. Using the SFLC assay, we could monitor the dynamics of rapamycin-induced and ascomycin-disrupted interaction between Arabidopsis FRB and human FKBP proteins in a near real-time manner. As a proof of concept for large-scale PPI survey, we further applied the SFLC assay to testing 132 binary PPIs among 8 auxin response factors (ARFs) and 12 Aux/IAA proteins from Arabidopsis. Our results demonstrated that the SFLC assay is ideal for in vivo quantitative PPI analysis in plant cells and is particularly powerful for large-scale binary PPI screens. C1 [Li, Jian-Feng; Xiong, Yan; Li, Lei; McCormack, Matthew] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Li, Jian-Feng; Bush, Jenifer; Xiong, Yan; Li, Lei; McCormack, Matthew] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Li, JF (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM jli@molbio.mgh.harvard.edu RI Li, Lei/F-9826-2015 FU Massachusetts General Hospital; National Institutes of Health [GM070567] FX This work was supported by Massachusetts General Hospital postdoctoral fellowship for medical discovery awarded to Dr. Li, and the National Institutes of Health grant GM070567 to Dr. Sheen (Massachusetts General Hospital, United States of America). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 23 Z9 36 U1 1 U2 19 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 9 PY 2011 VL 6 IS 11 AR e27364 DI 10.1371/journal.pone.0027364 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 852II UT WOS:000297350800050 PM 22096563 ER PT J AU Fainzilber, M Budnik, V Segal, RA Kreutz, MR AF Fainzilber, Mike Budnik, Vivian Segal, Rosalind A. Kreutz, Michael R. TI From Synapse to Nucleus and Back Again-Communication over Distance within Neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article ID SURVIVAL RESPONSE; PROTEIN-SYNTHESIS; BCL-W; NERVE; PLASTICITY; IMPORT; TRANSLOCATION; TRANSCRIPTION; TRANSLATION; TRANSPORT AB How do neurons integrate intracellular communication from synapse to nucleus and back? Here we briefly summarize aspects of this topic covered by a symposium at Neuroscience 2011. A rich repertoire of signaling mechanisms link both dendritic terminals and axon tips with neuronal soma and nucleus, using motor-dependent transport machineries to traverse the long intracellular distances along neuronal processes. Activation mechanisms at terminals include localized translation of dendritic or axonal RNA, proteolytic cleavage of receptors or second messengers, and differential phosphorylation of signaling moieties. Signaling complexes may be transported in endosomes, or as non-endosomal complexes associated with importins and dynein. Anterograde transport of RNA granules from the soma to neuronal processes, coupled with retrograde transport of proteins translated locally at terminals or within processes, may fuel ongoing bidirectional communication between soma and synapse to modulate synaptic plasticity as well as neuronal growth and survival decisions. C1 [Fainzilber, Mike] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. [Budnik, Vivian] Univ Massachusetts, Sch Med, Dept Neurobiol, Worcester, MA 01605 USA. [Segal, Rosalind A.] Dana Farber Canc Inst, Dept Pediat Oncol & Canc Biol, Boston, MA 02215 USA. [Segal, Rosalind A.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02215 USA. [Kreutz, Michael R.] Leibniz Inst Neurobiol, Neuroplast Grp, D-39118 Magdeburg, Germany. RP Fainzilber, M (reprint author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. EM mike.fainzilber@weizmann.ac.il OI Fainzilber, Mike/0000-0001-8173-8557 FU Israel Science Foundation; German-Israeli Foundation; Minerva Foundation; International Foundation for Research in Paraplegia; Christopher and Dana Reeve Foundation; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; NIH [R01 NS063228, R01 MH091662, R01 NS050674]; Center for Brain and Behavior Sciences Magdeburg; Deutsche Forschungsgemeinschaft; Bundesministerium fur Bildung und Forschung; DZNE Magdeburg; Deutsche-Israelische Projektkooperation; Leibniz Foundation (Pakt fur Forschung); Schram Foundation FX We gratefully acknowledge grant support as follows: M.F.-from the Israel Science Foundation, the German-Israeli Foundation, the Minerva Foundation, the International Foundation for Research in Paraplegia, the Christopher and Dana Reeve Foundation, and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; V.B.-NIH Grant R01 NS063228; R.A.S.-NIH Grants R01 MH091662 and R01 NS050674; M.R.K.-Center for Brain and Behavior Sciences Magdeburg, Deutsche Forschungsgemeinschaft, Bundesministerium fur Bildung und Forschung, DZNE Magdeburg, the Deutsche-Israelische Projektkooperation, Leibniz Foundation (Pakt fur Forschung), and Schram Foundation. NR 34 TC 13 Z9 13 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 9 PY 2011 VL 31 IS 45 BP 16045 EP 16048 DI 10.1523/JNEUROSCI.4006-11.2011 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 845CE UT WOS:000296799700001 PM 22072654 ER PT J AU Konno, T Hata, S Hamada, Y Horikoshi-Sakuraba, Y Nakaya, T Saito, Y Yamamoto, T Yamamoto, T Maeda, M Ikeuchi, T Gandy, S Akatsu, H Suzuki, T AF Konno, Tomoko Hata, Saori Hamada, Yukiko Horikoshi-Sakuraba, Yuko Nakaya, Tadashi Saito, Yuhki Yamamoto, Tohru Yamamoto, Takayuki Maeda, Masahiro Ikeuchi, Takeshi Gandy, Sam Akatsu, Hiroyasu Suzuki, Toshiharu CA Japanese Alzheimers Dis TI Coordinated increase of gamma-secretase reaction products in the plasma of some female Japanese sporadic Alzheimer's disease patients: quantitative analysis of p3-Alc alpha with a new ELISA system SO MOLECULAR NEURODEGENERATION LA English DT Article ID TRAUMATIC BRAIN-INJURY; AMYLOID-BETA; APOLIPOPROTEIN-E; ASSOCIATION; ESTROGEN; PEPTIDE; GENE; NEURODEGENERATION; DEGRADATION; METABOLISM AB Background: Aggregatable amyloid beta-peptide (A beta) and non-aggregatable p3-Alc alpha are metabolic products of the gamma-secretase cleavage of amyloid beta-protein precursor (APP) and Alcadein alpha (Alc alpha), respectively. Familial AD (FAD)-linked mutations in the presenilin 1 or 2 (PS1 or PS2) component of gamma-secretase can cause alternative intramembranous processing of APP and Alc alpha, leading to a coordinated generation of variants of both A beta and p3-Alc alpha. Variant Alc alpha peptides have been observed in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment and sporadic Alzheimer's disease (AD). Since, like APP, Alc alpha is largely expressed in brain, one might predict that alternative processing of Alca would be reflected in body fluids of some AD patients. These patients with misprocessing of multiple gamma-secretase substrates might define an endophenotype of p3-Alc alpha, in whom AD is due either to dysfunction of gamma-secretase or to a disorder of the clearance of hydrophobic peptides such as those derived from transmembrane domains. Results: We developed a simple procedure for extraction of p3-Alc alpha from plasma and for analyzing this extract in a sensitive, p3-Alc alpha-specific sandwich enzyme-linked immunosorbent assay (ELISA) system. Plasma p3-Alca levels and A beta 40 levels were examined in sporadic AD subjects from two independent Japanese cohorts. In some of these patients, levels of plasma p3-Alc alpha were significantly higher, and were accompanied by parallel changes in A beta 40 levels. This AD-related difference was more marked in female subjects, but this phenomenon was not observed in subjects with frontotemporal lobar degeneration (FTLD). Conclusion: Reagents and procedures have been established that enable extraction of p3-Alc alpha from plasma and for quantification of plasma p3-Alc alpha levels by ELISA. Some populations of AD subjects apparently show increased levels of both p3-Alc alpha and A beta 40. Quantification of p3-Alc alpha level may be useful as a readily accessible biomarker for a population of sporadic AD patients in which disease pathogenesis is associated with either dysfunction of gamma-secretase or with a disorder of the clearance of transmembrane domain-derived peptides. C1 [Konno, Tomoko; Hata, Saori; Nakaya, Tadashi; Saito, Yuhki; Yamamoto, Tohru; Suzuki, Toshiharu] Hokkaido Univ, Grad Sch Pharmaceut Sci, Neurosci Lab, Sapporo, Hokkaido 0600812, Japan. [Hamada, Yukiko; Horikoshi-Sakuraba, Yuko; Maeda, Masahiro] Immunobiol Labs Co Ltd IBL, Fujioka 3750005, Japan. [Yamamoto, Takayuki; Akatsu, Hiroyasu] Fukushimura Hosp, Choju Med Inst, Toyohashi, Aichi 4418124, Japan. [Ikeuchi, Takeshi] Niigata Univ, Brain Res Inst, Dept Mol Neurosci, Niigata 9518585, Japan. [Gandy, Sam] Alzheimers Dis Res Ctr, Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Gandy, Sam] Alzheimers Dis Res Ctr, Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Gandy, Sam] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. RP Suzuki, T (reprint author), Hokkaido Univ, Grad Sch Pharmaceut Sci, Neurosci Lab, Sapporo, Hokkaido 0600812, Japan. EM tsuzuki@pharm.hokudai.ac.jp RI Hata, Saori /A-3829-2012; Yamamoto, Tohru/A-3801-2012; Suzuki, Toshiharu/B-5342-2013 OI Yamamoto, Tohru/0000-0002-1652-0233; FU Ministry of Education, Culture, Sports, Science and Technology (MEXT); Ministry of Health, Labor and Welfare (MHLW); New Energy and Industrial Technology Development Organization (NEDO) in Japan; NIA Alzheimer's Disease Research Center [P50 05138] FX This work was supported in part by Grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), a grant from the Ministry of Health, Labor and Welfare (MHLW), and a grant from the New Energy and Industrial Technology Development Organization (NEDO) in Japan. S.G. was supported by the NIA Alzheimer's Disease Research Center grant P50 05138 to Mary Sano. NR 32 TC 5 Z9 5 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1326 J9 MOL NEURODEGENER JI Mol. Neurodegener. PD NOV 8 PY 2011 VL 6 AR 76 DI 10.1186/1750-1326-6-76 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 864NT UT WOS:000298247600001 PM 22067061 ER PT J AU Singh, T Sharma, SD Katiyar, SK AF Singh, Tripti Sharma, Som D. Katiyar, Santosh K. TI Grape Proanthocyanidins Induce Apoptosis by Loss of Mitochondrial Membrane Potential of Human Non-Small Cell Lung Cancer Cells In Vitro and In Vivo SO PLOS ONE LA English DT Article ID SKH-1 HAIRLESS MICE; DEPENDENT KINASES; ANTICANCER DRUGS; CARCINOMA-CELLS; CYCLE CONTROL; BCL-2 FAMILY; DEATH; INHIBITORS; PROTEIN; GROWTH AB Lung cancer remains the leading cause of cancer-related deaths worldwide, and non-small cell lung cancer (NSCLC) represents approximately 80% of total lung cancer cases. The use of non-toxic dietary phytochemicals can be considered as a chemotherapeutic strategy for the management of the NSCLC. Here, we report that grape seed proanthocyanidins (GSPs) induce apoptosis of NSCLC cells, A549 and H1299, in vitro which is mediated through increased expression of pro-apoptotic protein Bax, decreased expression of anti-apoptotic proteins Bcl2 and Bcl-xl, disruption of mitochondrial membrane potential, and activation of caspases 9, 3 and poly (ADP-ribose) polymerase (PARP). Pre-treatment of A549 and H1299 cells with the caspase-3 inhibitor (z-DEVD-fmk) significantly blocked the GSPs-induced apoptosis of these cells confirmed that GSPs-induced apoptosis is mediated through activation of caspases-3. Treatments of A549 and H1299 cells with GSPs resulted in an increase in G1 arrest. G0/G1 phase of the cell cycle is known to be controlled by cyclin dependent kinases (Cdk), cyclin-dependent kinase inhibitors (Cdki) and cyclins. Our western blot analyses showed that GSPs-induced G1 cell cycle arrest was mediated through the increased expression of Cdki proteins (Cip1/p21 and Kip1/p27), and a simultaneous decrease in the levels of Cdk2, Cdk4, Cdk6 and cyclins. Further, administration of 50, 100 or 200 mg GSPs/kg body weight of mice by oral gavage (5 d/week) markedly inhibited the growth of s.c. A549 and H1299 lung tumor xenografts in athymic nude mice, which was associated with the induction of apoptotic cell death, increased expression of Bax, reduced expression of anti-apoptotic proteins and activation of caspase-3 in tumor xenograft cells. Based on the data obtained in animal study, human equivalent dose of GSPs was calculated, which seems affordable and attainable. Together, these results suggest that GSPs may represent a potential therapeutic agent for the non-small cell lung cancer. C1 [Singh, Tripti; Sharma, Som D.; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Katiyar, Santosh K.] Univ Alabama, Nutr Obes Res Ctr, Birmingham, AL USA. [Katiyar, Santosh K.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. RP Singh, T (reprint author), Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU Veterans Administration Merit Review Award FX This work was supported by funds from the Veterans Administration Merit Review Award (SKK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 34 Z9 37 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 8 PY 2011 VL 6 IS 11 AR e27444 DI 10.1371/journal.pone.0027444 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 852HZ UT WOS:000297349700046 PM 22087318 ER PT J AU Azadani, A Chitsaz, S Tseng, E Ge, L AF Azadani, Ali Chitsaz, Sam Tseng, Elaine Ge, Liang TI Finite Element Analysis of Transcatheter Aortic Valve Implantation: Impact of Oversizing on Stent and Leaflet Stresses SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 23rd Annual Transcatheter Cardiovascular Therapeutics (TCT) Symposium CY NOV 07-11, 2011 CL San Francisco, CA C1 [Azadani, Ali; Chitsaz, Sam; Tseng, Elaine; Ge, Liang] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Azadani, Ali; Chitsaz, Sam; Tseng, Elaine; Ge, Liang] San Francisco VA Med Ctr, San Francisco, CA USA. RI Chitsaz, Sam/C-4586-2008 NR 0 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 8 PY 2011 VL 58 IS 20 SU B BP B198 EP B198 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 846IZ UT WOS:000296891900736 ER PT J AU Chitsaz, S Jaussaud, N Meadows, A Wintermark, M Cambronero, N Azadani, AN Saloner, DA Chuter, TA Ge, L Tseng, EE AF Chitsaz, Sam Jaussaud, Nicolas Meadows, Alison Wintermark, Max Cambronero, Neil Azadani, Ali N. Saloner, David A. Chuter, Timothy A. Ge, Liang Tseng, Elaine E. TI Thoracic Endovascular Aortic Repair for Acute Type A Dissection: A Computational and Anatomic Analysis of Technical Limitations for Available Devices SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 23rd Annual Transcatheter Cardiovascular Therapeutics (TCT) Symposium CY NOV 07-11, 2011 CL San Francisco, CA C1 [Chitsaz, Sam; Jaussaud, Nicolas; Wintermark, Max; Cambronero, Neil; Azadani, Ali N.; Chuter, Timothy A.; Ge, Liang; Tseng, Elaine E.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Chitsaz, Sam; Jaussaud, Nicolas; Azadani, Ali N.; Saloner, David A.; Ge, Liang; Tseng, Elaine E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Meadows, Alison; Saloner, David A.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. RI Chitsaz, Sam/C-4586-2008 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 8 PY 2011 VL 58 IS 20 SU B BP B155 EP B155 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 846IZ UT WOS:000296891900575 ER PT J AU Dattilo, PB Tsai, TT Casserly, IP AF Dattilo, Philip B. Tsai, Thomas T. Casserly, Ivan P. TI Endovascular Therapy of Common Femoral Arterial Disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 23rd Annual Transcatheter Cardiovascular Therapeutics (TCT) Symposium CY NOV 07-11, 2011 CL San Francisco, CA C1 [Dattilo, Philip B.; Tsai, Thomas T.; Casserly, Ivan P.] Univ Colorado, Sch Med, Aurora, CO USA. [Tsai, Thomas T.; Casserly, Ivan P.] Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 8 PY 2011 VL 58 IS 20 SU B BP B157 EP B157 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 846IZ UT WOS:000296891900582 ER PT J AU Fleming, CP Tanaka, A Gardecki, JA Maurovich-Horvat, P Winger, WC Eckert, JE Hoffmann, T Bouma, BE Tearney, GJ AF Fleming, Christine P. Tanaka, Atsushi Gardecki, Joseph A. Maurovich-Horvat, Pal Winger, William C. Eckert, Jocelyn E. Hoffmann, Tido Bouma, Bren E. Tearney, Guillermo J. TI Classification of Atherosclerotic Plaques using Depth Resolved Spectral Analysis of Optical Frequency Domain Imaging Datasets SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 23rd Annual Transcatheter Cardiovascular Therapeutics (TCT) Symposium CY NOV 07-11, 2011 CL San Francisco, CA C1 [Fleming, Christine P.; Tanaka, Atsushi; Gardecki, Joseph A.; Winger, William C.; Eckert, Jocelyn E.; Bouma, Bren E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Maurovich-Horvat, Pal] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fleming, Christine P.; Tanaka, Atsushi; Gardecki, Joseph A.; Maurovich-Horvat, Pal; Winger, William C.; Hoffmann, Tido; Bouma, Bren E.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA USA. RI Hendon, Christine/F-8261-2016 OI Hendon, Christine/0000-0001-7318-1517 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 8 PY 2011 VL 58 IS 20 SU B BP B174 EP B174 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 846IZ UT WOS:000296891900648 ER PT J AU Kim, JS Afari, ME Ha, J Tellez, A Milewski, K Condin, G Cheng, YP Kaluza, GL Granada, JF AF Kim, Jung-Sun Afari, Maxwell E. Ha, Jinyoung Tellez, Armando Milewski, Krzysztof Condin, Gerard Cheng, Yanping Kaluza, Greg L. Granada, Juan F. TI Optical Characteristics of Neointimal Formation Correlate with Histological Markers of Stent Healing in a Porcine Model of Restenosis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 23rd Annual Transcatheter Cardiovascular Therapeutics (TCT) Symposium CY NOV 07-11, 2011 CL San Francisco, CA C1 [Kim, Jung-Sun; Afari, Maxwell E.; Tellez, Armando; Milewski, Krzysztof; Condin, Gerard; Cheng, Yanping; Kaluza, Greg L.; Granada, Juan F.] Skirball Ctr, Orangeburg, NY USA. [Ha, Jinyoung] Harvard Univ, Sch Med, Boston, MA USA. [Ha, Jinyoung] Massachusetts Gen Hosp, Wellman Ctr Photo Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 8 PY 2011 VL 58 IS 20 SU B BP B121 EP B121 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 846IZ UT WOS:000296891900446 ER PT J AU Maini, B O'Neill, W Dixon, S Palacios, I Schreiber, T Gregory, DA Scotti, DJ AF Maini, Brijeshwar O'Neill, William Dixon, Simon Palacios, Igor Schreiber, Theodore Gregory, David A. Scotti, D. J. TI Cost-effectiveness and Clinical Outcomes of Impella Hemodynamic Support Compared with Intra-Aortic Balloon Pump in High Risk Patients Receiving PCI: Results from the PROTECT II Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 23rd Annual Transcatheter Cardiovascular Therapeutics (TCT) Symposium CY NOV 07-11, 2011 CL San Francisco, CA C1 [Maini, Brijeshwar] PinnacleHlth Cardiovasc Inst, Wormleysburg, PA USA. [O'Neill, William] Univ Miami, Miami, FL USA. [Palacios, Igor] Beaumont Hosp, Royal Oak, MI USA. [Dixon, Simon] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schreiber, Theodore] Detroit Med Ctr, Detroit, MI USA. [Gregory, David A.; Scotti, D. J.] Presscott Associates Ltd, Avon, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 8 PY 2011 VL 58 IS 20 SU B BP B131 EP B132 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 846IZ UT WOS:000296891900485 ER PT J AU McCabe, JM Armstrong, EJ Hoffmayer, KS Bhave, P Stein, JC Kinlay, S Ganz, P AF McCabe, James M. Armstrong, Ehrin J. Hoffmayer, Kurt S. Bhave, Prashant Stein, John C. Kinlay, Scott Ganz, Peter TI Factors Associated with Belays in Primary PCI and Cardiac Catheterization Laboratory Activation for ST-Segment Elevation Myocardial Infarctions; A report from the Activate-SF registry SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 23rd Annual Transcatheter Cardiovascular Therapeutics (TCT) Symposium CY NOV 07-11, 2011 CL San Francisco, CA C1 [Stein, John C.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. [Kinlay, Scott] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Kinlay, Scott] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 8 PY 2011 VL 58 IS 20 SU B BP B21 EP B21 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 846IZ UT WOS:000296891900092 ER PT J AU Owens, CD Gasper, WJ Kim, JM Rapp, J Grenon, M Seward, K AF Owens, Christopher D. Gasper, Warren J. Kim, Ji Min Rapp, Joseph Grenon, Marlene Seward, Kirk TI Dexamethasone Infusion to the Adventitia to Enhance Clinical Efficacy after Femoropopliteal Revascularization: A First in Man Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 23rd Annual Transcatheter Cardiovascular Therapeutics (TCT) Symposium CY NOV 07-11, 2011 CL San Francisco, CA C1 [Owens, Christopher D.; Gasper, Warren J.; Kim, Ji Min; Rapp, Joseph; Grenon, Marlene] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Owens, Christopher D.; Gasper, Warren J.; Rapp, Joseph; Grenon, Marlene] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. [Seward, Kirk] Mercator MedSyst Inc, San Leandro, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 8 PY 2011 VL 58 IS 20 SU B BP B155 EP B155 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 846IZ UT WOS:000296891900574 ER PT J AU Xu, H Nguyen, KT Terada, LS Fuh, E Garcia, JA Brilakis, ES Bhatt, DL Banerjee, S AF Xu, Hao Kytai T Nguyen Terada, Lance S. Fuh, Eric Garcia, Joseph A. Brilakis, Emmanouil S. Bhatt, Deepak L. Banerjee, Subhash TI Response of Endothelial Progenitor Cells To Antiproliferative Drugs Currently Used in Drug Eluting Stents SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 23rd Annual Transcatheter Cardiovascular Therapeutics (TCT) Symposium CY NOV 07-11, 2011 CL San Francisco, CA C1 [Terada, Lance S.; Fuh, Eric; Garcia, Joseph A.; Brilakis, Emmanouil S.; Banerjee, Subhash] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Xu, Hao; Garcia, Joseph A.; Brilakis, Emmanouil S.; Banerjee, Subhash] VA N Texas Hlth Care Ctr, Dallas, TX USA. [Kytai T Nguyen] Univ Texas Arlington, Arlington, TX 76019 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 8 PY 2011 VL 58 IS 20 SU B BP B70 EP B71 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 846IZ UT WOS:000296891900267 ER PT J AU Kinlay, S AF Kinlay, Scott TI Changes in Stroke Epidemiology, Prevention, and Treatment SO CIRCULATION LA English DT Review DE stroke; epidemiology; risk factors; anticoagulation; atrial fibrillation; thrombolysis; stents; revascularization; clinical trials ID ATRIAL-FIBRILLATION; MYOCARDIAL-INFARCTION; ISCHEMIC-STROKE; BLOOD-PRESSURE; HEART-DISEASE; RISK; ENDARTERECTOMY; WARFARIN; METAANALYSIS; STENOSIS C1 [Kinlay, Scott] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Kinlay, Scott] Harvard Univ, Sch Med, Boston, MA USA. RP Kinlay, S (reprint author), VA Boston Healthcare Syst, Cardiac Catheterizat Lab & Vasc Med, Cardiovasc Div, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM scott.kinlay@va.gov FU CSRD Merit [1I01CX000440-01A1] FX Dr Kinlay is supported by a CSR&D Merit 1I01CX000440-01A1. NR 26 TC 26 Z9 28 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 8 PY 2011 VL 124 IS 19 BP E494 EP E496 DI 10.1161/CIRCULATIONAHA.111.069633 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 844SE UT WOS:000296766800002 PM 22064961 ER PT J AU Santagata, S Hu, R Lin, NU Mendillo, ML Collins, LC Hankinson, SE Schnitt, SJ Whitesell, L Tamimi, RM Lindquist, S Ince, TA AF Santagata, Sandro Hu, Rong Lin, Nancy U. Mendillo, Marc L. Collins, Laura C. Hankinson, Susan E. Schnitt, Stuart J. Whitesell, Luke Tamimi, Rulla M. Lindquist, Susan Ince, Tan A. TI High levels of nuclear heat-shock factor 1 (HSF1) are associated with poor prognosis in breast cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE heat-shock protein 90; signature; pathology; heat-shock response; immunohistochemistry ID TRANSCRIPTION FACTOR HSF1; ESTROGEN-RECEPTOR-ALPHA; NON-ONCOGENE ADDICTION; TANESPIMYCIN 17-AAG; PROTEIN 90; HSP90; GROWTH; PROGRESSION; ADENOCARCINOMA; TRANSFORMATION AB Heat-shock factor 1 (HSF1) is the master transcriptional regulator of the cellular response to heat and a wide variety of other stressors. We previously reported that HSF1 promotes the survival and proliferation of malignant cells. At this time, however, the clinical and prognostic significance of HSF1 in cancer is unknown. To address this issue breast cancer samples from 1,841 participants in the Nurses' Health Study were scored for levels of nuclear HSF1. Associations of HSF1 status with clinical parameters and survival outcomes were investigated by Kaplan-Meier analysis and Cox proportional hazard models. The associations were further delineated by Kaplan-Meier analysis using publicly available mRNA expression data. Our results show that nuclear HSF1 levels were elevated in similar to 80% of in situ and invasive breast carcinomas. In invasive carcinomas, HSF1 expression was associated with high histologic grade, larger tumor size, and nodal involvement at diagnosis (P < 0.0001). By using multivariate analysis to account for the effects of covariates, high HSF1 levels were found to be independently associated with increased mortality (hazards ratio: 1.62; 95% confidence interval: 1.21-2.17; P < 0.0013). This association was seen in the estrogen receptor (ER)-positive population (hazards ratio: 2.10; 95% confidence interval: 1.45-3.03; P < 0.0001). In public expression profiling data, high HSF1 mRNA levels were also associated with an increase in ER-positive breast cancer-specific mortality. We conclude that increased HSF1 is associated with reduced breast cancer survival. The findings indicate that HSF1 should be evaluated prospectively as an independent prognostic indicator in ER-positive breast cancer. HSF1 may ultimately be a useful therapeutic target in cancer. C1 [Hu, Rong; Hankinson, Susan E.; Tamimi, Rulla M.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Santagata, Sandro; Hu, Rong; Collins, Laura C.; Hankinson, Susan E.; Schnitt, Stuart J.; Tamimi, Rulla M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Santagata, Sandro; Mendillo, Marc L.; Whitesell, Luke; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Santagata, Sandro] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Hu, Rong; Hankinson, Susan E.; Tamimi, Rulla M.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Lin, Nancy U.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Collins, Laura C.; Schnitt, Stuart J.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. [Lindquist, Susan] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. [Ince, Tan A.] Univ Miami, Sch Med, Interdisciplinary Stem Cell Inst, Miami, FL 33136 USA. [Ince, Tan A.] Univ Miami, Sch Med, Braman Family Breast Canc Inst, Dept Pathol, Miami, FL 33136 USA. RP Tamimi, RM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA. EM nhrmt@channing.harvard.edu; lindquist_admin@wi.mit.edu; tince@med.miami.edu FU Breast Cancer Research Foundation (New York, NY); National Cancer Institute [R01-CA146445-01, CA089393]; Department of Defense [W81XWH-08-1-0282 BC-07456]; Public Health Service [CA087969]; Department of Health and Human Services; GlaxoSmithKline [WE234, EPI40307]; Susan G. Komen Breast Cancer Foundation; Howard Hughes Medical Institute; American Cancer Society New England Division [PF-09-253-01-DMC]; National Institutes of Health [K08NS064168]; Marble Foundation; V Foundation for Cancer Research FX We thank the participants and staff of the NHS cohort for their valuable contributions. We thank the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. We thank Terri Woo for expert assistance with IHC. We acknowledge grants from the Breast Cancer Research Foundation (New York, NY), National Cancer Institute Grant R01-CA146445-01, and Department of Defense Congressionally Directed Medical Research Program Breast Cancer Research Program Grant W81XWH-08-1-0282 BC-07456 (to T.A.I.); Public Health Service Grant CA087969 (to S.E.H.); National Cancer Institute Specialized Program of Research Excellence (SPORE) in Breast Cancer Grant CA089393 (to Dirk Iglehart, Dana-Farber Cancer Institute); funds from the Department of Health and Human Services and GlaxoSmithKline Grant WE234, EPI40307 (to R.M.T.); grants from the Susan G. Komen Breast Cancer Foundation (to L.W. and N.U.L.); funding from the Howard Hughes Medical Institute (to S.L.); American Cancer Society New England Division-SpinOdyssey Postdoctoral Fellowship PF-09-253-01-DMC (to M.L.M.); and National Institutes of Health Grant K08NS064168 and funds from the Marble Foundation and the V Foundation for Cancer Research (to S.S.). NR 42 TC 94 Z9 96 U1 1 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 2011 VL 108 IS 45 BP 18378 EP 18383 DI 10.1073/pnas.1115031108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 843UT UT WOS:000296700000047 PM 22042860 ER PT J AU Rustagi, T Mashimo, H AF Rustagi, Tarun Mashimo, Hiroshi TI Endoscopic management of chronic radiation proctitis SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Review DE Chronic; Radiation proctitis; Endoscopic; Argon plasma coagulation; Radiofrequency; Cryoablation ID ARGON PLASMA COAGULATION; ND-YAG LASER; TERM-FOLLOW-UP; RADIOFREQUENCY ABLATION; DOUBLE-BLIND; BIPOLAR ELECTROCOAGULATION; INDUCED PROCTOSIGMOIDITIS; THERAPY; PROCTOPATHY; INJURY AB Chronic radiation proctopathy occurs in 5%-20% of patients following pelvic radiotherapy. Although many cases resolve spontaneously, some lead to chronic symptoms including diarrhea, tenesmus, urgency and persistent rectal bleeding with iron deficiency anemia requiring blood transfusions. Treatments for chronic radiation proctitis remain unsatisfactory and the basis of evidence for various therapies is generally insufficient. There are very few controlled or prospective trials, and comparisons between therapies are limited because of different evaluation methods. Medical treatments, including formalin, topical sucralfate, 5-amino salicylic acid enemas, and short chain fatty acids have been used with limited success. Surgical management is associated with high morbidity and mortality. Endoscopic therapy using modalities such as the heater probe, neodymium: yttrium-aluminium-garnet laser, potassium titanyl phosphate laser and bipolar electrocoagulation has been reported to be of some benefit, but with frequent complications. Argon plasma coagulation is touted to be the preferred endoscopic therapy due to its efficacy and safety profile. Newer methods of endoscopic ablation such as radiofrequency ablation and cryotherapy have been recently described which may afford broader areas of treatment per application, with lower rate of complications. This review will focus on endoscopic ablation therapies, including such newer modalities, for chronic radiation proctitis. (C) 2011 Baishideng. All rights reserved. C1 [Mashimo, Hiroshi] Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst,Gastroenterol Sect 111, Boston, MA 02130 USA. [Rustagi, Tarun] Univ Connecticut, Dept Internal Med, Farmington, CT 06030 USA. RP Mashimo, H (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst,Gastroenterol Sect 111, 150 S Huntington Ave, Boston, MA 02130 USA. EM hmashimo@hms.harvard.edu NR 85 TC 25 Z9 27 U1 0 U2 0 PU BAISHIDENG PUBL GRP CO LTD PI BEIJING PA RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD NOV 7 PY 2011 VL 17 IS 41 BP 4554 EP 4562 DI 10.3748/wjg.v17.i41.4554 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 861ER UT WOS:000298002500002 PM 22147960 ER PT J AU Rugge, M Fassan, M Pizzi, M Farinati, F Sturniolo, GC Plebani, M Graham, DY AF Rugge, Massimo Fassan, Matteo Pizzi, Marco Farinati, Fabio Sturniolo, Giacomo Carlo Plebani, Mario Graham, David Y. TI Operative link for gastritis assessment vs operative link on intestinal metaplasia assessment SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Gastritis; Staging; Atrophic gastritis; Intestinal metaplasia; Operative link for gastritis assessment; Operative link on intestinal metaplasia assessment ID LYMPH-NODE DISSECTION; ASSISTED DISTAL GASTRECTOMY; OPEN SUBTOTAL GASTRECTOMY; BILLROTH-I GASTRECTOMY; QUALITY-OF-LIFE; CANCER; TRIAL AB AIM: To compare the reliability of gastritis staging systems in ranking gastritis-associated cancer risk in a large series of consecutive patients. METHODS: Gastric mucosal atrophy is the precancerous condition in which intestinal-type gastric cancer (GC) most frequently develops. The operative link for gastritis assessment (OLGA) staging system ranks the GC risk according to both the topography and the severity of gastric atrophy (as assessed histologically on the basis of the Sydney protocol for gastric mucosal biopsy). Both cross-sectional and long-term follow-up trials have consistently associated OLGA stages III-IV with a higher risk of GC. A recently-proposed modification of the OLGA staging system (OLGIM) basically incorporates the OLGA frame, but replaces the atrophy score with an assessment of intestinal metaplasia (IM) alone. A series of 4552 consecutive biopsy sets (2007-2009) was retrieved and reassessed according to both the OLGA and the OLGIM staging systems. A set of at least 5 biopsy samples was available for all the cases considered. RESULTS: In 4460 of 4552 cases (98.0%), both the high-risk stages (III + IV) and the low-risk stages (0 + I + II) were assessed applying the OLGA and OLGIM criteria. Among the 243 OLGA high-risk stages, 14 (5.8%) were down-staged to a low risk using OLGIM. The 67 (1.5%) incidentally-found neoplastic lesions (intraepithelial or invasive) were consistently associated with high-risk stages, as assessed by both OLGA and OLGIM (P < 0.001 for both). Two of 34 intestinal-type GCs coexisting with a high-risk OLGA stage (stage III) were associated with a low-risk OLGIM stage (stage II). CONCLUSION: Gastritis staging systems (both OLGA and OLGIM) convey prognostically important information on the gastritis-associated cancer risk. Because of its clinical impact, the stage of gastritis should be included as a conclusive message in the gastritis histology report. Since it focuses on IM alone, OLGIM staging is less sensitive than OLGA staging in the identification of patients at high risk of gastric cancer. (C) 2011 Baishideng. All rights reserved. C1 [Rugge, Massimo] Univ Padua, Surg Pathol & Cytopathol Unit, Dept Med Diagnost Sci & Special Therapies, Ist Oncol Veneto IOV IRCCS, I-35100 Padua, Italy. [Farinati, Fabio; Sturniolo, Giacomo Carlo] Univ Padua, Dept Gastroenterol & Surg Sci, Gastroenterol Unit, I-35100 Padua, Italy. [Plebani, Mario] Univ Padua, Dept Diagnost Med Sci & Special Therapies, Clin Chem Unit, I-35100 Padua, Italy. [Graham, David Y.] Vet Adm Hosp, Baylor Coll Med, Div Digest Dis, Houston, TX 77030 USA. RP Rugge, M (reprint author), Univ Padua, Surg Pathol & Cytopathol Unit, Dept Med Diagnost Sci & Special Therapies, Ist Oncol Veneto IOV IRCCS, Via Aristide Gabelli 61, I-35100 Padua, Italy. EM massimo.rugge@unipd.it RI Fassan, Matteo/F-5152-2012; Rugge, Massimo/K-7525-2016 OI Fassan, Matteo/0000-0001-6515-5482; FU AIRC from the Veneto Regional Authorities; "Guido Berlucchi" Foundation; "Morgagni" Association for Oncological Research (Padova; PD) FX Supported by An AIRC grant from the Veneto Regional Authorities, 2009; the "Guido Berlucchi" Foundation; and the "Morgagni" Association for Oncological Research (Padova; PD) NR 18 TC 26 Z9 27 U1 0 U2 2 PU BAISHIDENG PUBL GRP CO LTD PI BEIJING PA RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD NOV 7 PY 2011 VL 17 IS 41 BP 4596 EP 4606 DI 10.3748/wjg.v17.i41.4596 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 861ER UT WOS:000298002500007 PM 22147965 ER PT J AU McQuaid, D Bortfeld, T AF McQuaid, D. Bortfeld, T. TI 4D planning over the full course of fractionation: assessment of the benefit of tumor trailing SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID TRACKING SYSTEM; MOTION; RADIOTHERAPY; ERRORS AB Tumor trailing techniques have been proposed as a method of reducing the problem of intrafraction motion in radiotherapy. However the dosimetric assessment of trailing strategies is complicated by the requirement to study dose deposition over a full fraction delivery. Common 4D planning strategies allowing assessment of dosimetric motion effects study a single cycle acquired with 4DCT. In this paper, a methodology to assess dose deposited over an entire treatment course is advanced and used to assess the potential benefit of tumor trailing strategies for lung cancer patients. Two digital phantoms mimicking patient anatomy were each programmed to follow the tumor respiratory trajectory observed from 33 lung cancer patients. The two phantoms were designed to represent the cases of a small (volume = 13.6 cm(3)) and large (volume = 181.7 cm(3)) lung lesion. Motion margins required to obtain CTV coverage by 95% of the prescription dose to 90% of the available cases were computed for a standard treatment strategy and a trailing treatment strategy. The trailing strategy facilitated a margin reduction of over 30% relative to the conventional delivery. When the dose was computed across the entire delivery for the 33 cases, the trailing strategy was found to significantly reduce the underdosage to the outlier cases and the reduced trailing margin facilitated a 15% (small lesion) and 4% (large lesion) reduction for the mean lung dose and 7% (small lesion) and 10% (large lesion) for the mean esophagus dose. Finally, for comparison an ideal continuous tracking strategy was assessed and found to further reduce the mean lung and esophagus dose. However, this improvement comes at the price of increased delivery complexity and increased reliance on tumor localization accuracy. C1 [McQuaid, D.; Bortfeld, T.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP McQuaid, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM dualta.mcquaid@icr.ac.uk FU National Cancer Institute [5R01CA118200-05] FX This work has been supported by the National Cancer Institute under grant number 5R01CA118200-05. The authors would like to thank Greg Sharp, Alex Trofimov, Jan Unkelbach and David Craft for their useful discussions and Hiroki Shirato and Greg Sharp for their work on the patient data used in this study. NR 16 TC 3 Z9 3 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD NOV 7 PY 2011 VL 56 IS 21 BP 6935 EP 6949 DI 10.1088/0031-9155/56/21/011 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 842NH UT WOS:000296605700012 PM 22008696 ER PT J AU Sikorski, TW Ficarro, SB Holik, J Kim, T Rando, OJ Marto, JA Buratowski, S AF Sikorski, Timothy W. Ficarro, Scott B. Holik, John Kim, TaeSoo Rando, Oliver J. Marto, Jarrod A. Buratowski, Stephen TI Sub1 and RPA Associate with RNA Polymerase II at Different Stages of Transcription SO MOLECULAR CELL LA English DT Article ID REPLICATION PROTEIN-A; PC4 COACTIVATOR FUNCTION; MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; MULTIPLE FUNCTIONS; PREINITIATION COMPLEX; GENE-TRANSCRIPTION; BINDING PROTEIN; TERMINAL DOMAIN; DYNAMIC-MODEL AB Single-stranded DNA-binding proteins play many roles in nucleic acid metabolism, but their importance during transcription remains unclear. Quantitative proteomic analysis of RNA polymerase II (RNApII) preinitiation complexes (PICs) identified Sub1 and the replication protein A complex (RPA), both of which bind single-stranded DNA (ssDNA). Sub1, homolog of mammalian coactivator PC4, exhibits strong genetic interactions with factors necessary for promoter melting. Sub1 localizes near the transcription bubble in vitro and binds to promoters in vivo dependent upon PIC assembly. In contrast, RPA localizes to transcribed regions of active genes, strongly correlated with transcribing RNApII but independently of replication. RFA1 interacts genetically with transcription elongation factor genes. Interestingly, RPA levels increase at active promoters in cells carrying a Sub1 deletion or ssDNA-binding mutant, suggesting competition for a common binding site. We propose that Sub1 and RPA interact with the nontemplate strand of RNApII complexes during initiation and elongation, respectively. C1 [Sikorski, Timothy W.; Ficarro, Scott B.; Kim, TaeSoo; Marto, Jarrod A.; Buratowski, Stephen] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Sikorski, Timothy W.; Ficarro, Scott B.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ficarro, Scott B.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Holik, John; Rando, Oliver J.] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA USA. RP Marto, JA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM jarrod_marto@dfci.harvard.edu; steveb@hms.harvard.edu FU NIH [GM46498]; Burroughs Wellcome Fund Career Award in the Biomedical Sciences; NIGMS [GM079205]; DFCI/Blaise Proteomics Center; NDSEG FX We thank Olga Calvo, Steve Hahn, Richard Kolodner, Michael Hampsey, and Claire Moore for strains and plasmids; Steven Brill for the Rfa1 antibody; Manor Askenazi and Jignesh Parikh for help with mass spectrometry and microarray data analysis; and Minkyu Kim, Sebastian Marquardt, and Nihal Terzi for technical assistance. We also thank Steve Hahn, Michael Meisterernst, Olga Ca Ivo, Alicia Martinez, Doug Koshland, and members of the Buratowski and Marto labs for helpful discussions. This work was supported by NIH grant GM46498 to S.B., a Burroughs Wellcome Fund Career Award in the Biomedical Sciences and NIGMS grant GM079205 to O.J.R., DFCI/Blaise Proteomics Center support to J.M., and a NDSEG predoctoral fellowship to T.S. NR 75 TC 35 Z9 36 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD NOV 4 PY 2011 VL 44 IS 3 BP 397 EP 409 DI 10.1016/j.molcel.2011.09.013 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 844OE UT WOS:000296756100008 PM 22055186 ER PT J AU Junqueira, JC Fuchs, BB Muhammed, M Coleman, JJ Suleiman, JMAH Vilela, SFG Costa, ACBP Rasteiro, VMC Jorge, AOC Mylonakis, E AF Junqueira, Juliana C. Fuchs, Beth B. Muhammed, Maged Coleman, Jeffrey J. Suleiman, Jamal M. A. H. Vilela, Simone F. G. Costa, Anna C. B. P. Rasteiro, Vanessa M. C. Jorge, Antonio O. C. Mylonakis, Eleftherios TI Oral Candida albicans isolates from HIV-positive individuals have similar in vitro biofilm-forming ability and pathogenicity as invasive Candida isolates SO BMC MICROBIOLOGY LA English DT Article ID GALLERIA-MELLONELLA LARVAE; FUNGAL PATHOGENESIS; MODEL HOST; INFECTION; VIRULENCE; DUBLINIENSIS; COLONIZATION; SUSCEPTIBILITY; EXPRESSION; RESISTANCE AB Background: Candida can cause mucocutaneous and/or systemic infections in hospitalized and immunosuppressed patients. Most individuals are colonized by Candida spp. as part of the oral flora and the intestinal tract. We compared oral and systemic isolates for the capacity to form biofilm in an in vitro biofilm model and pathogenicity in the Galleria mellonella infection model. The oral Candida strains were isolated from the HIV patients and included species of C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, C. norvegensis, and C. dubliniensis. The systemic strains were isolated from patients with invasive candidiasis and included species of C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. lusitaniae, and C. kefyr. For each of the acquired strains, biofilm formation was evaluated on standardized samples of silicone pads and acrylic resin. We assessed the pathogenicity of the strains by infecting G. mellonella animals with Candida strains and observing survival. Results: The biofilm formation and pathogenicity in Galleria was similar between oral and systemic isolates. The quantity of biofilm formed and the virulence in G. mellonella were different for each of the species studied. On silicone pads, C. albicans and C. dubliniensis produced more biofilm (1.12 to 6.61 mg) than the other species (0.25 to 3.66 mg). However, all Candida species produced a similar biofilm on acrylic resin, material used in dental prostheses. C. albicans, C. dubliniensis, C. tropicalis, and C. parapsilosis were the most virulent species in G. mellonella with 100% of mortality, followed by C. lusitaniae (87%), C. novergensis (37%), C. krusei (25%), C. glabrata (20%), and C. kefyr (12%). Conclusions: We found that on silicone pads as well as in the Galleria model, biofilm formation and virulence depends on the Candida species. Importantly, for C. albicans the pathogenicity of oral Candida isolates was similar to systemic Candida isolates, suggesting that Candida isolates have similar biofilm-forming ability and virulence regardless of the infection site from which it was isolated. C1 [Junqueira, Juliana C.; Vilela, Simone F. G.; Costa, Anna C. B. P.; Rasteiro, Vanessa M. C.; Jorge, Antonio O. C.] Univ Estadual Paulista UNESP, Dept Biosci & Oral Diag, BR-12245000 Sao Jose Dos Campos, SP, Brazil. [Fuchs, Beth B.; Muhammed, Maged; Coleman, Jeffrey J.; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Suleiman, Jamal M. A. H.] Emilio Ribas Inst Infectol, BR-01246900 Sao Paulo, Brazil. RP Junqueira, JC (reprint author), Univ Estadual Paulista UNESP, Dept Biosci & Oral Diag, 777 Av Eng Francisco Jose Longo, BR-12245000 Sao Jose Dos Campos, SP, Brazil. EM juliana@fosjc.unesp.br RI Junqueira, Juliana/F-7785-2012; vilela, simone/B-8728-2014; Coleman, Jeffrey/E-2981-2015; OI Coleman, Jeffrey/0000-0001-8579-1996 FU Sao Paulo Council of Research - FAPESP, Brazil [09/52283-0]; Univ Estadual Paulista - PROPG/UNESP FX This study was supported by the Sao Paulo Council of Research - FAPESP, Brazil (Grant no 09/52283-0) and Univ Estadual Paulista - PROPG/UNESP. NR 43 TC 24 Z9 25 U1 0 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD NOV 4 PY 2011 VL 11 AR 247 DI 10.1186/1471-2180-11-247 PG 9 WC Microbiology SC Microbiology GA 848MQ UT WOS:000297056100001 PM 22053894 ER PT J AU Rapley, J Oshiro, N Ortiz-Vega, S Avruch, J AF Rapley, Joseph Oshiro, Noriko Ortiz-Vega, Sara Avruch, Joseph TI The Mechanism of Insulin-stimulated 4E-BP Protein Binding to Mammalian Target of Rapamycin (mTOR) Complex 1 and Its Contribution to mTOR Complex 1 Signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RICH AKT SUBSTRATE; AMINO-ACID SUFFICIENCY; P70 S6 KINASE; 40 KDA PRAS40; CELL-GROWTH; DISTINCT ROLES; RAG GTPASES; TOS MOTIF; IN-VITRO; RAPTOR AB Insulin activation of mTOR complex 1 is accompanied by enhanced binding of substrates. We examined the mechanism and contribution of this enhancement to insulin activation of mTORC1 signaling in 293E and HeLa cells. In 293E, insulin increased the amount of mTORC1 retrieved by the transiently expressed nonphosphorylatable 4E-BP[5A] to an extent that varied inversely with the amount of PRAS40 bound to mTORC1. RNAi depletion of PRAS40 enhanced 4E-BP[5A] binding to similar to 70% the extent of maximal insulin, and PRAS40 RNAi and insulin together did not increase 4E-BP[5A] binding beyond insulin alone, suggesting that removal of PRAS40 from mTORC1 is the predominant mechanism of an insulin-induced increase in substrate access. As regards the role of increased substrate access in mTORC1 signaling, RNAi depletion of PRAS40, although increasing 4E-BP[5A] binding, did not stimulate phosphorylation of endogenous mTORC1 substrates S6K1(Thr(389)) or 4E-BP (Thr(37)/Thr(46)), the latter already similar to 70% of maximal in amino acid replete, serum-deprived 293E cells. In HeLa cells, insulin and PRAS40 RNAi also both enhanced the binding of 4E-BP[5A] to raptor but only insulin stimulated S6K1 and 4E-BP phosphorylation. Furthermore, Rheb overexpression in 293E activated mTORC1 signaling completely without causing PRAS40 release. In the presence of Rheb and insulin, PRAS40 release is abolished by Akt inhibition without diminishing mTORC1 signaling. In conclusion, dissociation of PRAS40 from mTORC1 and enhanced mTORC1 substrate binding results from Akt and mTORC1 activation and makes little or no contribution to mTORC1 signaling, which rather is determined by Rheb activation of mTOR catalytic activity, through mechanisms that remain to be fully elucidated. C1 [Avruch, Joseph] Massachusetts Gen Hosp, Diabet Res Lab, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Diabet Res Lab, Dept Mol Biol, Simches Res Bldg 6408,185 Cambridge St, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu FU National Institutes of Health [DK17776, CA73818] FX This work was supported, in whole or in part, by National Institutes of Health Grants DK17776 and CA73818. NR 42 TC 19 Z9 20 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 4 PY 2011 VL 286 IS 44 BP 38043 EP 38053 DI 10.1074/jbc.M111.245449 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 842JD UT WOS:000296594200016 PM 21914810 ER PT J AU Liu, Z Turan, S Wehbi, VL Vilardaga, JP Bastepe, M AF Liu, Zun Turan, Serap Wehbi, Vanessa L. Vilardaga, Jean-Pierre Bastepe, Murat TI Extra-long G alpha s Variant XL alpha s Protein Escapes Activation-induced Subcellular Redistribution and Is Able to Provide Sustained Signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STIMULATORY G-PROTEIN; MCCUNE-ALBRIGHT-SYNDROME; GNAS1 T393C POLYMORPHISM; PARATHYROID-HORMONE RECEPTOR; COUPLED RECEPTORS; ADENYLYL-CYCLASE; CELL CARCINOMA; FREE SURVIVAL; GENE VARIANT; SUBUNIT AB Murine models indicate that G alpha s and its extra-long variant XL alpha s, both of which are derived from GNAS, markedly differ regarding their cellular actions, but these differences are unknown. Here we investigated activation-induced trafficking of G alpha s and XL alpha s, using immunofluorescence microscopy, cell fractionation, and total internal reflection fluorescence microscopy. In transfected cells, XL alpha s remained localized to the plasma membrane, whereas G alpha s redistributed to the cytosol after activation by GTPase-inhibiting mutations, cholera toxin treatment, or G protein-coupled receptor agonists (isoproterenol or parathyroid hormone (PTH)(1-34)). Cholera toxin treatment or agonist (isoproterenol or pituitary adenylate cyclase activating peptide-27) stimulation of PC12 cells expressing G alpha s and XL alpha s endogenously led to an increased abundance of G alpha s, but not XL alpha s, in the soluble fraction. Mutational analyses revealed two conserved cysteines and the highly charged domain as being critically involved in the plasma membrane anchoring of XL alpha s. The cAMP response induced by M-PTH(1-14), a parathyroid hormone analog, terminated quickly in HEK293 cells stably expressing the type 1 PTH/PTH-related peptide receptor, whereas the response remained maximal for at least 6 min in cells that co-expressed the PTH receptor and XL alpha s. Although isoproterenol-induced cAMP response was not prolonged by XL alpha s expression, a GTPase-deficient XL alpha s mutant found in certain tumors and patients with fibrous dysplasia of bone and McCune-Albright syndrome generated more basal cAMP accumulation in HEK293 cells and caused more severe impairment of osteoblastic differentiation of MC3T3-E1 cells than the cognate G alpha s mutant (gsp oncogene). Thus, activated XL alpha s and G alpha s traffic differently, and this may form the basis for the differences in their cellular actions. C1 [Liu, Zun; Turan, Serap; Vilardaga, Jean-Pierre; Bastepe, Murat] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Liu, Zun; Turan, Serap; Vilardaga, Jean-Pierre; Bastepe, Murat] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Turan, Serap] Marmara Univ, Sch Med Hosp, TR-34662 Istanbul, Turkey. [Wehbi, Vanessa L.; Vilardaga, Jean-Pierre] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Lab Protein Coupled Receptor Biol G, Pittsburgh, PA 15213 USA. RP Bastepe, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, 50 Blossom St Thier 10, Boston, MA 02114 USA. EM bastepe@helix.mgh.harvard.edu FU National Institutes of Health from NIDDK [R01DK073911, R01DK087688]; March of Dimes Foundation [6-FY10-336]; European Society for Paediatric Endocrinology through Lilly, LLC. FX This work was supported, in whole or in part, by National Institutes of Health Grants R01DK073911 (to M. B.) and R01DK087688 (to J.-P. V.) from NIDDK. This work was also supported in part by March of Dimes Foundation Research Grant 6-FY10-336 (to M. B.).; Supported by a grant of the Sabbatical Leave Programme from the European Society for Paediatric Endocrinology through an educational grant from Lilly, LLC. NR 69 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 4 PY 2011 VL 286 IS 44 BP 38558 EP 38569 DI 10.1074/jbc.M111.240150 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 842JD UT WOS:000296594200069 PM 21890629 ER PT J AU Lee, E Kamlet, AS Powers, DC Neumann, CN Boursalian, GB Furuya, T Choi, DC Hooker, JM Ritter, T AF Lee, Eunsung Kamlet, Adam S. Powers, David C. Neumann, Constanze N. Boursalian, Gregory B. Furuya, Takeru Choi, Daniel C. Hooker, Jacob M. Ritter, Tobias TI A Fluoride-Derived Electrophilic Late-Stage Fluorination Reagent for PET Imaging SO SCIENCE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; REDUCTIVE ELIMINATION; RADIOSYNTHESIS; F-18 AB The unnatural isotope fluorine-18 (F-18) is used as a positron emitter in molecular imaging. Currently, many potentially useful F-18-labeled probe molecules are inaccessible for imaging because no fluorination chemistry is available to make them. The 110-minute half-life of F-18 requires rapid syntheses for which [F-18]fluoride is the preferred source of fluorine because of its practical access and suitable isotope enrichment. However, conventional [F-18]fluoride chemistry has been limited to nucleophilic fluorination reactions. We report the development of a palladium-based electrophilic fluorination reagent derived from fluoride and its application to the synthesis of aromatic F-18-labeled molecules via late-stage fluorination. Late-stage fluorination enables the synthesis of conventionally unavailable positron emission tomography (PET) tracers for anticipated applications in pharmaceutical development as well as preclinical and clinical PET imaging. C1 [Hooker, Jacob M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Lee, Eunsung; Kamlet, Adam S.; Powers, David C.; Neumann, Constanze N.; Boursalian, Gregory B.; Furuya, Takeru; Choi, Daniel C.; Ritter, Tobias] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Hooker, Jacob M.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Hooker, Jacob M.; Ritter, Tobias] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. RP Hooker, JM (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM hooker@nmr.mgh.harvard.edu; ritter@chemistry.harvard.edu RI Furuya, Takeru/A-6622-2012; Ritter, Tobias/A-6244-2013; Lee, Eunsung/F-5308-2013; Powers, David/J-8203-2015; Boursalian, Gregory/M-7729-2016; OI Ritter, Tobias/0000-0002-5478-0036; Powers, David/0000-0003-3717-2001; Boursalian, Gregory/0000-0002-6644-0987; Hooker, Jacob/0000-0002-9394-7708 FU National Institute of General Medical Sciences [GM088237]; National Institute of Biomedical Imaging and Bioengineering [EB013042]; National Center for Research Resources [1S10RR017208-01A1]; National Institute on Drug Abuse [5P30DA028800-02]; Richard and Susan Smith Family Foundation; Massachusetts Life Science Center; Harvard Catalyst; NSF [DGE0644491]; Harvard Accelerator Fund; Sloan Research Fellowship; Eli Lilly and Co.; AstraZeneca; Camille Dreyfus; Amgen FX Supported by National Institute of General Medical Sciences grant GM088237, National Institute of Biomedical Imaging and Bioengineering grant EB013042, National Center for Research Resources grant 1S10RR017208-01A1, National Institute on Drug Abuse grant 5P30DA028800-02, the Richard and Susan Smith Family Foundation, the Massachusetts Life Science Center, the Harvard Catalyst, NSF Graduate Research Fellowship Program grant DGE0644491, and the Harvard Accelerator Fund. T.R. was also supported by a Sloan Research Fellowship, grants from Eli Lilly and Co. and AstraZeneca, a Camille Dreyfus Teacher-Scholar Award, and an Amgen Young Investigators Award. We thank S.-L. Zheng for x-ray crystallographic analysis. DFT computation was performed using the computer facilities at the Odyssey cluster at Harvard University. Metrical parameters for the crystal structures of compounds 1, 2, 3, 8, and S10 are available free of charge from the Cambridge Crystallographic Data Centre under reference nos. CCDC 829427, 829428, 840744, 829429, and 839058, respectively. A patent application has been filed through Harvard on methods and reagents presented in this manuscript. NR 29 TC 187 Z9 187 U1 10 U2 133 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 4 PY 2011 VL 334 IS 6056 BP 639 EP 642 DI 10.1126/science.1212625 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 841EG UT WOS:000296494700046 PM 22053044 ER PT J AU Jacobson, CA Ritz, J AF Jacobson, Caron A. Ritz, Jerome TI Time to put the CAR-T before the horse SO BLOOD LA English DT Editorial Material ID DOMAINS C1 [Jacobson, Caron A.; Ritz, Jerome] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jacobson, CA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [P01 CA142106, T32 CA009172] NR 6 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 3 PY 2011 VL 118 IS 18 BP 4761 EP 4762 PG 2 WC Hematology SC Hematology GA 843YS UT WOS:000296714500001 PM 22053170 ER PT J AU Kawano, Y Kim, HT Matsuoka, K Bascug, G McDonough, S Ho, VT Cutler, C Koreth, J Alyea, EP Antin, JH Soiffer, RJ Ritz, J AF Kawano, Yutaka Kim, Haesook T. Matsuoka, Ken-ichi Bascug, Gregory McDonough, Sean Ho, Vincent T. Cutler, Corey Koreth, John Alyea, Edwin P. Antin, Joseph H. Soiffer, Robert J. Ritz, Jerome TI Low telomerase activity in CD4(+) regulatory T cells in patients with severe chronic GVHD after hematopoietic stem cell transplantation SO BLOOD LA English DT Article ID VERSUS-HOST-DISEASE; CHROMOSOME INSTABILITY; INDUCED APOPTOSIS; GRAFT; HTERT; ACTIVATION; CANCER; LENGTH; RISK; DYSFUNCTION AB CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) play an important role in the control of chronic graft-versus-host disease (cGVHD). In this study, we examined telomere length and telomerase activity of Treg and conventional CD4(+) T cells (Tcon) in 61 patients who survived more than 2 years after allogeneic hematopoietic stem cell transplantation. Cell proliferation and expression of Bcl-2 were also measured in each subset. Treg telomere length was shorter and Treg telomerase activity was increased compared with Tcon (P < .0001). After transplantation, Treg were also more highly proliferative than Tcon (P < .0001). Treg number, telomerase activity, and expression of Bcl-2 were each inversely associated with severity of cGVHD. These data indicate that activation of telomerase is not sufficient to prevent telomere shortening in highly proliferative Treg. However, telomerase activation is associated with increased Bcl-2 expression and higher Treg numbers in patients with no or mild cGVHD. In contrast, patients with moderate or severe cGVHD have fewer Treg with lower levels of telomerase activity and Bcl-2 expression. These results suggest that failure to activate Treg telomerase may restrict proliferative capacity and increase apoptotic susceptibility, resulting in the loss of peripheral tolerance and the development of cGVHD. (Blood. 2011; 118(18):5021-5030) C1 [Kawano, Yutaka; Matsuoka, Ken-ichi; Bascug, Gregory; McDonough, Sean; Ho, Vincent T.; Cutler, Corey; Koreth, John; Alyea, Edwin P.; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Kawano, Yutaka; Matsuoka, Ken-ichi; Bascug, Gregory; McDonough, Sean; Ho, Vincent T.; Cutler, Corey; Koreth, John; Alyea, Edwin P.; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Kawano, Yutaka; Matsuoka, Ken-ichi; Ho, Vincent T.; Cutler, Corey; Koreth, John; Alyea, Edwin P.; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA USA. [Kim, Haesook T.; Ritz, Jerome] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA USA. [Kim, Haesook T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Ritz, Jerome] Harvard Stem Cell Inst, Boston, MA USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 450 Brookline Ave, Boston, MA 02115 USA. EM jerome_ritz@dfci.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU National Institutes of Health [AI29530, CA142106]; Jock and Bunny Adams Education and Research Endowment; Ted and Eileen Pasquarello Research Fund FX This work was supported by the National Institutes of Health (grants AI29530 and CA142106), the Jock and Bunny Adams Education and Research Endowment, and the Ted and Eileen Pasquarello Research Fund. NR 43 TC 18 Z9 19 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 3 PY 2011 VL 118 IS 18 BP 5021 EP 5030 DI 10.1182/blood-2011-06-362137 PG 10 WC Hematology SC Hematology GA 843YS UT WOS:000296714500033 PM 21900196 ER PT J AU Lee, AI Koo, S Vaidya, A Katz, JT Loscalzo, J AF Lee, Alfred Ian Koo, Sophia Vaidya, Anand Katz, Joel T. Loscalzo, Joseph TI A Bird's-Eye View of Fever SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HISTOPLASMA-CAPSULATUM; ENDOPHTHALMITIS; MYCOSES; UPDATE; TISSUE C1 [Lee, Alfred Ian; Koo, Sophia; Vaidya, Anand; Katz, Joel T.; Loscalzo, Joseph] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Lee, Alfred Ian] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Katz, JT (reprint author), 75 Francis St, Boston, MA 02115 USA. EM jkatz@partners.org OI Koo, Sophia/0000-0002-4973-7439 NR 14 TC 0 Z9 0 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 3 PY 2011 VL 365 IS 18 BP 1727 EP 1732 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 840FL UT WOS:000296424200013 PM 22047564 ER PT J AU Yoon, TJ Lee, H Shao, HL Hilderbrand, SA Weissleder, R AF Yoon, Tae-Jong Lee, Hakho Shao, Huilin Hilderbrand, Scott A. Weissleder, Ralph TI Multicore Assemblies Potentiate Magnetic Properties of Biomagnetic Nanoparticles SO ADVANCED MATERIALS LA English DT Article ID CORE-SHELL NANOPARTICLES; ULTRASENSITIVE DETECTION; DRUG-DELIVERY; RESONANCE; SPHERES; CELLS; MRI; SEPARATION; THERAPY; CANCER AB Highly potent magnetic nanomaterials are developed by encasing multiple magnetic cores inside a thin silica shell, in much the same way as the pomegranate fruit contains many seeds within a thin skin. This construct not only produces materials that are biocompatible but also ones that reach theoretically maximum transverse relaxivity. C1 [Yoon, Tae-Jong; Lee, Hakho; Shao, Huilin; Hilderbrand, Scott A.; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Yoon, Tae-Jong] CHA Univ, Dept Appl Biosci, Seoul 135081, South Korea. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Lee, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM hlee@mgh.harvard.edu; rweissleder@mgh.harvard.edu FU National Institute of Health [R01-EB0044626, R01-EB010011, P50CA86355]; CCNE [U54CA151884]; TPEN [HHSN268201000044C] FX T.J.Y. and H. L. contributed equally to this work. The authors thank: C. Ross (MIT) for his generous support in performing magnetic measurements; P. Waterman, J. Donahoe, G. Wojtkiewicz, J. Figueiredo, J. Chen, and M. Nahrendorf for assistance in MRI and FMT; N. Sergeyev for synthesizing CLIO; and Y. Fisher-Jeffes for reviewing the manuscript. This work was supported in part by National Institute of Health Grants R01-EB0044626, R01-EB010011, P50 grant P50CA86355, CCNE contract U54CA151884, and TPEN contract HHSN268201000044C. NR 35 TC 52 Z9 52 U1 5 U2 54 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0935-9648 J9 ADV MATER JI Adv. Mater. PD NOV 2 PY 2011 VL 23 IS 41 BP 4793 EP + DI 10.1002/adma.201102948 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 848HD UT WOS:000297041600007 PM 21953810 ER PT J AU Banks, AS Kim-Muller, JY Mastracci, TL Kofler, NM Qiang, L Haeusler, RA Jurczak, MJ Laznik, D Heinrich, G Samuel, VT Shulman, GI Papaioannou, VE Accili, D AF Banks, Alexander S. Kim-Muller, Ja Young Mastracci, Teresa L. Kofler, Natalie M. Qiang, Li Haeusler, Rebecca A. Jurczak, Michael J. Laznik, Dina Heinrich, Garrett Samuel, Varman T. Shulman, Gerald I. Papaioannou, Virginia E. Accili, Domenico TI Dissociation of the Glucose and Lipid Regulatory Functions of FoxO1 by Targeted Knockin of Acetylation-Defective Alleles in Mice SO CELL METABOLISM LA English DT Article ID TRANSCRIPTION FACTOR FOXO1; HEPATIC INSULIN-RESISTANCE; ACTIVATED RECEPTOR-GAMMA; FORKHEAD PROTEIN FOXO1; CAENORHABDITIS-ELEGANS; DEPENDENT REGULATION; FOOD-INTAKE; GENE; DIFFERENTIATION; LIVER AB FoxO1 integrates multiple metabolic pathways. Nutrient levels modulate FoxO1 acetylation, but the functional consequences of this posttranslational modification are unclear. To answer this question, we generated mice bearing alleles that encode constitutively acetylated and acetylation-defective FoxO1 proteins. Homozygosity for an allele mimicking constitutive acetylation (Foxo1(KQ/KQ)) results in embryonic lethality due to cardiac and angiogenesis defects. In contrast, mice homozygous for a constitutively deacetylated Foxo1 allele (Foxo1(KR/KR)) display a unique metabolic phenotype of impaired insulin action on hepatic glucose metabolism but decreased plasma lipid levels and low respiratory quotient that are consistent with a state of preferential lipid usage. Moreover, Foxo1KR/KR mice show a dissociation between weight gain and insulin resistance in predisposing conditions (high fat diet, diabetes, and insulin receptor mutations), possibly due to decreased cytokine production in adipose tissue. Thus, acetylation inactivates FoxO1 during nutrient excess whereas deacetylation selectively potentiates FoxO1 activity, protecting against excessive catabolism during nutrient deprivation. C1 [Banks, Alexander S.; Kim-Muller, Ja Young; Kofler, Natalie M.; Qiang, Li; Haeusler, Rebecca A.; Heinrich, Garrett; Accili, Domenico] Columbia Univ, Dept Med, New York, NY 10032 USA. [Mastracci, Teresa L.; Papaioannou, Virginia E.] Columbia Univ, Dept Genet & Dev, Coll Phys & Surg, New York, NY 10032 USA. [Banks, Alexander S.; Laznik, Dina] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Laznik, Dina] Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. [Laznik, Dina] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Jurczak, Michael J.; Samuel, Varman T.; Shulman, Gerald I.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. [Jurczak, Michael J.; Samuel, Varman T.; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Jurczak, Michael J.; Samuel, Varman T.; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. RP Accili, D (reprint author), Columbia Univ, Dept Med, New York, NY 10032 USA. EM da230@columbia.edu RI Qiang, Li/C-9560-2012; Banks, Alexander/B-4832-2012; Mastracci, Teresa/C-4565-2013; OI Banks, Alexander/0000-0003-1787-6925; Jurczak, Michael/0000-0002-6335-6915 FU NIH [DK079496, DK057539, HL087123]; NIH, Columbia University Diabetes & Endocrinology Research Center [DK63608]; NIH, Yale Mouse Metabolic Phenotyping Center [DK059635] FX Supported by NIH grants DK079496 (to A.S.B.), DK057539 and HL087123 (to D.A.), DK63608 (Columbia University Diabetes & Endocrinology Research Center) and DK059635 (Yale Mouse Metabolic Phenotyping Center). We thank members of the Accili laboratory for helpful discussions of the data and critical reading of the manuscript, Dr. Thomas Ludwig for the gift of the DT-A plasmid, Dr. Lori Sussel for making her laboratory available for embryo analysis, and Dr. Bruce Spiegelman for guidance and support. NR 55 TC 32 Z9 33 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD NOV 2 PY 2011 VL 14 IS 5 BP 587 EP 597 DI 10.1016/j.cmet.2011.09.012 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 849RG UT WOS:000297142200005 PM 22055502 ER PT J AU Kramer, MA Eden, UT Lepage, KQ Kolaczyk, ED Bianchi, MT Cash, SS AF Kramer, Mark A. Eden, Uri T. Lepage, Kyle Q. Kolaczyk, Eric D. Bianchi, Matt T. Cash, Sydney S. TI Emergence of Persistent Networks in Long-Term Intracranial EEG Recordings SO JOURNAL OF NEUROSCIENCE LA English DT Article ID GRAPH-THEORETICAL ANALYSIS; COMPLEX BRAIN NETWORKS; STATE FUNCTIONAL CONNECTIVITY; POSITRON-EMISSION-TOMOGRAPHY; SMALL-WORLD; CEREBRAL-CORTEX; DEFAULT MODE; MEASURING SYNCHRONIZATION; GAMMA OSCILLATIONS; CORTICAL NETWORKS AB Over the past two decades, the increased ability to analyze network relationships among neural structures has provided novel insights into brain function. Most network approaches, however, focus on static representations of the brain's physical or statistical connectivity. Few studies have examined how brain functional networks evolve spontaneously over long epochs of continuous time. To address this, we examine functional connectivity networks deduced from continuous long-term electrocorticogram recordings. For a population of six human patients, we identify a persistent pattern of connections that form a frequency-band-dependent network template, and a set of core connections that appear frequently and together. These structures are robust, emerging from brief time intervals (similar to 100 s) regardless of cognitive state. These results suggest that a metastable, frequency-band-dependent scaffold of brain connectivity exists from which transient activity emerges and recedes. C1 [Kramer, Mark A.; Eden, Uri T.; Lepage, Kyle Q.; Kolaczyk, Eric D.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Bianchi, Matt T.; Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bianchi, Matt T.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Kramer, MA (reprint author), Boston Univ, Dept Math & Stat, 111 Cummington St, Boston, MA 02215 USA. EM mak@bu.edu RI Kramer, Mark/A-1291-2014 FU Burroughs Wellcome Fund; National Science Foundation [IIS-0643995]; Office of Naval Research [N00014-06-1-0096]; National Institutes of Health, National Institute of Neurological Disorders and Stroke [NS062092] FX M.A.K. holds a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. U.T.E. acknowledges support by the National Science Foundation under Grant IIS-0643995. E.D.K. acknowledges support by the Office of Naval Research Award N00014-06-1-0096. S.S.C. is supported by a grant from the National Institutes of Health, National Institute of Neurological Disorders and Stroke NS062092. We thank Emad Eskandar for electrode placement and surgical management. NR 83 TC 28 Z9 28 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 2 PY 2011 VL 31 IS 44 BP 15757 EP 15767 DI 10.1523/JNEUROSCI.2287-11.2011 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 844ES UT WOS:000296731100014 PM 22049419 ER PT J AU Chang, HJ Liang, MH AF Chang, Huan J. Liang, Matthew H. TI The Quiet Epidemic SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Liang, Matthew H.] Brigham & Womens Hosp, Rheumatol Sect, Boston VA Healthcare Syst, Rehabil Serv, Boston, MA 02115 USA. [Liang, Matthew H.] Brigham & Womens Hosp, Rheumatol Sect, Boston VA Healthcare Syst, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. EM tina.chang@jama-archives.org NR 1 TC 1 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 2 PY 2011 VL 306 IS 17 BP 1843 EP 1844 DI 10.1001/jama.2011.1587 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 839OD UT WOS:000296376200001 PM 22045757 ER PT J AU Sorror, ML Sandmaier, BM Storer, BE Franke, GN Laport, GG Chauncey, TR Agura, E Maziarz, RT Langston, A Hari, P Pulsipher, MA Bethge, W Sahebi, F Bruno, B Maris, MB Yeager, A Petersen, FB Vindelov, L McSweeney, PA Hubel, K Mielcarek, M Georges, GE Niederwieser, D Blume, KG Maloney, DG Storb, R AF Sorror, Mohamed L. Sandmaier, Brenda M. Storer, Barry E. Franke, Georg N. Laport, Ginna G. Chauncey, Thomas R. Agura, Edward Maziarz, Richard T. Langston, Amelia Hari, Parameswaran Pulsipher, Michael A. Bethge, Wolfgang Sahebi, Firoozeh Bruno, Benedetto Maris, Michael B. Yeager, Andrew Petersen, Finn Bo Vindelov, Lars McSweeney, Peter A. Huebel, Kai Mielcarek, Marco Georges, George E. Niederwieser, Dietger Blume, Karl G. Maloney, David G. Storb, Rainer TI Long-term Outcomes Among Older Patients Following Nonmyeloablative Conditioning and Allogeneic Hematopoietic Cell Transplantation for Advanced Hematologic Malignancies SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MYELOID-LEUKEMIA; VERSUS-HOST-DISEASE; MINIMAL RESIDUAL DISEASE; MARROW TRANSPLANTATION; MYELODYSPLASTIC SYNDROMES; COMORBIDITY INDEX; RISK-ASSESSMENT; FLOW-CYTOMETRY; AGE; METHOTREXATE AB Context A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions. Objective To describe outcomes of patients 60 years or older after receiving minimally toxic nonmyeloablative allogeneic HCT. Design, Setting, and Participants From 1998 to 2008, 372 patients aged 60 to 75 years were enrolled in prospective clinical HCT trials at 18 collaborating institutions using conditioning with low-dose total body irradiation alone or combined with fludarabine, 90 mg/m(2), before related (n=184) or unrelated (n=188) donor transplants. Postgrafting immunosuppression included mycophenolate mofetil and a calcineurin inhibitor. Main Outcome Measures Overall and progression-free survival were estimated by Kaplan-Meier method. Cumulative incidence estimates were calculated for acute and chronic graft-vs-host disease, toxicities, achievement of full donor chimerism, complete remission, relapse, and nonrelapse mortality. Hazard ratios (HRs) were estimated from Cox regression models. Results Overall, 5-year cumulative incidences of nonrelapse mortality and relapse were 27% (95% CI, 22%-32%) and 41% (95% CI, 36%-46%), respectively, leading to 5-year overall and progression-free survival of 35% (95% CI, 30%-40%) and 32% (95% CI, 27%-37%), respectively. These outcomes were not statistically significantly different when stratified by age groups. Furthermore, increasing age was not associated with increases in acute or chronic graft-vs-host disease or organ toxicities. In multivariate models, HCT-specific comorbidity index scores of 1 to 2 (HR, 1.58 [95% CI, 1.08-2.31]) and 3 or greater (HR, 1.97 [95% CI, 1.38-2.80]) were associated with worse survival compared with an HCT-specific comorbidity index score of 0 (P=.003 overall). Similarly, standard relapse risk (HR, 1.67 [95% CI, 1.10-2.54]) and high relapse risk (HR, 2.22 [95% CI, 1.43-3.43]) were associated with worse survival compared with low relapse risk (P<.001 overall). Conclusion Among patients aged 60 to 75 years treated with nonmyeloablative allogeneic HCT, 5-year overall and progression-free survivals were 35% and 32%, respectively. JAMA. 2011; 306(17): 1874-1883 C1 [Sorror, Mohamed L.; Sandmaier, Brenda M.; Chauncey, Thomas R.; Mielcarek, Marco; Georges, George E.; Maloney, David G.; Storb, Rainer] Fred Hutchinson Canc Res Ctr, Div Clin Res, Transplantat Biol Program, Seattle, WA 98109 USA. [Storer, Barry E.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Clin Stat Program, Seattle, WA 98109 USA. [Sorror, Mohamed L.; Sandmaier, Brenda M.; Chauncey, Thomas R.; Mielcarek, Marco; Georges, George E.; Maloney, David G.; Storb, Rainer] Univ Washington, Sch Med, Dept Med, Div Med Oncol, Seattle, WA 98195 USA. [Storer, Barry E.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Chauncey, Thomas R.] VA Puget Sound Hlth Care Syst, Marrow Transplant Unit, Seattle, WA USA. [Franke, Georg N.; Niederwieser, Dietger] Univ Leipzig, Dept Med, Div Hematol Oncol & Hemostaseol, Leipzig, Germany. [Laport, Ginna G.; Blume, Karl G.] Stanford Sch Med, Div Blood & Marrow Transplantat, Dept Med, Stanford, CA USA. [Agura, Edward] Baylor Univ, Hematopoiet Stem Cell Program, Sch Med, Dallas, TX USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Sch Med, Hematopoiet Stem Cell Transplant Program, Portland, OR 97201 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Sch Med, Ctr Hematol Malignancies, Knight Canc Inst, Portland, OR 97201 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Sch Med, Div Hematol & Med Oncol, Portland, OR 97201 USA. [Langston, Amelia] Emory Univ, Sch Med, Div Hematol Oncol, Atlanta, GA USA. [Langston, Amelia] Emory Univ, Bone Marrow & Stem Cell Transplant Ctr, Winship Canc Inst, Atlanta, GA 30322 USA. [Hari, Parameswaran] Med Coll Wisconsin, Div Hematol & Oncol, Sch Med, Milwaukee, WI 53226 USA. [Pulsipher, Michael A.] Univ Utah, Sch Med, Div Hematol Blood & Marrow Transplantat, Salt Lake City, UT USA. [Pulsipher, Michael A.] Primary Childrens Med Ctr, Pediat Blood & Marrow Transplant Program, Huntsman Canc Inst, Salt Lake City, UT 84103 USA. [Bethge, Wolfgang] Univ Tubingen, Sch Med, Tubingen, Germany. [Sahebi, Firoozeh] City Hope Sch Med, Duarte, CA USA. [Bruno, Benedetto] Univ Turin, Sch Med, Turin, Italy. [Maris, Michael B.; McSweeney, Peter A.] Colorado Blood Canc Inst, Denver, CO USA. [Yeager, Andrew] Univ Arizona, Sch Med, Dept Med & Pediat, Tucson, AZ USA. [Petersen, Finn Bo] Intermt Hlth Care, Intermt Blood & Marrow Transplant Acute Leukemia, Salt Lake City, UT USA. [Petersen, Finn Bo] Univ Aarhus, Sch Med, Aarhus, Denmark. [Vindelov, Lars] Rigshosp, Hematopoiet Cell Transplantat Program, Dept Hematol, DK-2100 Copenhagen, Denmark. [McSweeney, Peter A.] Univ Colorado, Sch Med, Boulder, CO 80309 USA. [Huebel, Kai] Univ Cologne, Dept Internal Med, Sch Med, Stem Cell Transplant Program, Cologne, Germany. RP Sorror, ML (reprint author), Fred Hutchinson Canc Res Ctr, Clin Res Div D1 100, 1100 Fairview Ave N, Seattle, WA 98109 USA. EM msorror@fhcrc.org OI Hari, Parameswaran/0000-0002-8800-297X FU Japanese Heath Sciences; Athersys Inc; BMT/CTN; Medac GmbH; Fresenius GmbH; Pfizer; Miltenyi Biotech GmbH; Millennium Pharmaceuticals; Danish Cancer Society; Lundbeck Foundation; Research Council of Rigshospitalet; Region of the Capital of Denmark; National Institutes of Health (NIH) [P01HL036444, P01CA078902, P01CA018029, P30CA015704, R00HL088021]; Leukemia/Lymphoma Society [7008-08] FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Sandmaier reported serving on the board of ArevaMed. Dr Franke reported receiving travel/accommodations/meeting expenses for the European Group of Blood and Marrow Transplantation 2009 meeting. Dr Maziarz reported receiving grants or grants pending (grant money to institution) from Japanese Heath Sciences, Athersys Inc, and BMT/CTN; serving on the speakers bureaus of Millennium Pharmaceuticals Inc and Genzyme Inc; receiving royalties from Springer for publication of a book; and receiving honoraria for lectures (groups change yearly; usually related to community oncology educational efforts). Dr Bethge reported serving as a consultant for Miltenyi Biotech GmbH; receiving grants or grants pending from Medac GmbH, Fresenius GmbH, Pfizer, and Miltenyi Biotech GmbH; receiving payment for lectures from Miltenyi Biotech GmbH; and receiving travel/accommodations/meeting expenses from Medac GmbH. Dr Sahebi reported receiving travel/accommodations/meeting expenses and a research fund from Millennium Pharmaceuticals. Dr Vindelov reported receiving research grants from the Danish Cancer Society, The Lundbeck Foundation, and the Research Council of Rigshospitalet and receiving a travel and research grant from the Region of the Capital of Denmark. No other authors reported disclosures.; Research for this study has been supported by grants from the National Institutes of Health (NIH) (P01HL036444, P01CA078902, P01CA018029, P30CA015704, and R00HL088021) and from the Leukemia/Lymphoma Society (7008-08). NR 38 TC 101 Z9 101 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 2 PY 2011 VL 306 IS 17 BP 1874 EP 1883 DI 10.1001/jama.2011.1558 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 839OD UT WOS:000296376200021 PM 22045765 ER PT J AU Chen, WY Rosner, B Hankinson, SE Colditz, GA Willett, WC AF Chen, Wendy Y. Rosner, Bernard Hankinson, Susan E. Colditz, Graham A. Willett, Walter C. TI Moderate Alcohol Consumption During Adult Life, Drinking Patterns, and Breast Cancer Risk SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PROGESTERONE-RECEPTOR STATUS; POSTMENOPAUSAL WOMEN; PROSPECTIVE COHORT; ESTROGEN; DISEASE; HEALTH; AGE; PREMENOPAUSAL; ASSOCIATION; NUTRITION AB Context Multiple studies have linked alcohol consumption to breast cancer risk, but the risk of lower levels of consumption has not been well quantified. In addition, the role of drinking patterns (ie, frequency of drinking and "binge" drinking) and consumption at different times of adult life are not well understood. Objective To evaluate the association of breast cancer with alcohol consumption during adult life, including quantity, frequency, and age at consumption. Design, Setting, and Participants Prospective observational study of 105 986 women enrolled in the Nurses' Health Study followed up from 1980 until 2008 with an early adult alcohol assessment and 8 updated alcohol assessments. Main Outcome Measures Relative risks of developing invasive breast cancer. Results During 2.4 million person-years of follow-up, 7690 cases of invasive breast cancer were diagnosed. Increasing alcohol consumption was associated with increased breast cancer risk that was statistically significant at levels as low as 5.0 to 9.9 g per day, equivalent to 3 to 6 drinks per week (relative risk, 1.15; 95% CI, 1.06-1.24; 333 cases/100 000 person-years). Binge drinking, but not frequency of drinking, was associated with breast cancer risk after controlling for cumulative alcohol intake. Alcohol intake both earlier and later in adult life was independently associated with risk. Conclusions Low levels of alcohol consumption were associated with a small increase in breast cancer risk, with the most consistent measure being cumulative alcohol intake throughout adult life. Alcohol intake both earlier and later in adult life was independently associated with risk. JAMA. 2011; 306(17): 1884-1890 C1 [Chen, Wendy Y.; Rosner, Bernard; Hankinson, Susan E.; Willett, Walter C.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Chen, Wendy Y.; Rosner, Bernard; Hankinson, Susan E.; Willett, Walter C.] Harvard Univ, Sch Med, Boston, MA USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hankinson, Susan E.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hankinson, Susan E.] Univ Massachusetts, Div Biostat & Epidemiol, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. RP Chen, WY (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM wendy.chen@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU National Institutes of Health [P01 CA87969] FX The work reported herein was supported by the National Institutes of Health (grant P01 CA87969). NR 44 TC 131 Z9 138 U1 3 U2 31 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 2 PY 2011 VL 306 IS 17 BP 1884 EP 1890 DI 10.1001/jama.2011.1590 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 839OD UT WOS:000296376200022 PM 22045766 ER PT J AU Fiore, LD D'Avolio, LW AF Fiore, Louis D. D'Avolio, Leonard William TI Detours on the Road to Personalized Medicine Barriers to Biomarker Validation and Implementation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Fiore, Louis D.; D'Avolio, Leonard William] VA Boston Healthcare Syst, Cooperat Studies Program Coordinating Ctr, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Jamaica Plain, MA USA. [Fiore, Louis D.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Fiore, Louis D.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [D'Avolio, Leonard William] Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. [D'Avolio, Leonard William] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Fiore, LD (reprint author), Boston VA Healthcare Syst, MAVERIC, Jamaica Plain Campus,150 S Huntington Ave, Boston, MA 02130 USA. EM louis.fiore@va.gov NR 7 TC 10 Z9 10 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 2 PY 2011 VL 306 IS 17 BP 1914 EP 1915 DI 10.1001/jama.2011.1605 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 839OD UT WOS:000296376200027 PM 22045770 ER PT J AU Jawa, A Shi, L O'Brien, T Wells, J Higgins, L Macy, J Warner, JJP AF Jawa, Andrew Shi, Lewis O'Brien, Travis Wells, Jessica Higgins, Laurence Macy, John Warner, Jon J. P. TI Prosthesis of Antibiotic-Loaded Acrylic Cement (PROSTALAC) Use for the Treatment of Infection After Shoulder Arthroplasty SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID REPLACEMENT; MANAGEMENT AB Background: There are limited data on Prosthesis of Antibiotic-Loaded Acrylic Cement (PROSTALAC) use for the treatment of infection following shoulder arthroplasty. We performed a retrospective review of our experience with the PROSTALAC in terms of infection eradication, complications, and outcomes. Methods: Twenty-eight patients with an infection at the site of a. shoulder arthroplasty who were managed with the PROSTALAC were followed until eradication of the infection and maximum functional improvement. The average duration of follow-up was 27.6 months (range, twelve to sixty-nine months). In twenty-five of the twenty-eight patients, the PROSTALAC was created with antibiotic-impregnated cement, a standard humeral head mold, and a scaffold with either a one-third tubular plate or a 3.5-mm reconstruction plate. Three PROSTALAC implants had no scaffold. Results: Although all patients benefited from the Use of the PROSTALAC, there were nine complications in eight patients (29%), with six additional unplanned surgical procedures being performed in this group. One patient had a dislocation, three had a fracture of the PROSTALAC, and five had recurrent infections requiring debridement and revision PROSTALAC placement. All fractures were associated with use of the semitubular plate. Twelve patients (43%), including two with revision PROSTALAC implants, were satisfied with pain relief and function and declined a second-stage procedure. With the exclusion of two patients who had a revision PROSTALAC implant, sixteen patients (57%) had a second-stage procedure; the procedures included ten reverse shoulder arthroplasties, three hemiarthroplasties, two total shoulder arthroplasties, and one resection arthroplasty. At the time of the latest follow-up, the average forward elevation of the shoulder was 77 degrees (range, 30 degrees to 130 degrees). Fifteen patients had no or mild pain, eight patients had moderate pain, and five had severe pain. Patients with reverse total shoulder arthroplasties did not have improved function compared with the other cohorts. Conclusions: The use of the PROSTALAC for the treatment of infection following shoulder arthroplasty is beneficial. Infection was initially eradicated in twenty-three (82%) of twenty-eight patients, more than half of our patients had mild or no pain, and 43 of patients declined a second-stage procedure because of acceptable function and pain relief. Conversely, five of twenty-eight patients had severe pain and five patients had persistent infection requiring additional surgery. The use of the reverse total shoulder arthroplasty did not appear to improve outcomes. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. C1 Massachusetts Gen Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Vermont, Med Ctr, Burlington, VT 05401 USA. RP Jawa, A (reprint author), Boston Univ, Med Ctr, Dept Orthopaed Surg, 850 Harrison Ave,Dowling Bldg,2 North, Boston, MA 02118 USA. EM Andrew.Jawa@bmc.org NR 11 TC 8 Z9 8 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD NOV 2 PY 2011 VL 93A IS 21 BP 2001 EP 2009 DI 10.2106/JBJS.J.00833 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 840ZZ UT WOS:000296482800007 PM 22048095 ER PT J AU Guitton, TG Ring, D AF Guitton, Thierry G. Ring, David CA Sci Variation Grp TI Interobserver Reliability of Radial Head Fracture Classification: Two-Dimensional Compared with Three-Dimensional CT SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID COMPUTED-TOMOGRAPHY; AGREEMENT AB Background:, The Broberg and Morrey modification of the Mason classification of radial head fractures has substantial interobserver variation. This study used a large. web-based collaborative of experienced orthopaedic surgeons to test the. hypothesis that three-dimensional reconstructions of computed tomography (CT) scans improve the interobserver reliability of the classification of radial head fractures according to the Broberg and Morrey modification of the Mason classification. Methods: Eighty-five orthopaedic surgeons evaluated twelve radial head fractures. They were randomly assigned to review either radiographs and two-dimensional CT scans or radiographs and three-dimensional CT images to determine the fracture Classification, fracture characteristics, and treatment recommendations. The kappa multirater measure (kappa) was calculated to estimate agreement between observers. Results: Three-dimensional CT had moderate agreement and two-dimensional CT had fair agreement among observers for the Broberg and Morrey modification of the Mason classification, a difference that was significant. Observers assessed seven fracture characteristics, including fracture line, comminution, articular surface involvement, articular step or gap of >= 2 mm, central impaction, recognition of more than three fracture fragments, and fracture fragments too small to repair. There was a significant difference in kappa values between three-dimensional CT and two-dimensional CT for fracture fragments too small to repair, recognition of three fracture fragments, and central impaction. The difference between the other four fracture characteristics was not significant. Among treatment recommendations, there was fair agreement for both three-dimensional CT and two-dimensional CT. Conclusions: Although three-dimensional CT led to some small but significant decreases in interobserver variation, there is still considerable disagreement regarding classification and characterization of radial head fractures. Three-dimensional CT may be insufficient to optimize interobserver agreement. C1 [Guitton, Thierry G.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. RP Guitton, TG (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org RI Page, Richard/K-6327-2015; OI Page, Richard/0000-0002-2225-7144; van der Heide, Huub JL/0000-0003-3910-5048; Frihagen, Frede/0000-0002-4811-669X; Ladd, Amy/0000-0003-0948-1034; Guitton, Thierry/0000-0002-2599-1985; Soong, Maximillian/0000-0003-0333-8181 NR 15 TC 26 Z9 29 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD NOV 2 PY 2011 VL 93A IS 21 BP 2015 EP 2021 DI 10.2106/JBJS.J.00711 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 840ZZ UT WOS:000296482800009 PM 22048097 ER PT J AU Watkins, N Irimia, D Toner, M Bashir, R AF Watkins, Nicholas Irimia, Daniel Toner, Mehmet Bashir, Rashid TI On a Chip SO IEEE PULSE LA English DT Article ID CIRCULATING TUMOR-CELLS; ON-A-CHIP; GRADIENTS; CHEMOTAXIS; BIOSENSORS; BLOOD C1 [Watkins, Nicholas; Bashir, Rashid] Univ Illinois, Dept Elect & Comp Engn & Bioengn, Bioengn & Micro & Nanotechnol Lab, Urbana, IL USA. [Irimia, Daniel; Toner, Mehmet] Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. [Irimia, Daniel; Toner, Mehmet] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Boston, MA 02114 USA. [Irimia, Daniel; Toner, Mehmet] Harvard Univ, Sch Med, Boston, MA USA. RP Watkins, N (reprint author), Univ Illinois, Dept Elect & Comp Engn & Bioengn, Bioengn & Micro & Nanotechnol Lab, Urbana, IL USA. EM watkins7@illinois.edu; rbashir@illinois.edu; dirimia@hms.harvard.edu; mtoner@hms.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU NCI NIH HHS [R01 CA120003, R25 CA154015]; NIBIB NIH HHS [P41 EB002503]; NIGMS NIH HHS [R01 GM092804] NR 32 TC 6 Z9 6 U1 0 U2 15 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2154-2287 J9 IEEE PULSE JI IEEE Pulse PD NOV-DEC PY 2011 VL 2 IS 6 BP 19 EP 27 DI 10.1109/MPUL.2011.942762 PG 9 WC Engineering, Biomedical SC Engineering GA 992UF UT WOS:000307804500008 PM 22147065 ER PT J AU Seker, E Sung, JH Shuler, ML Yarmush, ML AF Seker, Erkin Sung, Jong Hwan Shuler, Michael L. Yarmush, Martin L. TI Solving Medical Problems with BioMEMS SO IEEE PULSE LA English DT Article ID FLUID SHEAR-STRESS; LIVING CELL ARRAY; MICROFLUIDIC SYSTEMS; GRADIENTS; CULTURE; CHIP; DIFFERENTIATION; STIMULATION; GENERATION; CHEMOTAXIS C1 [Seker, Erkin] Harvard Univ, Sch Med, Ctr Engn Med, Boston, MA 02115 USA. [Seker, Erkin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Seker, Erkin] Univ Calif Davis, Dept Elect & Comp Engn, Davis, CA 95616 USA. [Sung, Jong Hwan] Hongik Univ, Dept Chem Engn, Seoul, South Korea. [Shuler, Michael L.] Cornell Univ, Dept Biomed Engn, Ithaca, NY USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Seker, E (reprint author), Harvard Univ, Sch Med, Ctr Engn Med, Boston, MA 02115 USA. EM eseker@ucdavis.edu; jhsung22@hongik.ac.kr; mls50@cornell.edu; ireis@sbi.org OI Seker, Erkin/0000-0003-2401-3562 FU National Institutes of Health [AI063795, EB002503]; Massachusetts General Hospital Fund for Medical Discovery award [217035]; National Research Foundation of Korea award [2011-0013862]; Hongik University new faculty research support fund; Army Corps of Engineers (CERL) [W9132T-0] FX Michael L. Shuler acknowledges support from the National Institutes of Health awards AI063795 and EB002503, Erkin Seker from the Massachusetts General Hospital Fund for Medical Discovery award 217035, Jong Hwan Sung from the National Research Foundation of Korea award 2011-0013862 and support from Hongik University new faculty research support fund, and Michael L. Shuler acknowledges partial support from the Army Corps of Engineers (CERL) W9132T-0. The first two authors, Erkin Seker and Jong Hwan Sung, contributed equally to this work. NR 54 TC 1 Z9 1 U1 0 U2 11 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2154-2287 J9 IEEE PULSE JI IEEE Pulse PD NOV-DEC PY 2011 VL 2 IS 6 BP 51 EP 59 DI 10.1109/MPUL.2011.942928 PG 9 WC Engineering, Biomedical SC Engineering GA 992UF UT WOS:000307804500012 PM 22147069 ER PT J AU Patti, JA AF Patti, John A. TI The Challenges of Leadership in the New Era of Health Care SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Patti, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM jpatti@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD NOV PY 2011 VL 8 IS 11 BP 739 EP 740 DI 10.1016/j.jacr.2011.09.017 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 971KF UT WOS:000306202100001 PM 22051451 ER PT J AU Rosen, MP Ding, A Blake, MA Baker, ME Cash, BD Fidler, JL Grant, TH Greene, FL Jones, B Katz, DS Lalani, T Miller, FH Small, WC Spottswood, S Sudakoff, GS Tulchinsky, M Warshauer, DM Yee, J Coley, BD AF Rosen, Max P. Ding, Alexander Blake, Michael A. Baker, Mark E. Cash, Brooks D. Fidler, Jeff L. Grant, Thomas H. Greene, Frederick L. Jones, Bronwyn Katz, Douglas S. Lalani, Tasneem Miller, Frank H. Small, William C. Spottswood, Stephanie Sudakoff, Gary S. Tulchinsky, Mark Warshauer, David M. Yee, Judy Coley, Brian D. TI ACR Appropriateness Criteria (R) Right Lower Quadrant Pain-Suspected Appendicitis SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness criteria; CT; ultrasound; appendicitis; abdominal pain; comparative studies ID COMPUTED-TOMOGRAPHY SCAN; NEGATIVE APPENDECTOMY; PERFORATION RATES; PREGNANT PATIENTS; HELICAL CT; DIAGNOSTIC PERFORMANCE; CONTRAST MATERIAL; RECTAL CONTRAST; ABDOMINAL-PAIN; CHILDREN AB The diagnostic imaging of patients presenting with right lower quadrant pain and suspected appendicitis may be organized according to age and gender and to the presence or absence of "classic" signs and symptoms of acute appendicitis. Among adult patients presenting with clinical signs of acute appendicitis, the sensitivity and specificity of CT are greater than those of ultrasound, with improved performance when CT is performed with intravenous contrast. The use of rectal contrast has been associated with decreased time in the emergency department. Computed tomography has also been shown to reduce cost and negative appendectomy rates. Both CT and ultrasound are also effective in the identification of causes of right lower quadrant pain unrelated to appendicitis. Among pediatric patients, the sensitivity and specificity of graded-compression ultrasound can approach those of CT, without the use of ionizing radiation. Performing MRI after inconclusive ultrasound in pregnant patients has been associated with sensitivity and specificity of 80% to 86% and 97% to 99%, respectively. The ACR Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Rosen, Max P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ding, Alexander; Blake, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Baker, Mark E.] Cleveland Clin, Cleveland, OH 44106 USA. [Cash, Brooks D.] Natl Naval Med Ctr, Bethesda, MD USA. [Cash, Brooks D.] Amer Gastroenterol Assoc, Bethesda, MD USA. [Fidler, Jeff L.] Mayo Clin, Rochester, MN USA. [Grant, Thomas H.] NW Med Fac, Chicago, IL USA. [Greene, Frederick L.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Greene, Frederick L.] Amer Coll Surg, Chicago, IL USA. [Jones, Bronwyn] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Katz, Douglas S.] Winthrop Univ Hosp, Mineola, NY 11501 USA. [Lalani, Tasneem] Inland Imaging Associates, Seattle, WA USA. [Lalani, Tasneem] Univ Washington, Seattle, WA 98195 USA. [Miller, Frank H.] Northwestern Univ, Feinberg Sch Med, NMH, Chicago, IL 60611 USA. [Small, William C.] Emory Univ, Atlanta, GA 30322 USA. [Spottswood, Stephanie] Vanderbilt Childrens Hosp, Nashville, TN USA. [Spottswood, Stephanie; Tulchinsky, Mark] Soc Nucl Med, Reston, VA USA. [Sudakoff, Gary S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Tulchinsky, Mark] Milton S Hershey Med Ctr, Hershey, PA USA. [Warshauer, David M.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Yee, Judy] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Coley, Brian D.] Nationwide Childrens Hosp, Columbus, OH USA. RP Rosen, MP (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM mrosen2@bidmc.harvard.edu NR 56 TC 64 Z9 65 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD NOV PY 2011 VL 8 IS 11 BP 749 EP 755 DI 10.1016/j.jacr.2011.07.010 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 971KF UT WOS:000306202100006 PM 22051456 ER PT J AU Hawkins, CM Krishnaraj, A AF Hawkins, C. Matthew Krishnaraj, Arun TI Resident and Fellow State Chapters: Providing Impact From the Local Level SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Krishnaraj, Arun] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Hawkins, C. Matthew] Univ Cincinnati, Coll Med, Dept Radiol, Cincinnati, OH 45221 USA. RP Krishnaraj, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. EM hawkcm@gmail.com; akrishnaraj@partners.org NR 1 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD NOV PY 2011 VL 8 IS 11 BP 812 EP 813 DI 10.1016/j.jacr.2011.06.004 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 971KF UT WOS:000306202100019 PM 22051469 ER PT J AU Hoang, T Byers, AL Barnes, D Cawthon, PM Yaffe, K AF Hoang, T. Byers, A. L. Barnes, D. Cawthon, P. M. Yaffe, K. TI ALCOHOL CONSUMPTION OVER THE LIFE COURSE AND COGNITIVE OUTCOMES IN OLDER WOMEN SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hoang, T.; Byers, A. L.; Barnes, D.; Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Byers, A. L.; Barnes, D.; Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cawthon, P. M.] Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, San Francisco, CA USA. [Yaffe, K.] Univ Calif San Francisco, Dept Neurol, Dept Epidemiol & Biostat, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 20 EP 20 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602000094 ER PT J AU Spira, AP Covinsky, K Rebok, G Punjabi, N Stone, KL Hillier, TA Ensrud, K Yaffe, K AF Spira, A. P. Covinsky, K. Rebok, G. Punjabi, N. Stone, K. L. Hillier, T. A. Ensrud, K. Yaffe, K. TI OBJECTIVELY MEASURED SLEEP AND FUNCTIONAL DECLINE IN OLDER WOMEN SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Spira, A. P.; Rebok, G.; Punjabi, N.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Covinsky, K.; Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Covinsky, K.; Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Punjabi, N.] Johns Hopkins Sch Med, Baltimore, MD USA. [Stone, K. L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Hillier, T. A.] Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. [Ensrud, K.] Minneapolis VAMC, Minneapolis, MN USA. [Ensrud, K.] Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 20 EP 20 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602000093 ER PT J AU Brady, CB Kaiser, AP Spiro, A AF Brady, C. B. Kaiser, A. Pless Spiro, A. TI COMBAT-RELATED STRESS SYMPTOMS IN AGING VETERANS: DISTINCT SUBGROUPS OR POINTS ON A CONTINUUM? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Brady, C. B.; Kaiser, A. Pless; Spiro, A.] VA Boston Healthcare Syst, Boston, MA USA. [Brady, C. B.; Kaiser, A. Pless] Boston Univ, Sch Med, Boston, MA 02118 USA. [Spiro, A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 21 EP 21 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602000099 ER PT J AU Hilgeman, MM Archambault, E Billings, RL Gosian, J Karel, M Moye, J AF Hilgeman, M. M. Archambault, E. Billings, R. L. Gosian, J. Karel, M. Moye, J. TI FROM COMBAT TO CANCER: RISK AND RESILIENCY IN VETERAN CANCER SURVIVORS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hilgeman, M. M.] Tuscaloosa VA Med Ctr, Tuscaloosa, AL USA. [Archambault, E.; Gosian, J.; Karel, M.; Moye, J.] VA Boston Healthcare Syst, Boston, MA USA. [Archambault, E.; Karel, M.; Moye, J.] Harvard Univ, Sch Med, Boston, MA USA. [Billings, R. L.] Northshore Psychol Associates LLC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 21 EP 22 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602000100 ER PT J AU Park, C Kaiser, AP King, D King, L Spiro, A AF Park, C. Kaiser, A. Pless King, D. King, L. Spiro, A. TI WAR-TIME CAPTIVITY: DOES RESILIENCE MODERATE ITS IMPACT ON WELL-BEING ACROSS THE LIFE COURSE? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Park, C.] Univ Connecticut, Storrs, CT USA. [Kaiser, A. Pless; King, D.; King, L.; Spiro, A.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 21 EP 21 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602000098 ER PT J AU Sanders, J Fitzpatrick, A Boudreau, R Arnold, A Aviv, A Fried, LF Harris, TB Newman, AB AF Sanders, J. Fitzpatrick, A. Boudreau, R. Arnold, A. Aviv, A. Fried, L. F. Harris, T. B. Newman, A. B. TI LEUKOCYTE TELOMERE LENGTH IS ASSOCIATED WITH AGE-RELATED CHRONIC DISEASE BURDEN IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Sanders, J.; Boudreau, R.; Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA USA. [Fitzpatrick, A.; Arnold, A.] Univ Washington, Seattle, WA 98195 USA. [Aviv, A.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [Fried, L. F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Harris, T. B.] NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 22 EP 23 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602000105 ER PT J AU Hilgeman, MM Snow, A Mahaney-Price, AF Kertesz, S Davis, L AF Hilgeman, M. M. Snow, A. Mahaney-Price, A. F. Kertesz, S. Davis, L. TI EXAMINATION OF THE MONTREAL COGNITIVE ASSESSMENT (MOCA): FINDINGS FROM THE ALABAMA VETERANS RURAL HEALTH INITIATIVE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hilgeman, M. M.; Snow, A.; Mahaney-Price, A. F.; Davis, L.] Tuscaloosa VA Med Ctr, Tuscaloosa, AL USA. [Kertesz, S.] Birmingham VA Med Ctr, Birmingham, AL USA. [Kertesz, S.] Univ Alabama Birmingham, Birmingham, AL USA. [Davis, L.] Univ Alabama, Sch Med, Tuscaloosa, AL 35401 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 31 EP 32 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602000149 ER PT J AU Bolkan, C Bonner, L Campbell, DG Lanto, A Rubenstein, L Chaney, E AF Bolkan, C. Bonner, L. Campbell, D. G. Lanto, A. Rubenstein, L. Chaney, E. TI THE COMPLEX RELATIONSHIP BETWEEN SOCIAL SUPPORT AND DEPRESSION: THE SIGNIFICANCE OF PATIENT SATISFACTION AND MEDICATION ADHERENCE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Bolkan, C.] Washington State Univ, Vancouver, WA USA. [Bonner, L.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Campbell, D. G.] Univ Montana, Missoula, MT 59812 USA. [Lanto, A.; Rubenstein, L.] VA Greater Angeles Healthcare Syst, Dept Vet Affairs, Hlth Serv Res & Dev Ctr Excellence, Los Angeles, CA USA. [Rubenstein, L.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Rubenstein, L.] RAND Hlth Program, Santa Monica, CA USA. [Chaney, E.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 34 EP 34 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602000159 ER PT J AU Kresevic, DM Burant, CJ Denton, JE Ibrahim, S AF Kresevic, D. M. Burant, C. J. Denton, J. E. Ibrahim, S. TI OUTPATIENT ANTICOAGULATION EDUCATION AND OUTCOMES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kresevic, D. M.; Burant, C. J.; Denton, J. E.] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Kresevic, D. M.] Univ Hosp, Case Med Ctr, Cleveland, OH USA. [Kresevic, D. M.; Burant, C. J.] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA. [Ibrahim, S.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 74 EP 74 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602000332 ER PT J AU Hughes, J Martin, JL AF Hughes, J. Martin, J. L. TI SLEEP: AN OVERLOOKED COMPONENT OF HEALTH AND QUALITY OF LIFE IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hughes, J.; Martin, J. L.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, North Hills, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 78 EP 78 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602000348 ER PT J AU Vitiello, MV Baker, LD Borson, S Friedman, SD Barsness, S Merriam, GR AF Vitiello, M. V. Baker, L. D. Borson, S. Friedman, S. D. Barsness, S. Merriam, G. R. TI TESAMORELIN, A HUMAN GROWTH HORMONE RELEASING HORMONE ANALOGUE, IMPROVES COGNITIVE FUNCTION IN MCI AND HEALTHY AGING: RESULTS OF A RANDOMIZED PLACEBO-CONTROLLED TRIAL SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Vitiello, M. V.; Baker, L. D.; Borson, S.; Barsness, S.; Merriam, G. R.] Univ Washington, Seattle, WA 98195 USA. [Friedman, S. D.] Childrens Hosp, Seattle, WA USA. [Merriam, G. R.] VA Puget Sound Hlth Care Syst, Tacoma, WA USA. [Merriam, G. R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 106 EP 106 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602000481 ER PT J AU Wittich, AR Williams, BR Woodby, LL Burgio, KL AF Wittich, A. R. Williams, B. R. Woodby, L. L. Burgio, K. L. TI "THE WHOLE POWER OF ATTORNEY": UNDERSTANDING ADVANCE DIRECTIVES AMONG NEXT-OF-KIN IN VA MEDICAL CENTERS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Wittich, A. R.; Williams, B. R.; Woodby, L. L.; Burgio, K. L.] Birmingham VAMC, Birmingham, AL USA. [Williams, B. R.; Woodby, L. L.; Burgio, K. L.] Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 136 EP 137 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602000623 ER PT J AU Mavandadi, S Mamikonyan, E Duda, JE Weintraub, D AF Mavandadi, S. Mamikonyan, E. Duda, J. E. Weintraub, D. TI INTERPERSONAL FUNCTIONING IN PARKINSON'S DISEASE: A DYADIC ANALYSIS OF VETERANS AND CAREGIVERS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mavandadi, S.; Weintraub, D.] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Mavandadi, S.; Mamikonyan, E.; Weintraub, D.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Duda, J. E.; Weintraub, D.] Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Duda, J. E.] Univ Penn, Dept Neurol, Penn Hosp, Parkinsons Dis & Movement Disorders Ctr, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 141 EP 141 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602000643 ER PT J AU Mills, WL Regev, T Kunik, ME Wilson, NL Moye, J McCullough, LB Naik, AD AF Mills, W. L. Regev, T. Kunik, M. E. Wilson, N. L. Moye, J. McCullough, L. B. Naik, A. D. TI A SCREENING TOOL FOR CAPACITY TO LIVE SAFELY AND INDEPENDENTLY IN THE COMMUNITY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mills, W. L.; Kunik, M. E.; Wilson, N. L.; Naik, A. D.] Michael E DeBakey VA Med Ctr, Houston Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Mills, W. L.; Kunik, M. E.; Wilson, N. L.; McCullough, L. B.; Naik, A. D.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Regev, T.] Harris Cty Hosp Dist, Quentin Mease Community Hosp, Houston, TX USA. [Kunik, M. E.] Michael E DeBakey VA Med Ctr, Vet Affairs S Cent Mental Illness Res Educ & Clin, Houston, TX USA. [Moye, J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Moye, J.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 168 EP 168 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602001076 ER PT J AU Tennstedt, SL Volandes, A Welch, L AF Tennstedt, S. L. Volandes, A. Welch, L. TI AN INTERACTIVE DECISION AID TO FACILITATE THE PROCESS OF ADVANCE CARE PLANNING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Tennstedt, S. L.; Welch, L.] New England Res Inst, Watertown, MA 02172 USA. [Volandes, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 172 EP 173 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602001096 ER PT J AU Mahaney-Price, AF Hilgeman, MM Kertesz, S Davis, L AF Mahaney-Price, A. F. Hilgeman, M. M. Kertesz, S. Davis, L. TI RURAL ALABAMA VETERAN ADVANCE DIRECTIVE BEHAVIOR AND DESIRE FOR HELP COMPLETING AN ADVANCE DIRECTIVE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mahaney-Price, A. F.; Hilgeman, M. M.; Davis, L.] Tuscaloosa VA Med Ctr, Tuscaloosa, AL USA. [Kertesz, S.] Birmingham VA Med Ctr, Birmingham, AL USA. [Davis, L.] Univ Alabama, Sch Med, Tuscaloosa, AL 35401 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 174 EP 174 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602001103 ER PT J AU Wolden-Hanson, T AF Wolden-Hanson, T. TI HYPOTHALAMIC CONTROL OF THE ANOREXIA OF AGING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Wolden-Hanson, T.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Wolden-Hanson, T.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 188 EP 188 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602001162 ER PT J AU Kramer, B Barczi, S Chernoff, R Horvath, KJ Howe, JL Huh, J Tumosa, N Saunders, MJ AF Kramer, B. Barczi, S. Chernoff, R. Horvath, K. J. Howe, J. L. Huh, J. Tumosa, N. Saunders, M. J. TI THE VA GERIATRIC SCHOLARS PROGRAM: ENHANCING SKILLS IN RURAL PRIMARY CARE SETTINGS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kramer, B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Kramer, B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Horvath, K. J.] Bedford GRECC, Boston, MA USA. [Barczi, S.] Madison GRECC, Madison, WI USA. [Huh, J.] Palo Alto GRECC, Palo Alto, CA USA. [Saunders, M. J.] San Antonio GRECC, San Antonio, TX USA. [Tumosa, N.] St Louis GRECC, St Louis, MO USA. [Chernoff, R.] Birmingham GRECC, Birmingham, AL USA. [Howe, J. L.] Bronx GRECC, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 204 EP 204 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602001244 ER PT J AU Moye, J Danhauer, SC Chapman, J Doherty, KM White, C AF Moye, J. Danhauer, S. C. Chapman, J. Doherty, K. M. White, C. TI OBSTACLES AND INROADS TO YOGA FOR OLDER VETERAN CANCER SURVIVORS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Moye, J.; Doherty, K. M.] VA Boston Healthcare Syst, Mental Hlth, Brockton, MA USA. [Danhauer, S. C.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Chapman, J.] Hands Hlth, San Francisco, CA USA. [White, C.] Michael E Debakey VA VA Med Ctr, Houston, TX USA. [Moye, J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 223 EP 223 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602001343 ER PT J AU Ramsey, J Neupert, SD Mroczek, D Spiro, A AF Ramsey, J. Neupert, S. D. Mroczek, D. Spiro, A. TI EMOTIONAL COMPLEXITY MODERATES AGE DIFFERENCES IN REACTIVITY TO DAILY HEALTH STRESSORS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Ramsey, J.; Neupert, S. D.] N Carolina State Univ, Raleigh, NC 27695 USA. [Mroczek, D.] Purdue Univ, W Lafayette, IN 47907 USA. [Spiro, A.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 225 EP 225 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602001353 ER PT J AU Anderson, R AF Anderson, R. TI IMPACT OF CALORIE RESTRICTION (CR) ON CELLULAR ASPECTS OF METABOLIC DECLINE IN AGING RHESUS SKELETAL MUSCLE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Anderson, R.] Univ Wisconsin, Madison, WI USA. [Anderson, R.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 242 EP 242 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602001441 ER PT J AU Forman, D Allsup, K Zavin, A Lazzari, A Lecker, S Joseph, J Arena, R AF Forman, D. Allsup, K. Zavin, A. Lazzari, A. Lecker, S. Joseph, J. Arena, R. TI HANDGRIP STRENGTH REFLECTS DECREASED LEAN TISSUE AND FUNCTION IN ELDERLY HEART FAILURE PATIENTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Forman, D.; Allsup, K.; Zavin, A.; Lazzari, A.; Joseph, J.] VA Boston Healthcare Syst, Boston, MA USA. [Forman, D.; Lecker, S.; Joseph, J.] Harvard Univ, Sch Med, Boston, MA USA. [Lazzari, A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Arena, R.] Univ New Mexico, Albuquerque, NM 87131 USA. RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 267 EP 267 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602001575 ER PT J AU Kelly, B Karel, M Moye, J Archambault, E Noecker, TL Kaiser, AP AF Kelly, B. Karel, M. Moye, J. Archambault, E. Noecker, T. L. Kaiser, A. Pless TI MENTAL HEALTH SYMPTOMS AND PATIENT SATISFACTION IN A VA GERIATRIC MENTAL HEALTH CLINIC SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kelly, B.; Karel, M.; Moye, J.; Archambault, E.; Noecker, T. L.; Kaiser, A. Pless] VA Boston Healthcare Syst, Boston, MA USA. [Karel, M.; Moye, J.; Noecker, T. L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Noecker, T. L.; Kaiser, A. Pless] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 270 EP 270 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602001588 ER PT J AU Garcia, C Espinoza, SE Hazuda, HP AF Garcia, C. Espinoza, S. E. Hazuda, H. P. TI LEVELS OF HEALTH LITERACY AMONG HISPANIC ELDERLY PATIENTS AND THEIR CAREGIVERS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Garcia, C.; Espinoza, S. E.; Hazuda, H. P.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Espinoza, S. E.; Hazuda, H. P.] S Texas Vet Healthcare Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 283 EP 283 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602001643 ER PT J AU Pasinetti, GM AF Pasinetti, G. M. TI THE ROLE OF NUTRI-EPIGENETICS AND PERSONALIZED MEDICINE IN DIETARY LIFESTYLE CHOICES IN ALZHEIMER'S DISEASE SO GERONTOLOGIST LA English DT Meeting Abstract C1 Mt Sinai Sch Med, New York, NY USA. James J Peters Vet Affairs Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 296 EP 296 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602001704 ER PT J AU Espinoza, SE Hazuda, HP AF Espinoza, S. E. Hazuda, H. P. TI ETHNIC DIFFERENCE IN PERFORMANCE-BASED MEASURES OF BASIC AND INSTRUMENTAL ACTIVITIES OF DAILY LIVING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Espinoza, S. E.; Hazuda, H. P.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Espinoza, S. E.; Hazuda, H. P.] S Texas Vet Healthcare Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 308 EP 309 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602002041 ER PT J AU Sullivan, JL Shwartz, M Gerena-Melia, M Berlowitz, D Burgess, J AF Sullivan, J. L. Shwartz, M. Gerena-Melia, M. Berlowitz, D. Burgess, J. TI EXAMINING THE RELATIONSHIP BETWEEN A MINIMUM DATA SET COMPOSITE QUALITY INDICATOR AND THE ARTIFACTS OF CULTURE CHANGE TOOL SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Sullivan, J. L.; Shwartz, M.; Gerena-Melia, M.; Burgess, J.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Berlowitz, D.] Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Sullivan, J. L.; Shwartz, M.; Berlowitz, D.; Burgess, J.] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 327 EP 327 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602002121 ER PT J AU Milberg, W McGlinchey, R Leritz, E Salat, D Zade, D Rudolph, JL AF Milberg, W. McGlinchey, R. Leritz, E. Salat, D. Zade, D. Rudolph, J. L. TI CEREBROVASCULAR RISK, DECISION MAKING, AND THE BRAIN: A CRITICAL CONNECTION TO THE MAINTENANCE OF HEALTH IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Milberg, W.; McGlinchey, R.; Leritz, E.; Salat, D.; Zade, D.; Rudolph, J. L.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 347 EP 348 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602002224 ER PT J AU Atri, A Mitchell, M AF Atri, A. Mitchell, M. TI COGNITIVE ACTIVITY AND REDUCED RISK FOR COGNITIVE DECLINE AND ALZHEIMER'S DISEASE: TRUTH OR MYTH? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Atri, A.; Mitchell, M.] Bedford VA Med Ctr, GRECC, Bedford, MA USA. [Atri, A.; Mitchell, M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Atri, A.; Mitchell, M.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 348 EP 348 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602002227 ER PT J AU Kowall, N Dedeoglu, A AF Kowall, N. Dedeoglu, A. TI DOES EXERCISE ENHANCE PHARMACOTHERAPY IN TRANSGENIC MOUSE MODELS OF AGE-RELATED NEURODEGENERATION? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kowall, N.; Dedeoglu, A.] VA Boston Healthcare, GRECC, Boston, MA USA. [Kowall, N.; Dedeoglu, A.] Boston Univ, Sch Med, Boston, MA 02118 USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 348 EP 348 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602002226 ER PT J AU Rudolph, JL Grande, LJ McGlinchey, R Chester, JG Milberg, W AF Rudolph, J. L. Grande, L. J. McGlinchey, R. Chester, J. G. Milberg, W. TI COGNITIVE THEN FUNCTIONAL IMPAIRMENT OR VISA VERSA: THE CLOCK IN THE BOX EXPERIENCE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Rudolph, J. L.; Grande, L. J.; McGlinchey, R.; Milberg, W.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Chester, J. G.] Albert Einstein Coll Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 348 EP 348 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602002225 ER PT J AU Jones, LI Kramer, J Chernoff, R Howe, JL Francisco, F AF Jones, L. I. Kramer, J. Chernoff, R. Howe, J. L. Francisco, F. TI CREATING A LEARNING COMMUNITY AND WEBINAR SERIES FOR CLINICIANS WORKING WITH OLDER VETERANS IN RURAL SETTINGS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kramer, J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Howe, J. L.; Francisco, F.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA. [Howe, J. L.; Francisco, F.] James J Peters VAMC, VISN GRECC 3, Bronx, NY USA. [Chernoff, R.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Chernoff, R.] Cent Arkansas Vet Healthcare Syst Little Rock GRE, Little Rock, AR USA. [Jones, L. I.; Kramer, J.] VA Greater Los Angeles Healthcare Syst Greater Lo, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 374 EP 374 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602002363 ER PT J AU Kramer, J Harker, JO Mitchell, M Rubenstein, L AF Kramer, J. Harker, J. O. Mitchell, M. Rubenstein, L. TI INSTEP: MAJOR RESEARCH QUESTIONS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kramer, J.] Univ Calif Los Angeles, David Geffen Sch Med, GRECC, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. [Mitchell, M.] Ctr Study Healthcare Provider Behav, Dept Vet Affairs, Sepulveda, CA USA. [Rubenstein, L.] Univ Oklahoma, Reynolds Dept Geriatr Med, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 377 EP 378 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602002379 ER PT J AU Semla, T Damron-Rodriguez, J Berger, S Goodwin, C Beizer, J AF Semla, T. Damron-Rodriguez, J. Berger, S. Goodwin, C. Beizer, J. TI THE RATIONALE AND DEVELOPMENT PROCESS FOR THE PHA MULTIDISCIPLINARY COMPETENCIES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Semla, T.] US Dept Vet Affairs, PBM, Evanston, IL USA. [Semla, T.] Northwestern Univ, Chicago, IL 60611 USA. [Damron-Rodriguez, J.] UCLA Sch Publ Affairs, Los Angeles, CA USA. [Berger, S.] Boston Univ, Coll Hlth & Rehabil Sci, Boston, MA 02215 USA. [Goodwin, C.] Amer Geriatr Soc, New York, NY USA. [Beizer, J.] St Johns Coll Pharmcy, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 377 EP 377 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602002375 ER PT J AU Garrido, MM Penrod, JD AF Garrido, M. M. Penrod, J. D. TI DEPRESSION AND ANXIETY ASSESSMENT AND TREATMENT IN VETERANS RECEIVING PALLIATIVE CARE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Garrido, M. M.; Penrod, J. D.] James J Peters VA Med Ctr, Bronx, NY USA. [Garrido, M. M.; Penrod, J. D.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 388 EP 388 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602002436 ER PT J AU Spira, AP Covinsky, K Rebok, G Stone, KL Redline, S Punjabi, N Yaffe, K AF Spira, A. P. Covinsky, K. Rebok, G. Stone, K. L. Redline, S. Punjabi, N. Yaffe, K. TI OBJECTIVELY MEASURED SLEEP FRAGMENTATION AND NURSING HOME PLACEMENT IN OLDER WOMEN SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Spira, A. P.; Rebok, G.; Punjabi, N.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Covinsky, K.; Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Covinsky, K.; Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Stone, K. L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Redline, S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Punjabi, N.] Johns Hopkins Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 398 EP 398 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602002490 ER PT J AU Roberge, BJ Feldmannova, M Hesse, KA AF Roberge, B. J. Feldmannova, M. Hesse, K. A. TI CHARACTERIZING EMERGENCY DEPARTMENT UTILIZATION PATTERNS FROM A GERIATRIC PRIMARY CARE PRACTICE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Roberge, B. J.; Feldmannova, M.; Hesse, K. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 431 EP 431 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602002658 ER PT J AU Beverly, EA Lee, Y Brooks, KM Hultgren, BA Bishop, JS Ganda, OP Munshi, M Weinger, K AF Beverly, E. A. Lee, Y. Brooks, K. M. Hultgren, B. A. Bishop, J. S. Ganda, O. P. Munshi, M. Weinger, K. TI BENEFITS OF GROUP DIABETES EDUCATION FOR OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Beverly, E. A.; Lee, Y.; Brooks, K. M.; Hultgren, B. A.; Bishop, J. S.; Ganda, O. P.; Munshi, M.; Weinger, K.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Beverly, E. A.; Ganda, O. P.; Munshi, M.; Weinger, K.] Harvard Univ, Sch Med, Boston, MA USA. [Ganda, O. P.; Munshi, M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 440 EP 440 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602002705 ER PT J AU Archambault, E Randazzo, R Wilson, NL Kunik, ME Bass, DM Judge, K Looman, WJ Moye, J AF Archambault, E. Randazzo, R. Wilson, N. L. Kunik, M. E. Bass, D. M. Judge, K. Looman, W. J. Moye, J. TI TRAINING FOR TELEPHONE ADMINISTERED DEMENTIA CARE COORDINATION: LESSONS LEARNED SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Archambault, E.; Moye, J.] VA Boston Healthcare Syst, Geriatr Mental Hlth, Brockton, MA USA. [Randazzo, R.] Massachusetts Alzheimers Assoc, Watertown, MA USA. [Wilson, N. L.; Kunik, M. E.] MEDVAMC, Houston Ctr Excellence Hlth Serv Res, Houston, TX USA. [Wilson, N. L.; Kunik, M. E.] Baylor Coll Med, Houston, TX 77030 USA. [Bass, D. M.; Looman, W. J.] Benjamin Rose Res Inst, Cleveland, OH USA. [Judge, K.] Cleveland State Univ, Dept Psychol, Cleveland, OH 44115 USA. [Moye, J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 447 EP 447 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602003028 ER PT J AU Mulligan, EA Schuster, J Naik, AD Gosian, J Doherty, KM Moye, J AF Mulligan, E. A. Schuster, J. Naik, A. D. Gosian, J. Doherty, K. M. Moye, J. TI DO MILITARY VETERANS IDENTIFY CANCER AS A TRAUMATIC STRESSOR? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mulligan, E. A.; Schuster, J.; Gosian, J.; Doherty, K. M.; Moye, J.] VA Boston Healthcare Syst, Boston, MA USA. [Mulligan, E. A.; Moye, J.] Harvard Univ, Sch Med, Boston, MA USA. [Mulligan, E. A.] Washington Univ, St Louis, MO USA. [Schuster, J.] Natl Ctr PTSD Womens Hlth Sci Div, Boston, MA USA. [Naik, A. D.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Naik, A. D.] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 458 EP 459 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602003076 ER PT J AU Karel, MJ Moye, J Norris, R Archambault, E Walder, A Naik, A AF Karel, M. J. Moye, J. Norris, R. Archambault, E. Walder, A. Naik, A. TI ADULT DEVELOPMENTAL PERSPECTIVES ON COPING WITH CANCER: LIFE ACTIVITIES, SATISFACTION, AND DEPRESSION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Karel, M. J.; Moye, J.; Norris, R.; Archambault, E.] VA Boston Healthcare Syst, Mental Hlth, Brockton, MA USA. [Walder, A.; Naik, A.] Michael E DeBakey VAMC, Houston, TX USA. [Karel, M. J.; Moye, J.] Harvard Univ, Sch Med, Boston, MA USA. [Naik, A.] Baylor Med Sch, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 459 EP 460 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602003080 ER PT J AU Mulligan, EA AF Mulligan, E. A. TI MEASURING PREDEATH GRIEF IN FAMILY CAREGIVERS OF PERSONS WITH DEMENTIA SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mulligan, E. A.] Washington Univ, St Louis, MO USA. [Mulligan, E. A.] VA Boston Healthcare Syst, Boston, MA USA. [Mulligan, E. A.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 461 EP 461 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602003088 ER PT J AU Kostas, TR Hurwitz, S Bernacki, R AF Kostas, T. R. Hurwitz, S. Bernacki, R. TI A MULTIPRONGED APPROACH TO IMPROVING GERIATRIC COMPETENCY IN INTERNAL MEDICINE RESIDENTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kostas, T. R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Hurwitz, S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hurwitz, S.] Harvard Univ, Sch Med, Boston, MA USA. [Bernacki, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bernacki, R.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 469 EP 469 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602003123 ER PT J AU Wang, J Kaiser, AP Seligowski, AV Potter, C Spiro, A King, L King, D Brady, CB AF Wang, J. Kaiser, A. Pless Seligowski, A. V. Potter, C. Spiro, A. King, L. King, D. Brady, C. B. TI LATE-ONSET STRESS SYMPTOMATOLOGY: DEVELOPMENT AND VALIDATION OF A SHORT-FORM SCREENING INSTRUMENT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Wang, J.; Kaiser, A. Pless; Seligowski, A. V.; Potter, C.; Spiro, A.; King, L.; King, D.; Brady, C. B.] VA Boston Healthcare Syst, Boston, MA USA. [Kaiser, A. Pless; Spiro, A.; King, L.; King, D.; Brady, C. B.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Spiro, A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 475 EP 475 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602003146 ER PT J AU Cotter, VT Streim, JE O'Donnell, DF Forciea, M Evans, LK AF Cotter, V. T. Streim, J. E. O'Donnell, D. F. Forciea, M. Evans, L. K. TI TRAINING INITIATIVES IN BEHAVIORAL TREATMENT PLANNING IN LONG-TERM CARE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Cotter, V. T.; Evans, L. K.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Streim, J. E.; Forciea, M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Streim, J. E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [O'Donnell, D. F.] Coatesville VA Med Ctr, Coatesville, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 479 EP 479 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602003163 ER PT J AU Byers, AL Vittinghoff, E Lui, L Covinsky, K Cauley, JA Ensrud, K Hillier, TA Yaffe, K AF Byers, A. L. Vittinghoff, E. Lui, L. Covinsky, K. Cauley, J. A. Ensrud, K. Hillier, T. A. Yaffe, K. TI CHARACTERIZATION OF LONG-TERM DEPRESSIVE TRAJECTORIES AMONG ELDERLY WOMEN SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Byers, A. L.; Vittinghoff, E.; Covinsky, K.; Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Byers, A. L.; Covinsky, K.; Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Lui, L.] Calif Pacific Med Ctr Res Inst, San Francisco, CA USA. [Cauley, J. A.] Univ Pittsburgh, Pittsburgh, PA USA. [Ensrud, K.] Univ Minnesota, Minneapolis, MN USA. [Ensrud, K.] Minneapolis VA Med Ctr, Minneapolis, MN USA. [Hillier, T. A.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 518 EP 518 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602003331 ER PT J AU Turiano, NA Hill, PL Roberts, BW Spiro, A Mroczek, D AF Turiano, N. A. Hill, P. L. Roberts, B. W. Spiro, A. Mroczek, D. TI SMOKING MEDIATES THE ASSOCIATION BETWEEN CONSCIENTIOUSNESS AND MORTALITY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Turiano, N. A.; Mroczek, D.] Purdue Univ, W Lafayette, IN 47907 USA. [Turiano, N. A.; Mroczek, D.] Ctr Aging & Life Course, W Lafayette, IN USA. [Hill, P. L.; Roberts, B. W.] Univ Illinois, Champaign, IL USA. [Spiro, A.] VA Boston Healthcare Syst, Boston, MA USA. [Spiro, A.] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 519 EP 520 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602003341 ER PT J AU Hung, WW Morano, B Boockvar, K AF Hung, W. W. Morano, B. Boockvar, K. TI FEASIBILITY OF INTEGRATING THE USE OF REGIONAL HEALTH INFORMATION ORGANIZATION FOR A VA-BASED CARE TRANSITION INTERVENTION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hung, W. W.; Morano, B.; Boockvar, K.] James J Peters Vet Affairs Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, Bronx, NY USA. [Hung, W. W.; Morano, B.; Boockvar, K.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Hung, W. W.; Morano, B.; Boockvar, K.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 526 EP 526 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602003374 ER PT J AU Goldstein, RH Miller, EA AF Goldstein, R. H. Miller, E. A. TI THE ROLE OF THE MEDIA IN LONG-TERM CARE REBALANCING: A COMPARATIVE STATE ANALYSIS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Goldstein, R. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Miller, E. A.] Univ Massachusetts, McCormack Grad Sch Policy & Global Studies, Boston, MA 02125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 548 EP 548 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602003489 ER PT J AU Paquin, AM Rudolph, JL Quinlan, N Salow, M AF Paquin, A. M. Rudolph, J. L. Quinlan, N. Salow, M. TI PILL CLINIC: A POST-DISCHARGE MEDICATION SERVICE FOR OLDER VETERANS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Paquin, A. M.; Rudolph, J. L.; Quinlan, N.; Salow, M.] VA Boston Healthcare Syst, GRECC, Boston, MA USA. [Paquin, A. M.; Salow, M.] VA Boston Healthcare Syst, Dept Pharm, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 557 EP 557 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602003533 ER PT J AU Archambault, E Hill, J Lawrence, K Kelly, B Rudolph, JL AF Archambault, E. Hill, J. Lawrence, K. Kelly, B. Rudolph, J. L. TI COMING HOME FROM THE HOSPITAL: SUPPORT FOR VETERANS WITH COGNITIVE IMPAIRMENT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Archambault, E.; Hill, J.; Lawrence, K.; Kelly, B.; Rudolph, J. L.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 558 EP 558 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602003535 ER PT J AU Schulman-Green, DJ Fennie, K McCorkle, R Bradley, E Prigerson, H Knobf, T DiGiovanna, M Dixon, J AF Schulman-Green, D. J. Fennie, K. McCorkle, R. Bradley, E. Prigerson, H. Knobf, T. DiGiovanna, M. Dixon, J. TI VALIDATION OF AN INSTRUMENT TO MEASURE UNDERSTANDING OF CURATIVE, PALLIATIVE AND HOSPICE CARE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Schulman-Green, D. J.; Fennie, K.; McCorkle, R.; Knobf, T.; Dixon, J.] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. [Prigerson, H.] Harvard Univ, Cambridge, MA 02138 USA. [Prigerson, H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [DiGiovanna, M.] Yale Univ, Sch Med, New Haven, CT USA. [McCorkle, R.; Bradley, E.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 571 EP 571 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602004003 ER PT J AU Mlinac, M Stamm, K Lees, F Saint, J Mulligan, J AF Mlinac, M. Stamm, K. Lees, F. Saint, J. Mulligan, J. TI LONGITUDINAL PATTERNS OF GOAL MAINTENANCE AND RESILIENCE IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mlinac, M.] VA Boston Healthcare Syst, Boston, MA USA. [Mlinac, M.] Harvard Univ, Sch Med, Boston, MA USA. [Stamm, K.; Lees, F.; Saint, J.; Mulligan, J.] Univ Rhode Isl, Kingston, RI 02881 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 579 EP 579 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602004042 ER PT J AU Vuckovic, NH Edes, T Nichols, LO AF Vuckovic, N. H. Edes, T. Nichols, L. O. TI I COULDN'T MAKE IT WITHOUT THEM: PATIENT AND CAREGIVER PERSPECTIVE OF HOME BASED PRIMARY CARE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Vuckovic, N. H.] Intel Corp, Hlth Res & Innovat, Beaverton, OR USA. [Edes, T.] US Dept Vet Affairs, Washington, DC USA. [Nichols, L. O.] Vet Affairs Med Ctr, Memphis, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 614 EP 614 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602004207 ER PT J AU Stephens, C Covinsky, K Blegen, MA Lee, S AF Stephens, C. Covinsky, K. Blegen, M. A. Lee, S. TI FALLS ARE A POWERFUL DETERMINANT OF ER USE BY NURSING HOME RESIDENTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Stephens, C.; Covinsky, K.; Blegen, M. A.; Lee, S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Stephens, C.; Covinsky, K.; Lee, S.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2011 VL 51 SU 2 BP 627 EP 627 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 936PH UT WOS:000303602004268 ER PT J AU Gupta, P Goyal, S Tobias, JD Prodhan, P Purohit, P Gossett, JM Chow, V Noviski, N AF Gupta, Punkaj Goyal, Sunali Tobias, Joseph D. Prodhan, Parthak Purohit, Prashant Gossett, Jeffrey M. Chow, Vinca Noviski, Natan TI Risk factors associated with hospital admission among healthy children with adenovirus infection SO TURKISH JOURNAL OF PEDIATRICS LA English DT Article DE adenovirus; hospital admission; respiratory distress; wheezing; acute gastroenteritis ID RESPIRATORY SYNCYTIAL VIRUS; BRONCHIOLITIS OBLITERANS; CLINICAL-FEATURES; YOUNG-CHILDREN; TRACT INFECTION; INFANTS; EPIDEMIOLOGY; PNEUMONIA AB Gupta P, Goyal S, Tobias JD, Prodhan P, Purohit P, Gossett JM, Chow V, Noviski N. Risk factors associated with hospital admission among healthy children with adenovirus infection. Turk J Pediatr 2011; 53: 597-603. Adenovirus infections mimic bacterial infections on initial presentation in healthy children, leading to higher likelihood of hospital admission. The objective of this study was to identify risk factors associated with hospital admission in previously healthy children with adenovirus infection. This is a retrospective study of 125 previously healthy children, who tested positive with direct immunofluorescence assay (DFA) for adenoviral infection at our center between January 2001 and October 2007. The primary outcome of the study was the need for hospital admission. The relationship between clinical variables at initial emergency room (ER) presentation and need for hospital admission were explored using univariate and multivariate logistic regression models. The model's predictive value was investigated by calculating the area under the receiver operating characteristic (ROC) curve and Hosmer-Lemeshow test. On stepwise multivariate logistic regression analysis, the presence of respiratory distress (odds ratio [OR]: 5.6; p=0.014), acute gastroenteritis (OR: 3.8; p=0.019) and wheezes at initial presentation (OR: 6.5; p=0.003) at the time of initial presentation in the ER were associated with need for hospital admission. For this model, the area under the ROC curve was 0.79, and there was no evidence of lack of fit on Hosmer-Lemeshow goodness-of-fit test (p=0.56). Our study identifies three risk factors, namely, respiratory distress, wheezing and acute gastroenteritis, associated with hospital admission for healthy children with adenoviral infections. C1 [Gupta, Punkaj; Prodhan, Parthak] Univ Arkansas Med Ctr, Sect Pediat Cardiol & Crit Care, Little Rock, AR USA. [Gossett, Jeffrey M.] Univ Arkansas Med Ctr, Biostat Program, Dept Pediat, Little Rock, AR USA. [Goyal, Sunali] Univ Arkansas Med Ctr, Dept Ophthalmol, Little Rock, AR USA. [Gupta, Punkaj; Purohit, Prashant; Noviski, Natan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Crit Care, Boston, MA USA. [Tobias, Joseph D.] Nationwide Childrens Hosp, Dept Anesthesiol, Columbus, OH USA. [Tobias, Joseph D.] Nationwide Childrens Hosp, Dept Pediat, Columbus, OH USA. [Tobias, Joseph D.] Ohio State Univ, Columbus, OH 43210 USA. [Chow, Vinca] Stanford Univ Med Ctr, Dept Med Educ, Palo Alto, CA USA. RP Gupta, P (reprint author), Univ Arkansas Med Ctr, Sect Pediat Cardiol & Crit Care, Little Rock, AR USA. NR 27 TC 2 Z9 2 U1 0 U2 1 PU TURKISH J PEDIATRICS PI ANKARA PA P K 66 SAMANPAZARI, 06240 ANKARA, TURKEY SN 0041-4301 J9 TURKISH J PEDIATR JI Turk. J. Pediatr. PD NOV-DEC PY 2011 VL 53 IS 6 BP 597 EP 603 PG 7 WC Pediatrics SC Pediatrics GA 911BA UT WOS:000301691100001 PM 22389981 ER PT J AU Jue, JJS Metlay, JP AF Jue, J. Jane S. Metlay, Joshua P. TI Web-Based Health Resources at US Colleges: Early Patterns and Missed Opportunities in Preventive Health SO PREVENTING CHRONIC DISEASE LA English DT Article ID STUDENT POPULATION; CONTROLLED-TRIAL; UNITED-STATES; INTERNET USE; INFORMATION; ADOLESCENTS; INTERVENTIONS; TECHNOLOGY; PREVALENCE; BEHAVIOR AB Introduction Web-based health resources on college websites have the potential to reach a substantial number of college students. The objective of this study was to characterize how colleges use their websites to educate about and promote health. Methods This study was a cross-sectional analysis of websites from a nationally representative sample of 426 US colleges. Reviewers abstracted information about Web-based health resources from college websites, namely health information, Web links to outside health resources, and interactive Web-based health programs. Results Nearly 60% of US colleges provided health resources on their websites, 49% provided health information, 48% provided links to outside resources, and 28% provided interactive Web-based health programs. The most common topics of Web-based health resources were mental health and general health. Conclusion We found widespread presence of Web-based health resources available from various delivery modes and covering a range of health topics. Although further research in this new modality is warranted, Web-based health resources hold promise for reaching more US college students. C1 [Jue, J. Jane S.] Philadelphia VA Med Ctr, Dept Vet Affairs, Philadelphia, PA USA. [Jue, J. Jane S.] Univ Penn, Sch Med, Robert Wood Johnson Fdn Clin Scholars Program, Philadelphia, PA 19104 USA. RP Jue, JJS (reprint author), ECRI Inst, 5200 Butler Pike, Plymouth Meeting, PA 19462 USA. EM janejuemd@gmail.com FU Robert Wood Johnson Foundation at the University of Pennsylvania; Department of Veterans Affairs; University of Pennsylvania [K24-AI073957] FX During the course of this study, Dr Jue was funded by the Robert Wood Johnson Foundation Clinical Scholars Program at the University of Pennsylvania in partnership with the Department of Veterans Affairs. Dr Metlay was funded by a Mid-Career Patient Oriented Investigator Award (K24-AI073957) at the University of Pennsylvania. Neither funding entities had a role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; nor preparation, review, or approval of the manuscript. NR 30 TC 1 Z9 1 U1 2 U2 5 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD NOV PY 2011 VL 8 IS 6 AR A138 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 896JZ UT WOS:000300563000021 PM 22005631 ER PT J AU Peacock, JM Keo, HH Duval, S Baumgartner, I Oldenburg, NC Jaff, MR Henry, TD Yu, XH Hirsch, AT AF Peacock, James M. Keo, Hong H. Duval, Sue Baumgartner, Iris Oldenburg, Niki C. Jaff, Michael R. Henry, Timothy D. Yu, Xinhua Hirsch, Alan T. TI The Incidence and Health Economic Burden of Ischemic Amputation in Minnesota, 2005-2008 SO PREVENTING CHRONIC DISEASE LA English DT Article ID LOWER-EXTREMITY; VASCULAR-DISEASE; BYPASS-SURGERY; UNITED-STATES; MANAGEMENT; ANGIOPLASTY; DISPARITIES; PREVALENCE; CARE AB Introduction Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease (PAD), is associated with high rates of myocardial infarction, stroke, and amputation, and has a high health economic cost. The objective of this study was to estimate the incidence of lower limb amputation, the most serious consequence of CLI, and to create a surveillance methodology for the incidence of ischemic amputation in Minnesota. Methods We assessed the incidence of ischemic amputation using all inpatient hospital discharge claims in Minnesota from 2005 through 2008. We identified major and minor ischemic amputations via the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) procedure codes for lower limb amputation not due to trauma or cancer and assessed geographic and demographic differences in the incidence of ischemic amputation. Results The age-adjusted annual incidence of lower limb ischemic amputation in Minnesota during the 4-year period was 20.0 per 100,000 (95% confidence interval, 19.4-20.6). Amputations increased significantly with age, were more common in men and in people with diabetes, and were slightly more common in rural residents. The number of amputation-related hospitalizations was steady over 4 years. The median total charge for each amputation was $32,129, and cumulative inpatient hospitalization charges were $56.5 million in 2008. Conclusion The incidence of ischemic amputation is high and results in major illness and health economic costs. These data represent the first population-based estimate of ischemic amputation at the state level and provide a national model for state-based surveillance. C1 [Keo, Hong H.; Duval, Sue; Oldenburg, Niki C.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Keo, Hong H.; Duval, Sue; Henry, Timothy D.] Minneapolis Heart Inst Fdn, Minneapolis, MN USA. [Keo, Hong H.; Baumgartner, Iris] Univ Hosp Bern, Div Angiol, Swiss Cardiovasc Ctr, CH-3010 Bern, Switzerland. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jaff, Michael R.] Harvard Univ, Sch Med, Boston, MA USA. [Yu, Xinhua] Univ Memphis, Sch Publ Hlth, Dept Epidemiol & Biostat, Memphis, TN 38152 USA. [Hirsch, Alan T.] Univ Minnesota, Sch Med, Cardiovasc Div, Minneapolis, MN 55455 USA. [Hirsch, Alan T.] Univ Minnesota, Sch Med, Lillihei Heart Inst, Minneapolis, MN 55455 USA. RP Peacock, JM (reprint author), Minnesota Dept Hlth, Ctr Hlth Promot, Hlth Promot & Chron Dis Div, POB 64882, St Paul, MN 55164 USA. EM james.peacock@state.mn.us FU Centers for Disease Control and Prevention [5U50DP000721-04] FX This work was funded by grant no. 5U50DP000721-04 from the Centers for Disease Control and Prevention. NR 28 TC 16 Z9 16 U1 0 U2 3 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD NOV PY 2011 VL 8 IS 6 AR A141 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 896JZ UT WOS:000300563000024 PM 22005634 ER PT J AU Hamburger, M Baraf, HSB Adamson, TC Basile, J Bass, L Cole, B Doghramji, PP Guadagnoli, GA Hamburger, F Harford, R Lieberman, JA Mandel, DR Mandelbrot, DA McClain, BP Mizuno, E Morton, AH Mount, DB Pope, RS Rosenthal, KG Setoodeh, K Skosey, JL Edwards, NL AF Hamburger, Max Baraf, Herbert S. B. Adamson, Thomas C., III Basile, Jan Bass, Lewis Cole, Brent Doghramji, Paul P. Guadagnoli, Germano A. Hamburger, Frances Harford, Regine Lieberman, Joseph A., III Mandel, David R. Mandelbrot, Didier A. McClain, Bonny P. Mizuno, Eric Morton, Allan H. Mount, David B. Pope, Richard S. Rosenthal, Kenneth G. Setoodeh, Katy Skosey, John L. Edwards, N. Lawrence TI 2011 Recommendations for the Diagnosis and Management of Gout and Hyperuricemia SO PHYSICIAN AND SPORTSMEDICINE LA English DT Article DE gout; hyperuricemia; guideline recommendations; rheumatology ID SERUM URIC-ACID; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INDEPENDENT RISK-FACTOR; POPULATION-BASED COHORT; URATE-LOWERING THERAPY; TREATMENT-FAILURE GOUT; CHRONIC-RENAL-FAILURE; METABOLIC SYNDROME; DOUBLE-BLIND; LONG-TERM AB Gout is a major health problem in the United States; it affects 8.3 million people, which is approximately 4% of the adult population. Gout is most often diagnosed and managed in primary care practices; thus, primary care physicians have a significant opportunity to improve patient outcomes. Following publication of the 2006 European League Against Rheumatism (EULAR) gout guidelines, significant new evidence has accumulated, and new treatments for patients with gout have become available. It is the objective of these 2011 recommendations to update the 2006 EULAR guidelines, paying special attention to the needs of primary care physicians. The revised 2011 recommendations are based on the Grading of Recommendations Assessment, Development, and Evaluation approach as an evidence-based strategy for rating quality of evidence and grading the strength of recommendation formulated for use in clinical practice. A total of 26 key recommendations, 10 for diagnosis and 16 for management, of patients with gout were evaluated, resulting in important updates for patient care. The presence of monosodium urate crystals and/or tophus and response to colchicine have the highest clinical diagnostic value. The key aspect of effective management of an acute gout attack is initiation of treatment within hours of symptom onset. Low-dose colchicine is better tolerated and is as effective as a high dose. When urate-lowering therapy (ULT) is indicated, the xanthine oxidase inhibitors allopurinol and febuxostat are the options of choice. Febuxostat can be prescribed at unchanged doses for patients with mild-to-moderate renal or hepatic impairment. The target of ULT should be a serum uric acid level that is 6 mg/dL. For patients with refractory and tophaceous gout, intravenous pegloticase is a new treatment option. This article is a summary of the 2011 clinical guidelines published in Postgraduate Medicine. This article provides a streamlined, accessible overview intended for quick review by primary care physicians, with the full guidelines being a resource for those seeking additional background information and expanded discussion. C1 [Hamburger, Max] Rheumatol Associates Long Isl, Melville, NY 11747 USA. [Hamburger, Max] SUNY Stony Brook, Stony Brook, NY USA. [Hamburger, Max] Amer Soc Clin Rheumatologists, Melville, NY USA. [Baraf, Herbert S. B.] George Washington Univ, Wheaton, IL USA. [Adamson, Thomas C., III] Sharp Rees Stealy Med Grp, Div Rheumatol, San Diego, CA USA. [Basile, Jan] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Seinsheimer Cardiovasc Hlth Program, Div Gen Internal Med, Charleston, SC 29425 USA. [Bass, Lewis] NYCOM, Ridgewood, NY USA. [Bass, Lewis] Touro Coll Osteopath Med TouroCOM, Ridgewood, NY USA. [Doghramji, Paul P.] Ursinus Coll, Collegeville, PA USA. [Guadagnoli, Germano A.] Bridgeport Hosp, Rheumatol Sect, Bridgeport, CT USA. [Hamburger, Frances] Rheumatol Associates Long Isl, Psychol Serv, Dix Hills, NY USA. [Lieberman, Joseph A., III] Jefferson Med Coll, Hockessin, DE USA. [Mandelbrot, Didier A.; Mount, David B.] Harvard Univ, Sch Med, Boston, MA USA. [McClain, Bonny P.] ASSESSmint Analyt & Outcomes, Greensboro, NC USA. [Mizuno, Eric] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Morton, Allan H.] Michigan State Univ, Coll Osteopath Med, E Lansing, MI 48824 USA. [Mount, David B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Pope, Richard S.] Quinnipiac Univ, Dept PA Studies, Hamden, CT USA. [Skosey, John L.] Univ Chicago, Chicago, IL 60637 USA. [Edwards, N. Lawrence] Univ Florida, Dept Med, Gainesville, FL USA. RP Hamburger, M (reprint author), Rheumatol Associates Long Isl, 1895 Walt Whitman Rd, Melville, NY 11747 USA. EM mcapacious@aol.com FU Regine Harford; MS; MSTPC; URL Pharma; American Society of Clinical Rheumatologists; Mary Shah; MLS; medical library archivist and Caroline Marshall; Danbury Hospital Library; Abbott; Amgen; Bristol-Myers Squibb; Crescendo Bioscience; Genentech; Janssen Biotech; Takeda Pharmaceuticals; North America, Inc; NHLBI (SPRINT); AstraZeneca; Biogen Idec; Celegene; Merck Sharp and Dohme; Novartis; Pfizer; Roche; Stryker; VQ OrthoCare; Nuon Therapeutics FX The authors wish to gratefully acknowledge the invaluable editorial support from Regine Harford, MS, MSTPC, and statistical support from Bonny McClain, MS, DC of ASSESS-mint Analytics. Funding for the preparation of the article was received from URL Pharma, and from the American Society of Clinical Rheumatologists. The authors also wish to acknowledge the invaluable support from Mary Shah, MLS, medical library archivist and Caroline Marshall, MLS, health sciences librarian, both from Danbury Hospital Library.; Max Hamburger, MD is a member of the speakers' bureau for Abbott, Amgen, Bristol-Myers Squibb, Genentech, GSK, HGSI, Novartis, and UCB; is a consultant for Bristol-Myers Squibb, Genentech, and UCB; is in receipt of educational grants in support of CME activities from Abbott, Amgen, Bristol-Myers Squibb, Crescendo Bioscience, Genentech, Janssen Biotech, Takeda Pharmaceuticals, North America, Inc, and URL Pharma. Herbert S. B. Baraf, MD is a member of the speakers' bureau for Savient Pharmaceuticals and Takeda Pharmaceuticals, North America, Inc; is a consultant for Ardea Biosciences and Savient Pharmaceuticals; is an investigator for Ardea Biosciences, Metabolex, Novartis, Regeneron, Savient Pharmaceuticals., and Takeda Pharmaceuticals, North America, Inc; and is a member of the advisory board for Takeda Pharmaceuticals, North America, Inc. Thomas C. Adamson III, MD, FACP, CPE is a member of the speakers' bureau for sanofi-aventis, Takeda Pharmaceuticals, North America, Inc, and Warner Chilcott; and is a consultant for Sanofi-Aventis and Takeda Pharmaceuticals, North America, Inc. Jan Basile, MD is a member of the speakers' bureau for Boehringer Ingelheim, Daiichi-Sankyo, Forest Laboratories, and Takeda Pharmaceuticals, North America, Inc; is a consultant for Daiichi-Sankyo, Eli Lilly/Boehringer Ingelheim, Forest Laboratories, and Takeda Pharmaceuticals, North America, Inc; and has received grant/research support from the NHLBI (SPRINT). Lewis Bass, DO, FACOFP discloses no conflicts of interest. Brent Cole, MD discloses no conflicts of interest. Paul P. Doghramji, MD is a member of the speakers' bureau and advisory board for URL Pharma. Germano A. Guadagnoli, MD is a member of the speakers' bureau for Amgen/Pfizer, Forest Laboratories, and Takeda Pharmaceuticals, North America, Inc. Frances Hamburger, PhD is employed by Miller Professional Group. Regine Harford, MS, MSTPC discloses no conflicts of interest. Joseph A. Lieberman III, MD, MPH is a member of the advisory board for Takeda Pharmaceuticals, North America, Inc and URL Pharma. David R. Mandel, MD is a member of the speakers' bureau for Abbott, Amgen, Auxilium Pharmaceuticals, Forest Laboratories, Forest Pharmaceuticals, GlaxoSmithKline, Lilly, Novartis, Savient Pharmaceuticals, Sunovion Pharmaceuticals, Takeda Pharmaceuticals, North America, Inc, and UCB; is a member of the advisory board for Amgen, Auxilium Pharmaceuticals, Crescendo Bioscience, Pfizer, and Savient Pharmaceuticals; is a consultant for Amgen, Auxilium Pharmaceuticals; Crescendo Bioscience, Pfizer, Savient Pharmaceuticals, and UCB; and has received research support from Abbott, Amgen, AstraZeneca, Biogen Idec, Celegene, Janssen Biotech, Crescendo Bioscience, Genentech, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Stryker, and VQ OrthoCare. Didier A. Mandelbrot, MD discloses no conflicts of interest. Bonny P. McClain, MS, DC discloses no conflicts of interest. Eric Mizuno, MD is an advisor for Takeda Pharmaceuticals, North America, Inc. Allan H. Morton, DO is a member of the speakers' bureau for Abbott, Amgen, Bristol-Myers Squibb, Genentech, Pfizer, Takeda Pharmaceuticals, North America, Inc, Savient Pharmaceuticals, UCB, URL Pharma, and Warner Chilcott; and is a consultant for Amgen, Bristol-Myers Squibb, Novartis, Pfizer, Savient Pharmaceuticals, UCB, and URL Pharma. David B.; Mount, MD has received grant support from Nuon Therapeutics; is on the medical advisory board and educational planning committees for Savient Pharmaceuticals; and provides internal talks for Takeda Pharmaceuticals, North America, Inc; nd has pending grants with Takeda Pharmaceuticals, North America, Inc and URL Pharma. Richard S. Pope, MPAS, PA-C, DFAAPA is a member of the speakers' bureau for AstraZeneca, Amgen, Takeda Pharmaceuticals, North America, Inc, UCB, and URL Pharma. Kenneth G. Rosenthal, MD, PC discloses no conflicts of interest. Katy Setoodeh, MD, FACR is a member of the speakers' bureau for Amgen and Human Genome Sciences. John L. Skosey, MD, PhD, FACR, FACP is an advisory board participant for Cardinal Health; a director of Theratest Laboratories; and a stockholder in Amgen. N. Lawrence Edwards, MD, FACP, FACR is a consultant for Ardea Biosciences, Savient Pharmaceuticals, Novartis, and Takeda Pharmaceuticals, North America, Inc. NR 137 TC 20 Z9 26 U1 4 U2 20 PU JTE MULTIMEDIA PI BERWYN PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA SN 0091-3847 J9 PHYSICIAN SPORTSMED JI Physician Sportsmed. PD NOV PY 2011 VL 39 IS 4 BP 98 EP 123 DI 10.3810/psm.2011.11.1946 PG 26 WC Primary Health Care; Orthopedics; Sport Sciences SC General & Internal Medicine; Orthopedics; Sport Sciences GA 893VD UT WOS:000300384200016 PM 22293773 ER PT J AU Brooks-Worrell, B Tree, T Mannering, SI Durinovic-Bello, I James, E Gottlieb, P Wong, S Zhou, Z Yang, L Cilio, CM Reichow, J Menart, B Rutter, R Schreiner, R Pham, M de Marquesini, LP Lou, O Scotto, M Mallone, R Schloot, NC AF Brooks-Worrell, B. Tree, T. Mannering, S. I. Durinovic-Bello, I. James, E. Gottlieb, P. Wong, S. Zhou, Z. Yang, L. Cilio, C. M. Reichow, J. Menart, B. Rutter, R. Schreiner, R. Pham, M. de Marquesini, L. Petrich Lou, O. Scotto, M. Mallone, R. Schloot, N. C. CA Immunology Diabet Soc TI Comparison of cryopreservation methods on T-cell responses to islet and control antigens from type 1 diabetic patients and controls SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article; Proceedings Paper CT 11th International Congress of the Immunology-of-Diabetes-Society (IDS) CY OCT 31-NOV 03, 2010 CL Incheon, SOUTH KOREA SP Immunol Diabet Soc (IDS) DE T cells; proliferation; ELISPOT; tetramer; cryopreservation; CFSE; islet antigens; type 1 diabetes ID BLOOD MONONUCLEAR-CELLS; PROINSULIN; IMMUNOLOGY; PHENOTYPE; PROTEINS; WORKSHOP; SUBSETS; SOCIETY; LYT-2+; L3T4+ AB Background Type 1 diabetes (T1D) is a cell-mediated autoimmune disease characterized by destruction of the pancreatic islet cells. The use of cryopreserved cells is preferable to the use of freshly isolated cells to monitor clinical trials to decrease assay and laboratory variability. Methods The T-Cell Workshop Committee of the Immunology of Diabetes Society compared two widely accepted T-cell freezing protocols (warm and cold) to freshly isolated peripheral blood mononuclear cells from patients with T1D and controls in terms of recovery, viability, cell subset composition, and performance in functional assays currently in use in T1D-related research. Nine laboratories participated in the study with four different functional assays included. Results The cold freezing method yielded higher recovery and viability compared with the warm freezing method. Irrespective of freezing protocol, B cells and CD8+ T cells were enriched, monocyte fraction decreased, and islet antigen-reactive responses were lower in frozen versus fresh cells. However, these results need to take in to account that the overall response to islet autoantigens was low in some assays. Conclusions In the current study, none of the tested T-cell functional assays performed well using frozen samples. More research is required to identify a freezing method and a T-cell functional assay that will produce responses in patients with T1D comparable to responses using fresh peripheral blood mononuclear cells. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Brooks-Worrell, B.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Tree, T.] Kings Coll London, Sch Med, London WC2R 2LS, England. [Mannering, S. I.] Univ Melbourne, Dept Med, St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. [Durinovic-Bello, I.; James, E.] Benaroya Res Inst, Seattle, WA USA. [Gottlieb, P.] Univ Colorado, Sch Med, Barbara Davis Ctr Childhood Diabet, Dept Pediat & Med, Denver, CO USA. [Wong, S.] Cardiff Univ, Ctr Endocrine & Diabet Sci, Dept Med, Sch Med, Cardiff, S Glam, Wales. [Zhou, Z.; Yang, L.] Cent S Univ, Sch Med, Changsha, Hunan, Peoples R China. [Cilio, C. M.] Lund Univ, Dept Sci, Cellular Autoimmun Unit, Malmo, Sweden. [Reichow, J.] Seattle Inst Biomed & Clin Res, Seattle, WA USA. [Menart, B.; Rutter, R.; Schreiner, R.; Pham, M.; Schloot, N. C.] Univ Dusseldorf, German Diabet Ctr, Inst Clin Diabetol, D-40225 Dusseldorf, Germany. [de Marquesini, L. Petrich] Univ Bristol, Henry Wellcome Lab Integrat Neurosci & Endocrinol, Bristol, Avon, England. [Lou, O.] JDRF Int, JDRF Canadian Clin Trial Network, Toronto, ON, Canada. [Scotto, M.; Mallone, R.] Hop St Vincent de Paul, INSERM, U986, DeAR Lab Avenir, F-75674 Paris, France. [Schloot, N. C.] Univ Dusseldorf, Clin Metab Dis, D-40225 Dusseldorf, Germany. RP Brooks-Worrell, B (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM bbrooks@u.washington.edu RI Mallone, Roberto/H-4430-2013; OI James, Eddie/0000-0002-7217-5729 NR 25 TC 9 Z9 9 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD NOV PY 2011 VL 27 IS 8 SI SI BP 737 EP 745 DI 10.1002/dmrr.1245 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 889XD UT WOS:000300108000004 PM 22069253 ER PT J AU Medarova, Z Greiner, DL Ifediba, M Dai, GP Bolotin, E Castillo, G Bogdanov, A Kumar, M Moore, A AF Medarova, Zdravka Greiner, Dale L. Ifediba, Marytheresa Dai, Guangping Bolotin, Elijah Castillo, Gerardo Bogdanov, Alexei Kumar, Mohanraja Moore, Anna TI Imaging the pancreatic vasculature in diabetes models SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article; Proceedings Paper CT 11th International Congress of the Immunology-of-Diabetes-Society (IDS) CY OCT 31-NOV 03, 2010 CL Incheon, SOUTH KOREA SP Immunol Diabet Soc (IDS) DE imaging; inflammation; vasculature; diabetes; protected graft copolymer ID MAGNETIC-RESONANCE MICROSCOPY; ISLET BLOOD PERFUSION; PERMEABILITY; FLOW; RAT; MOUSE; STREPTOZOTOCIN; VOLUME; PHASE; GRAFT AB Background Vascular parameters, such as vascular volume, flow, and permeability, are important disease biomarkers for both type 1 and type 2 diabetes. Therefore, it is essential to develop approaches to monitor the changes in pancreatic microvasculature non-invasively. Methods Here, we describe the application of the long-circulating, paramagnetic T1 contrast agent, protected Graft Copolymer bearing covalently linked gadolinium diethylenetriaminepentaacetic acid residues and labelled with fluorescein (PGC-GdDTPA-F) for the non-invasive semi-quantitative evaluation of vascular changes in diabetic models using magnetic resonance imaging. Results We observed a significantly higher accumulation of protected graft copolymer bearing covalently linked gadolinium diethylenetriaminepentaacetic acid residues and labelled with fluorescein in the pancreata of BBDR rats induced to develop diabetes, as compared to non-diabetic controls at 1 h post-injection. No differences were seen in the blood pool, kidney, or muscle, indicating that the effect is specific to the diabetic pancreas. Fluorescence microscopy revealed a marked increase in contrast agent availability in the pancreas with the development of the pathology. Similar changes were noted in the homozygous Lepr(db) mouse model of type 2 diabetes. This effect appeared to result both from the increase of vascular volume and permeability. Conclusions High-molecular weight paramagnetic blood volume contrast agents are valuable for the in vivo definition of pancreatic microvasculature dynamics by magnetic resonance imaging. The increase in vascular volume and permeability, associated with diabetic inflammation, can be monitored non-invasively and semi-quantitatively by magnetic resonance imaging in diabetic BBDR rats. This imaging strategy represents a valuable research tool for better understanding of the pathologic process. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Medarova, Zdravka; Ifediba, Marytheresa; Dai, Guangping; Kumar, Mohanraja; Moore, Anna] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Mol Imaging Lab,Athinoula A Martinos Ctr Biomed I, Charlestown, MA 02129 USA. [Greiner, Dale L.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA USA. [Bolotin, Elijah; Castillo, Gerardo] PharmaIN Corp, Seattle, WA USA. [Bogdanov, Alexei] Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA USA. [Bogdanov, Alexei] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA. RP Moore, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Mol Imaging Lab,Athinoula A Martinos Ctr Biomed I, Bldg 75,13th St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu FU NIDDK NIH HHS [R44 DK069727, DK080264, P30 DK032520, R43 DK069727, R24 DK080264, DK069727, U01 DK089572, DK32520, DK089572] NR 26 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD NOV PY 2011 VL 27 IS 8 SI SI BP 767 EP 772 DI 10.1002/dmrr.1249 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 889XD UT WOS:000300108000008 PM 22069257 ER PT J AU Klupa, T Solecka, I Nowak, N Szopa, M Kiec-Wilk, B Skupien, J Trybul, I Matejko, B Mlynarski, W Malecki, MT AF Klupa, T. Solecka, I. Nowak, N. Szopa, M. Kiec-Wilk, B. Skupien, J. Trybul, I. Matejko, B. Mlynarski, W. Malecki, M. T. TI The Influence of Dietary Carbohydrate Content on Glycaemia in Patients with Glucokinase Maturity-onset Diabetes of the Young SO JOURNAL OF INTERNATIONAL MEDICAL RESEARCH LA English DT Article DE MATURITY-ONSET DIABETES OF THE YOUNG (MODY); MONOGENIC DIABETES; GLUCOKINASE (GCK); DIET; CARBOHYDRATE; GLYCAEMIC CONTROL ID HIGH PREVALENCE; BLOOD-GLUCOSE; TYPE-2 MODY-2; MUTATIONS; MELLITUS; DEFINITION; GENE AB Mutations in the glucokinase (GCK) gene result in maturity-onset diabetes of the young (MODY). Pharmacotherapy is not effective in GCK MODY. Thus, nutritional intervention seems to be the only therapeutic option. This study evaluated the effect of the quantity of dietary carbohydrate on glucose levels in 10 GCK mutation carriers: seven with MODY and three with prediabetes. All patients were exposed to high-carbohydrate diets for 2 days and then switched to low-carbohydrate diets (60% versus 25% of the daily calorie intake) for another 2 days, after a 1-day washout. Glucose levels were assessed by continuous blood glucose monitoring. In patients with GCK MODY on high-carbohydrate diets, glucose levels were significantly higher, and more hyperglycaemic episodes occurred, compared with patients on low-carbohydrate diets. This short-term observational study suggested that diets with a modestly limited carbohydrate content may improve glycaemic control in patients with GCK MODY. C1 [Klupa, T.; Nowak, N.; Szopa, M.; Kiec-Wilk, B.; Trybul, I.; Matejko, B.; Malecki, M. T.] Jagiellonian Univ, Coll Med, Dept Metab Dis, PL-31501 Krakow, Poland. [Szopa, M.] Jagiellonian Univ, Coll Med, Dept Med Educ, PL-31501 Krakow, Poland. [Klupa, T.; Solecka, I.; Szopa, M.; Kiec-Wilk, B.; Trybul, I.; Malecki, M. T.] Krakow Univ Hosp, Krakow, Poland. [Skupien, J.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Mlynarski, W.] Med Univ Lodz, Dept Paediat, Lodz, Poland. RP Malecki, MT (reprint author), Jagiellonian Univ, Coll Med, Dept Metab Dis, 15 Kopernika St, PL-31501 Krakow, Poland. EM malecki_malecki@yahoo.com FU EU [HEALTH-F2-2008-223211]; Jagiellonian University Medical College [K/ZDS/002310] FX This study was supported by the EU Framework 7 CEED3 grant (HEALTH-F2-2008-223211) and by funds from the Jagiellonian University Medical College (K/ZDS/002310). We are grateful to Ms Aleksandra Malecka for her editorial help in the preparation of the manuscript. NR 21 TC 4 Z9 4 U1 0 U2 1 PU FIELD HOUSE PUBLISHING LLP PI WORTHING PA 6 SOMPTING AVENUE, WORTHING, BN14 8HN, ENGLAND SN 0300-0605 J9 J INT MED RES JI J. Int. Med. Res. PD NOV-DEC PY 2011 VL 39 IS 6 BP 2296 EP 2301 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 887HC UT WOS:000299916500027 PM 22289546 ER PT J AU Finlayson, E Maselli, J Steinman, MA Rothberg, MB Lindenauer, PK Auerbach, AD AF Finlayson, Emily Maselli, Judith Steinman, Michael A. Rothberg, Michael B. Lindenauer, Peter K. Auerbach, Andrew D. TI Inappropriate Medication Use in Older Adults Undergoing Surgery: A National Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE surgery; potentially inappropriate medications (PIMs); older adults ID POTENTIALLY INAPPROPRIATE; ADMINISTRATIVE DATA; SURGICAL-PATIENTS; MEPERIDINE USE; HIP FRACTURE; DELIRIUM; OUTCOMES; INDICATORS; CRITERIA; IMPACT AB OBJECTIVES: To determine the prevalence and factors associated with use of potentially inappropriate medications (PIMs) in older adults undergoing surgery. DESIGN: Retrospective cohort study. SETTING: Three hundred seventy-nine acute care hospitals participating in the nationally representative Perspective database (2006-2008). PARTICIPANTS: Individuals aged 65 and older under going major inpatient gastrointestinal, gynecological, urological, and orthopedic surgery (N=272,351). MEASUREMENTS: Medications were classified as PIMs using previously published criteria defining 33 medications deemed potentially inappropriate in people aged 65 and older. Information about participant and provider characteristics and administration of PIMs was obtained from hospital discharge file data. Logistic regression techniques were used to examine factors associated with use of PIMs in the perioperative period. RESULTS: One-quarter of participants received at least one PIM during their surgical admission. Meperidine was the most frequently prescribed PIM (37,855, 14% of participants). In adjusted analysis, PIM use was less likely as age advanced (adjusted odds ratio (AOR) = 0.98 per year of age, 95% confidence interval (CI) = 0.97-0.98) and in men (AOR = 0.83, 95% CI = 0.81-0.85). PIMs were more likely to be prescribed to participants cared for by orthopedic surgeons than for those cared for by general surgeons (AOR = 1.22, 95% CI = 1.08-1.40). Participants undergoing surgery in the West (AOR = 1.79, 95% CI = 1.02-3.16) and South (AOR = 2.24, 95% CI = 1.38-3.64) were more likely to receive a PIM than those in the Northeast. CONCLUSION: Receipt of PIMs in older adults undergoing surgery is common and varies widely between providers and geographic regions and according to participant characteristics. Interventions aimed at reducing the use of PIMs in the perioperative period should be considered in quality improvement efforts. J Am Geriatr Soc 59:2139-2144, 2011. C1 [Finlayson, Emily] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94118 USA. [Finlayson, Emily] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94118 USA. [Maselli, Judith; Auerbach, Andrew D.] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94118 USA. [Steinman, Michael A.] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94118 USA. [Steinman, Michael A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Rothberg, Michael B.; Lindenauer, Peter K.] Baystate Med Ctr, Ctr Qual Care Res, Springfield, MA USA. [Rothberg, Michael B.; Lindenauer, Peter K.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. RP Finlayson, E (reprint author), Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, 3333 Calif St, San Francisco, CA 94118 USA. EM emily.finlayson@ucsfmedctr.org FU National Heart, Blood, Lund Institute [K24HL098372]; National Institute on Aging [K08AG028965]; American Federation for Aging Research [K23AG030999] FX Work on this study was funded in part by National Heart, Blood, Lund Institute Award K24HL098372 to Dr. Auerbach. Dr. Finlayson was supported by National Institute on Aging/Paul B. Beeson Clinical Scientist Development Award in Aging K08AG028965. Dr. Steinman was supported by the National Institute on Aging and the American Federation for Aging Research (K23AG030999). NR 23 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2011 VL 59 IS 11 BP 2139 EP 2144 DI 10.1111/j.1532-5415.2011.03567.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 853FG UT WOS:000297411000020 PM 21883113 ER PT J AU Wong, CH Landefeld, CS AF Wong, Chek Hooi Landefeld, C. Seth TI Academic Geriatrics in Singapore SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE education; research; geriatrics ID CARE; MEDICINE; POPULATION; EDUCATION AB Singapore is one of the fastest-aging countries in the world. The proportion of adults aged 65 and older is projected to increase from 8.7% to 20% over the next 20 years. The country has developed various strategies to meet the needs of this increase in older adults. There is an acute shortage of geriatricians and a need to train more healthcare workers to care for older adults. Geriatric medicine is a relatively new specialty, and a small number of geriatricians have been tasked with providing an increasing load of clinical service, education, and research. Hence, there is a need to develop a cohesive structure of support for faculty development and retention, advanced specialty trainee recruitment, leadership in medical education, research, and clinical service to care for the rapidly aging population. In addition, geriatric medicine is primarily a hospital-based specialty in Singapore. There is still opportunity to collaborate and improve the academic and practice integration of geriatric medicine into primary care and intermediate and long-term care where it is most needed. J Am Geriatr Soc 59:2145-2150, 2011. C1 [Wong, Chek Hooi] Khoo Teck Puat Hosp, Dept Geriatr Med, Singapore 768828, Singapore. [Landefeld, C. Seth] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Landefeld, C. Seth] San Francisco VA Med Ctr, San Francisco, CA USA. RP Wong, CH (reprint author), Khoo Teck Puat Hosp, Dept Geriatr Med, 90 Yishun Cent, Singapore 768828, Singapore. EM chekhooi@yahoo.com FU U.S., Department of State, Bureau of Educational and Cultural Affairs FX Chek Hooi Wong and C. Seth Landefeld both state no financial interest, stock, or derived direct financial benefit. Chek Hooi Wong was funded by a Fulbright Singapore Researcher Program, U.S., Department of State, Bureau of Educational and Cultural Affairs. NR 22 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2011 VL 59 IS 11 BP 2145 EP 2150 DI 10.1111/j.1532-5415.2011.03630.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 853FG UT WOS:000297411000021 PM 22091794 ER PT J AU Gray, AN Henderson-Frost, JM Boyd, D Shirafi, S Niki, H Goldberg, MB AF Gray, Andrew N. Henderson-Frost, Josephine M. Boyd, Dana Shirafi, Shirin Niki, Hironori Goldberg, Marcia B. TI Unbalanced Charge Distribution as a Determinant for Dependence of a Subset of Escherichia coli Membrane Proteins on the Membrane Insertase YidC SO MBIO LA English DT Article ID F1F0 ATP SYNTHASE; INNER MEMBRANE; SUBUNIT-C; CYTOPLASMIC MEMBRANE; TOPOLOGY; BIOGENESIS; SEC; COMPLEXES; DEPLETION; PROTEOME AB Membrane proteins are involved in numerous essential cell processes, including transport, gene regulation, motility, and metabolism. To function properly, they must be inserted into the membrane and folded correctly. YidC, an essential protein in Escherichia coli with homologues in other bacteria, Archaea, mitochondria, and chloroplasts, functions by incompletely understood mechanisms in the insertion and folding of certain membrane proteins. Using a genome-scale approach, we identified 69 E. coli membrane proteins that, in the absence of YidC, exhibited aberrant localization by microscopy. Further examination of a subset revealed biochemical defects in membrane insertion in the absence of YidC, indicating their dependence on YidC for proper membrane insertion or folding. Membrane proteins possessing an unfavorable distribution of positively charged residues were significantly more likely to depend on YidC for membrane insertion. Correcting the charge distribution of a charge-unbalanced YidC-dependent membrane protein abrogated its requirement for YidC, while perturbing the charge distribution of a charge-balanced YidC-independent membrane protein rendered it YidC dependent, demonstrating that charge distribution can be a necessary and sufficient determinant of YidC dependence. These findings provide insights into a mechanism by which YidC promotes proper membrane protein biogenesis and suggest a critical function of YidC in all organisms and organelles that express it. IMPORTANCE Biological membranes are fundamental components of cells, providing barriers that enclose the cell and separate compartments. Proteins inserted into biological membranes serve critical functions in molecular transport, molecular partitioning, and other essential cell processes. The mechanisms involved in the insertion of proteins into membranes, however, are incompletely understood. The YidC protein is critical for the insertion of a subset of proteins into membranes across an evolutionarily wide group of organisms. Here we identify a large group of proteins that depend on YidC for membrane insertion in Escherichia coli, and we identify unfavorable distribution of charge as an important determinant of YidC dependence for proper membrane insertion. C1 [Gray, Andrew N.; Boyd, Dana; Goldberg, Marcia B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Henderson-Frost, Josephine M.; Shirafi, Shirin; Goldberg, Marcia B.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA USA. [Niki, Hironori] Natl Inst Genet, Ctr Genet Resource Informat, Mishima, Shizuoka 411, Japan. RP Goldberg, MB (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. EM mgoldberg1@partners.org FU NIH [AI035817]; Ministry of Education, Culture, Sports, Science, and Technology of Japan FX This work was supported by NIH grant AI035817 (to M.B.G.) and by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to H.N.). NR 46 TC 5 Z9 5 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD NOV-DEC PY 2011 VL 2 IS 6 AR e00238-11 DI 10.1128/mBio.00238-11 PG 10 WC Microbiology SC Microbiology GA 888GV UT WOS:000299992700012 ER PT J AU Beeri, MS Moshier, E Schmeidler, J Godbold, J Uribarri, J Reddy, S Sano, M Grossman, HT Cai, WJ Vlassara, H Silverman, JM AF Beeri, Michal Schnaider Moshier, Erin Schmeidler, James Godbold, James Uribarri, Jaime Reddy, Sarah Sano, Mary Grossman, Hillel T. Cai, Weijing Vlassara, Helen Silverman, Jeremy M. TI Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE Methylglyoxal; Advanced glycation end products; Type 2 diabetes; Cognitive decline; Alzheimer's disease ID ADVANCED GLYCATION ENDPRODUCTS; ALZHEIMERS-DISEASE; CARBONYL SCAVENGERS; CEREBROSPINAL-FLUID; PROTEIN GLYCATION; OXIDATIVE STRESS; OLDEST-OLD; DEMENTIA; AGE; NEUROPATHOLOGY AB Background: Advanced glycations end products increase oxidant stress, inflammation, and neurotoxicity. Serum levels are increased in diabetes and aging. We examined the relationship between serum methylglyoxal derivatives (sMG), and cognitive decline, in 267 non-demented elderly. Methods: Tobit mixed regression models assessed the association of baseline sMG with cognitive decline in the Mini Mental State Exam (MMSE) over time, controlling for sociodemographic factors (age, sex, and years of education), cardiovascular risk factors (diabetes and presence of an ApoE4 allele), and kidney function. sMG was assessed by ELISA. Results: The fully adjusted model showed an annual decline of 0.26 MMSE points per unit increase in baseline sMG (p = 0.03). Significance was unchanged as additional risk factors were added to the model. The interactions of sMG with diabetes, sex, age, kidney function, and ApoE4 genotype were not significant. Conclusions: Higher levels of baseline sMG were associated with a faster rate of cognitive decline, after adjusting for several sociodemographic and clinical characteristics. This relationship did not differ by sex, ApoE4 genotype, or diabetes status suggesting its generality. Since subjects were cognitively normal at the beginning of the study, elevated sMG may be indicative of brain cell injury initiated before clinically evident cognitive compromise. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Beeri, Michal Schnaider; Schmeidler, James; Reddy, Sarah; Sano, Mary; Grossman, Hillel T.; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Moshier, Erin; Godbold, James] Mt Sinai Sch Med, Dept Biostat, New York, NY 10029 USA. [Uribarri, Jaime] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Cai, Weijing; Vlassara, Helen] Mt Sinai Sch Med, Dept Geriatr, New York, NY 10029 USA. [Beeri, Michal Schnaider; Sano, Mary] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Beeri, MS (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave Levy Pl,Box 1230, New York, NY 10029 USA. EM michal.beeri@mssm.edu FU NIA [K01 AG023515-01, R01 AG034087, P01 AG02219, P50 AG05138, R37AG023188]; Irma T. Hirschl Award; Berkman Trust FX Supported by NIA grants K01 AG023515-01 and R01 AG034087 to Dr. Beeri, Project 4 in P01 AG02219 to Dr. Silverman, P50 AG05138 to Dr. Mary Sano, and R37AG023188 (MERIT) to Dr. Vlassara, as well as by the Irma T. Hirschl Award to Dr. Beeri and the Berkman Trust to Dr. Vahram Haroutunian. NR 39 TC 32 Z9 32 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD NOV-DEC PY 2011 VL 132 IS 11-12 BP 583 EP 587 DI 10.1016/j.mad.2011.10.007 PG 5 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 888CG UT WOS:000299980800007 PM 22079406 ER PT J AU Baraghis, E Bolduc, V Lefebvre, J Srinivasan, VJ Boudoux, C Thorin, E Lesage, F AF Baraghis, E. Bolduc, V. Lefebvre, J. Srinivasan, V. J. Boudoux, C. Thorin, E. Lesage, F. TI Measurement of cerebral microvascular compliance in a model of atherosclerosis with optical coherence tomography SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID ALZHEIMERS-DISEASE; BLOOD-FLOW; ANGIOGRAPHY; BRAIN AB Optical coherence tomography (OCT) has recently been used to produce 3D angiography of microvasculature and blood flow maps of large vessels in the rodent brain in-vivo. However, use of this optical method for the study of cerebrovascular disease has not been fully explored. Recent developments in neurodegenerative diseases has linked common cardiovascular risk factors to neurodegenerative risk factors hinting at a vascular hypothesis for the development of the latter. Tools for studying cerebral blood flow and the myogenic tone of cerebral vasculature have thus far been either highly invasive or required ex-vivo preparations therefore not preserving the delicate in-vivo conditions. We propose a novel technique for reconstructing the flow profile over a single cardiac cycle in order to evaluate flow pulsatility and vessel compliance. A vascular model is used to simulate changes in vascular compliance and interpret OCT results. Comparison between atherosclerotic and wild type mice show a trend towards increased compliance in the smaller arterioles of the brain (diameter < 80 mu m) in the disease model. These results are consistent with previously published ex-vivo work confirming the ability of OCT to investigate vascular dysfunction. (C) 2011 Optical Society of America C1 [Baraghis, E.; Lefebvre, J.; Boudoux, C.; Lesage, F.] Ecole Polytech Montreal, Montreal, PQ H3C 3A7, Canada. [Bolduc, V.; Thorin, E.; Lesage, F.] Montreal Heart Inst, Res Ctr, Montreal, PQ H3T 1J4, Canada. [Srinivasan, V. J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Opt Div, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. RP Baraghis, E (reprint author), Ecole Polytech Montreal, 2500 Chemin Polytech, Montreal, PQ H3C 3A7, Canada. EM frederic.lesage@polymtl.ca RI Boudoux, Caroline/A-6399-2012 FU Fonds de la recherche en sante du Quebec; Natural Sciences and Engineering Research Council of Canada (NSERC); National Institutes of Health [K99NS067050]; American Heart Association [11IRG5440002] FX E. Baraghis was supported by scholarships from the "Fonds de la recherche en sante du Quebec" and the Natural Sciences and Engineering Research Council of Canada (NSERC). F. Lesage, C. Boudoux were supported NSERC Discovery grants. V. J. Srinivasan was supported by the National Institutes of Health (K99NS067050) and the American Heart Association (11IRG5440002) NR 20 TC 4 Z9 4 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD NOV 1 PY 2011 VL 2 IS 11 BP 3079 EP 3093 PG 15 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 886WB UT WOS:000299883500014 PM 22076269 ER PT J AU Xu, ZP Dong, YL Wu, X Zhang, J McAuliffe, S Pan, CX Zhang, YY Ichinose, F Yue, Y Xie, ZC AF Xu, Zhipeng Dong, Yuanlin Wu, Xu Zhang, Jun McAuliffe, Sayre Pan, Chuxiong Zhang, Yiying Ichinose, Fumito Yue, Yun Xie, Zhongcong TI The Potential Dual Effects of Anesthetic Isoflurane on A beta-Induced Apoptosis SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Anesthesia; Alzheimer's disease; isoflurane; apoptosis; beta-Amyloid protein; dual effects; cytosolic calcium ID AMYLOID PRECURSOR PROTEIN; INDUCED NEURONAL APOPTOSIS; ALZHEIMERS-DISEASE; ENDOPLASMIC-RETICULUM; HIPPOCAMPAL-NEURONS; INTRACELLULAR CA2+; CELL-DEATH; CASPASE-3 ACTIVATION; GLUCOSE DEPRIVATION; PROAPOPTOTIC BAX AB beta-amyloid protein (A beta)-induced neurotoxicity is the main component of Alzheimer's disease (AD) neuropathogenesis. Inhalation anesthetics have long been considered to protect against neurotoxicity. However, recent research studies have suggested that the inhalation anesthetic isoflurane may promote neurotoxicity by inducing apoptosis and increasing A beta levels. We therefore set out to determine whether isoflurane can induce dose-and time-dependent dual effects on A beta-induced apoptosis: protection versus promotion. H4 human neuroglioma cells, primary neurons from nave mice, and nave mice were treated with A beta and/or isoflurane, and levels of caspase-3 cleavage (activation), apoptosis, Bcl-2, Bax, and cytosolic calcium were determined. Here we show for the first time that the treatment with 2% isoflurane for six hours or 30 minutes potentiated, whereas the treatment with 0.5% isoflurane for six hours or 30 minutes attenuated, the A beta-induced caspase-3 activation and apoptosis in vitro. Moreover, anesthesia with 1.4% isoflurane for two hours potentiated, whereas the anesthesia with 0.7% isoflurane for 30 minutes attenuated, the A beta-induced caspase-3 activation in vivo. The high concentration isoflurane potentiated the A beta-induced reduction in Bcl-2/Bax ratio and caused a robust elevation of cytosolic calcium levels. The low concentration isoflurane attenuated the A beta-induced reduction in Bcl-2/Bax ratio and caused only a mild elevation of cytosolic calcium levels. These results suggest that isoflurane may have dual effects (protection or promotion) on A beta-induced toxicity, which potentially act through the Bcl-2 family proteins and cytosolic calcium. These findings would lead to more systematic studies to determine the potential dual effects of anesthetics on AD-associated neurotoxicity. C1 [Xu, Zhipeng; Dong, Yuanlin; Wu, Xu; Zhang, Jun; McAuliffe, Sayre; Pan, Chuxiong; Zhang, Yiying; Xie, Zhongcong] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Anesthesia Crit Care & Pain Med,Dept Neurol, Geriatr Anesthesia Res Unit,Genet & Aging Res Uni, Charlestown, MA 02129 USA. [Xu, Zhipeng; Dong, Yuanlin; Wu, Xu; Zhang, Jun; McAuliffe, Sayre; Pan, Chuxiong; Zhang, Yiying; Ichinose, Fumito; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Wu, Xu] China Med Univ, Fac Forens Med, Dept Forens Pathol, Shenyang 110001, Peoples R China. [Zhang, Jun] Fudan Univ, Dept Anesthesiol, Huashan Hosp, Shanghai 200041, Peoples R China. [Pan, Chuxiong] Capital Med Univ, Beijing Tongren Hosp, Dept Anesthesia, Beijing 100050, Peoples R China. [Yue, Yun] Capital Med Univ, Beijing Chaoyang Hosp, Dept Anesthesia, Beijing 100020, Peoples R China. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Anesthesia Crit Care & Pain Med,Dept Neurol, Geriatr Anesthesia Res Unit,Genet & Aging Res Uni, 149 13th St,4310, Charlestown, MA 02129 USA. EM zxie@partners.org FU National Institutes of Health [K08NS048140, R21AG029856, R01 GM088801, R01GM079360]; American Geriatrics Society; Alzheimer's Association; China National Science Foundation [NSF30928026] FX This research was supported by K08NS048140, R21AG029856 and R01 GM088801 (National Institutes of Health), Jahnigen Career Development Award (American Geriatrics Society), Investigator Initiated Research Grant (Alzheimer's Association) (to Z. X.), R01GM079360 (National Institutes of Health) (to FI), and China National Science Foundation Oversea young scholar collaboration research award NSF30928026 (to Y.Y. and Z. X.). NR 57 TC 20 Z9 21 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 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD NOV PY 2011 VL 8 IS 7 BP 741 EP 752 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 882PI UT WOS:000299575700004 PM 21244349 ER PT J AU Hirsch, AE Yoo, AJ Hirsch, JA AF Hirsch, Ariel E. Yoo, Albert J. Hirsch, Joshua A. TI In Response: Timing of EBRT Did Not Affect Outcome SO PAIN PHYSICIAN LA English DT Letter C1 [Hirsch, Ariel E.] Boston Univ, Med Ctr, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02118 USA. [Yoo, Albert J.; Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Div Intervent Neuroradiol, Boston, MA 02114 USA. RP Hirsch, AE (reprint author), Boston Univ, Med Ctr, Dept Radiat Oncol, Massachusetts Gen Hosp, 830 Harrison Ave,Moakley Bldg LL, Boston, MA 02118 USA. EM Ariel.hirsch@bmc.org; jahirsch@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD NOV-DEC PY 2011 VL 14 IS 6 BP 570 EP 570 PG 1 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 885NC UT WOS:000299784700011 ER PT J AU Basu, A Jena, AB Philipson, TJ AF Basu, A. Jena, A. B. Philipson, T. J. TI THE IMPACT OF COMPARATIVE EFFECTIVENESS RESEARCH ON HEALTH AND HEALTH CARE SPENDING SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Basu, A.] Univ Washington, Seattle, WA 98195 USA. [Jena, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Philipson, T. J.] Univ Chicago, Chicago, IL 60637 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 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV PY 2011 VL 14 IS 7 BP A301 EP A301 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 876KT UT WOS:000299107100356 ER PT J AU Chan, K Lai, MN Groessl, EJ Hanchate, A Hernandez, L Wong, JB Clark, JA Asch, S Gifford, AL Ho, S AF Chan, K. Lai, M. N. Groessl, E. J. Hanchate, A. Hernandez, L. Wong, J. B. Clark, J. A. Asch, S. Gifford, A. L. Ho, S. TI POTENTIAL COSTS ASSOCIATED WITH NEW DIRECT ACTING ANTIVIRAL (DAAS) THERAPY FOR UNTREATED CHRONIC HEPATITIS C GENOTYPE 1 INFECTION IN THE VETERANS HEALTH ADMINISTRATION SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Chan, K.; Hanchate, A.; Hernandez, L.; Clark, J. A.] Boston Univ, Boston, MA 02215 USA. [Lai, M. N.; Ho, S.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Groessl, E. J.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Wong, J. B.] Tufts Univ, Boston, MA 02111 USA. [Asch, S.] VA Greater Los Angeles Healthcare Syst GLA, Los Angeles, CA USA. [Gifford, A. L.] Edith Nourse Rogers Mem Vet Adm Hosp, Bedford, MA 01730 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV PY 2011 VL 14 IS 7 BP A269 EP A270 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 876KT UT WOS:000299107100193 ER PT J AU Jena, AB Philipson, TJ AF Jena, A. B. Philipson, T. J. TI ENDOGENOUS COST-EFFECTIVENESS ANALYSIS IN HEALTH CARE TECHNOLOGY ADOPTION SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Jena, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Philipson, T. J.] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV PY 2011 VL 14 IS 7 BP A363 EP A364 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 876KT UT WOS:000299107100688 ER PT J AU Negrier, S Bushmakin, AG Cappelleri, JC Charbonneau, C Sandin, R Michaelson, MD Figlin, RA Motzer, RJ AF Negrier, S. Bushmakin, A. G. Cappelleri, J. C. Charbonneau, C. Sandin, R. Michaelson, M. D. Figlin, R. A. Motzer, R. J. TI USING A WEIBULL PARAMETRIC MODEL FOR FAILURE-TIME DATA TO ASSESS PROGRESSION-FREE SURVIVAL AS A SURROGATE ENDPOINT FOR OVERALL SURVIVAL IN A TRIAL OF PATIENTS WITH METASTATIC RENAL CELL CARCINOMA SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Negrier, S.] Ctr Leon Berard, F-69373 Lyon, France. [Bushmakin, A. G.; Cappelleri, J. C.] Pfizer Inc, Groton, CT 06340 USA. [Charbonneau, C.] Pfizer Oncol, Global Outcomes Res, New York, NY USA. [Sandin, R.] Pfizer Oncol, Global Hlth Econ & Outcomes Res, Stockholm, Sweden. [Michaelson, M. D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Figlin, R. A.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Motzer, R. J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 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 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV PY 2011 VL 14 IS 7 BP A471 EP A471 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 876KT UT WOS:000299107101372 ER PT J AU Denis, TGS Dai, TH Izikson, L Astrakas, C Anderson, RR Hamblin, MR Tegos, GP AF Denis, Tyler G. St. Dai, Tianhong Izikson, Leonid Astrakas, Christos Anderson, Richard Rox Hamblin, Michael R. Tegos, George P. TI All you need is light Antimicrobial photoinactivation as an evolving and emerging discovery strategy against infectious disease SO VIRULENCE LA English DT Review DE photodynamic inactivation and therapy; photosensitizer; reactive oxygen species; permeability barrier; multidrug efflux systems; biofilms; drug delivery; nanomedicine; antimicrobial resistance; clinical applications ID STAPHYLOCOCCUS-EPIDERMIDIS BIOFILMS; GRAM-NEGATIVE BACTERIA; TOLUIDINE-BLUE-O; MEDIATED PHOTODYNAMIC INACTIVATION; RESISTANT ACINETOBACTER-BAUMANNII; MYCOBACTERIUM-BOVIS BCG; N-METHYL-PYRIDYL; PSEUDOMONAS-AERUGINOSA; IN-VITRO; MULTIDRUG-RESISTANCE AB The story of prevention and control of infectious diseases remains open and a series of highly virulent pathogens are emerging both in and beyond the hospital setting. Antibiotics were an absolute success story for a previous era. The academic and industrial biomedical communities have now come together to formulate consensus beliefs regarding the pursuit of novel and effective alternative anti-infective countermeasures. Photodynamic therapy was established and remains a successful modality for malignancies but photodynamic inactivation has been transformed recently to an antimicrobial discovery and development platform. The concept of photodynamic inactivation is quite straightforward and requires microbial exposure to light energy, typically wavelengths in the visible region, that causes the excitation of photosensitizer molecules (either exogenous or endogenous), which results in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation. It is an area of increasing interest, as research is advancing (1) to identify the photochemical and photophysical mechanisms involved in inactivation, (2) to develop potent and clinically compatible photosensitizer, (3) to understand how photoinactivation is affected by key microbial phenotypic elements (multidrug resistance and efflux, virulence and pathogenesis determinants, biofilms), (4) to explore novel delivery platforms inspired by current trends in pharmacology and nanotechnology and (5) to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants. C1 [Denis, Tyler G. St.; Dai, Tianhong; Izikson, Leonid; Anderson, Richard Rox; Hamblin, Michael R.; Tegos, George P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Denis, Tyler G. St.] Columbia Univ, New York, NY USA. [Dai, Tianhong; Izikson, Leonid; Anderson, Richard Rox; Hamblin, Michael R.; Tegos, George P.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Astrakas, Christos] Democritus Univ, Thrace Med Sch, Div Internal Med, Alexandroupolis, Greece. [Anderson, Richard Rox; Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tegos, George P.] Univ New Mexico, Sch Med, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Tegos, George P.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. RP Tegos, GP (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM gtegos@salud.unm.edu OI Hamblin, Michael/0000-0001-6431-4605 FU Columbia University; NIH [5U54MH084690-02, RO1 AI050875]; US Air Force MFEL [FA9550-04-1-0079]; Bullock-Wellman Fellowship Award; Airlift Research Foundation [109421] FX Research conducted by Tyler G. St. Denis was supported by the Columbia University I. I. Rabi Fellows Program. George P. Tegos is supported by the NIH (grant 5U54MH084690-02). Research conducted in the Hamblin Laboratory was supported by NIH (RO1 AI050875 to M. R. H.) and US Air Force MFEL Program (FA9550-04-1-0079). T. D. was partially supported by a Bullock-Wellman Fellowship Award and an Airlift Research Foundation Extremity Trauma Research Grant (grant 109421). NR 158 TC 16 Z9 19 U1 1 U2 41 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 J9 VIRULENCE JI Virulence PD NOV-DEC PY 2011 VL 2 IS 6 BP 509 EP 520 DI 10.4161/viru.2.6.17889 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 878MP UT WOS:000299261500005 ER PT J AU Chand, NS Hung, DT AF Chand, Nikhilesh S. Hung, Deborah T. TI The two-component sensor kinase KinB acts as a non-canonical switch between acute and chronic infection SO VIRULENCE LA English DT Article DE Pseudomonas aeruginosa; two-component systems; regulation; KinB ID PSEUDOMONAS-AERUGINOSA INFECTION; SIGNAL-TRANSDUCTION; REGULATORY SYSTEMS; VIRULENCE FACTORS; HISTIDINE KINASES; MODEL; PATHOGENESIS; PHOSPHORYLATION; IDENTIFICATION; RESISTANCE C1 [Chand, Nikhilesh S.; Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Chand, Nikhilesh S.; Hung, Deborah T.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Chand, Nikhilesh S.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Chand, Nikhilesh S.; Hung, Deborah T.] MIT & Harvard, Broad Inst, Cambridge, MA USA. [Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA USA. RP Hung, DT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM hung@molbio.mgh.harvard.edu NR 38 TC 2 Z9 2 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 J9 VIRULENCE JI Virulence PD NOV-DEC PY 2011 VL 2 IS 6 BP 553 EP 558 DI 10.4161/viru.2.6.17987 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 878MP UT WOS:000299261500011 PM 21971182 ER PT J AU Yu, LY Hales, CA AF Yu, Lunyin Hales, Charles A. TI Silencing of Sodium-Hydrogen Exchanger 1 Attenuates the Proliferation, Hypertrophy, and Migration of Pulmonary Artery Smooth Muscle Cells via E2F1 SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE sodium-hydrogen exchanger 1; E2F1; PASMC proliferation; hypertrophy; hypoxia ID CARDIAC MYOCYTE HYPERTROPHY; NA+/H+-EXCHANGER; ENDOTHELIAL-CELLS; INTRACELLULAR PH; GENE-EXPRESSION; HEART-FAILURE; HYPOXIA; HYPERTENSION; INHIBITION; HEPARIN AB We previously found that deficiency of the sodium-hydrogen exchanger 1 (NHE1) gene prevented hypoxia-induced pulmonary hypertension and vascular remodeling in mice, which were accompanied by a significantly reduced proliferation of pulmonary artery smooth muscle cells(PASMCs), and which decreased the medial-wall thickness of pulmonary arteries. That finding indicated the involvement of NHE1 in the proliferation and hypertrophy of PASMCs, but the underlying mechanism was not fully understood. To define the mechanism by which the inhibition of NHE1 decreases hypoxic pulmonary hypertension and vascular remodeling, we investigated the role of E2F1, a nuclear transcription factor, in silencing the NHE1 gene-induced inhibition of the proliferation, hypertrophy, and migration of human PASMCs. We found that: (1) silencing of NHE1 by short, interfering RNA (siRNA) significantly inhibited PASMC proliferation and cell cycle progression, decreased hypoxia-induced hypertrophy (in terms of cell size and protein/DNA ratio) and migration (in terms of the wound-healing and migration chamber assays); (2) hypoxia induced the expression of E2F1, which was reversed by NHE1 siRNA; and (3) the overexpression of E2F1 blocked the inhibitory effect of NHE1 siRNA on the proliferation, hypertrophy, and migration of PASMCs. The present study determined that silencing the NHE1 gene significantly inhibited the hypoxia-induced proliferation, hypertrophy, and migration of human PASMCs via repression of the nuclear transcription factor E2F1. This study revealed a novel mechanism underlying the regulation of hypoxic pulmonary hypertension and vascular remodeling via NHE1. C1 [Yu, Lunyin; Hales, Charles A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA 02114 USA. RP Yu, LY (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 lyu3@partners.org FU American Thoracic Society [PH-08-010]; National Institutes of Health [HL39150]; Susannah Wood Foundation FX This work was supported by American Thoracic Society/Pulmonary Hypertension Research Grant PH-08-010 (L.Y.), by National Institutes of Health grant HL39150 (C. A. H.), and by the Susannah Wood Foundation. NR 49 TC 25 Z9 25 U1 2 U2 5 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD NOV PY 2011 VL 45 IS 5 BP 923 EP 930 DI 10.1165/rcmb.2011-0032OC PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 884CF UT WOS:000299681800004 PM 21454803 ER PT J AU Hang, JQ Lee, MS Zhang, FY Zheng, BY Su, L Yang, Z Dai, HL Zhang, HX Christiani, DC AF Hang, J-Q Lee, M-S Zhang, F-Y Zheng, B-Y Su, L. Yang, Z. Dai, H-L Zhang, H-X Christiani, David C. TI HOUSEHOLD SOLID FUEL USE, BODY MASS INDEX, AND LUNG FUNCTION SO RESPIROLOGY LA English DT Meeting Abstract C1 [Lee, M-S; Su, L.; Zhang, H-X; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Environm & Occupat Med & Epidemiol Program, Dept Environm Hlth, Boston, MA 02115 USA. [Hang, J-Q; Zhang, F-Y; Zheng, B-Y; Dai, H-L] Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China. [Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christiani, David C.] 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 1323-7799 J9 RESPIROLOGY JI Respirology PD NOV PY 2011 VL 16 SU 2 SI SI BP 42 EP 42 PG 1 WC Respiratory System SC Respiratory System GA 868SZ UT WOS:000298547100137 ER PT J AU Enzler, T Sano, Y Choo, MK Cottam, HB Karin, M Tsao, H Park, JM AF Enzler, Thomas Sano, Yasuyo Choo, Min-Kyung Cottam, Howard B. Karin, Michael Tsao, Hensin Park, Jin Mo TI Cell-Selective Inhibition of NF-kappa B Signaling Improves Therapeutic Index in a Melanoma Chemotherapy Model SO CANCER DISCOVERY LA English DT Article ID METASTATIC MALIGNANT-MELANOMA; IKK-BETA; MOUSE MODEL; LIPOSOMAL DOXORUBICIN; MACROPHAGE APOPTOSIS; PHASE-II; KINASE; CANCER; INFLAMMATION; ACTIVATION AB The transcription factor NF-kappa B promotes the survival of cancer cells exposed to doxorubicin and other chemotherapeutic agents. I kappa B kinase is essential for chemotherapy-induced NF-kappa B activation and considered a prime target for anticancer treatment. An I kappa B kinase inhibitor sensitized human melanoma xenografts in mice to killing by doxorubicin yet also exacerbated treatment toxicity in the host animals. By using mouse models that simulate cell-selective targeting, we found that impaired NF-kappa B activation in melanoma and host myeloid cells accounts for therapeutic and adverse effects, respectively. Ablation of tumor-intrinsic NF-kappa B activity resulted in apoptosis-driven tumor regression after treatment with doxorubicin. By contrast, chemotherapy in mice with myeloid-specific loss of NF-kappa B activation led to a massive intratumoral recruitment of interleukin-1 beta-producing neutrophils and necrotic tumor lesions, a condition associated with increased host mortality but not accompanied by tumor regression. Therefore, a molecular target-based therapy may be steered toward different clinical outcomes depending on the drug's cell-specific effects. SIGNIFICANCE: Our findings show that the I kappa B kinase-NF-kappa B signaling pathway is important for both promoting treatment resistance and preventing host toxicity in cancer chemotherapy; however, the two functions are exerted by distinct cell type-specific mechanisms and can therefore be selectively targeted to achieve an improved therapeutic outcome. Cancer Discovery; 1(6); 496-507. (C) 2011 AACR. C1 [Enzler, Thomas; Sano, Yasuyo; Choo, Min-Kyung; Park, Jin Mo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Enzler, Thomas; Sano, Yasuyo; Choo, Min-Kyung; Park, Jin Mo] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tsao, Hensin] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. [Tsao, Hensin; Park, Jin Mo] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Tsao, Hensin; Park, Jin Mo] Harvard Univ, Sch Med, Boston, MA USA. [Enzler, Thomas] Univ Med Goettingen, Dept Hematol & Oncol, Gottingen, Germany. [Enzler, Thomas; Karin, Michael] Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA. [Cottam, Howard B.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. RP Park, JM (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM jmpark@cbrc2.mgh.harvard.edu FU Cutaneous Biology Research Center-Wellman Center for Photomedicine FX This work was supported by the Cutaneous Biology Research Center-Wellman Center for Photomedicine Collaborative Project (J.M. Park). NR 48 TC 17 Z9 17 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD NOV PY 2011 VL 1 IS 6 BP 496 EP 507 DI 10.1158/2159-8290.CD-11-0143 PG 12 WC Oncology SC Oncology GA 880MR UT WOS:000299411700029 PM 22389871 ER PT J AU Tanaka, K Babic, I Nathanson, D Akhavan, D Guo, DL Gini, B Dang, J Zhu, SJ Yang, HJ De Jesus, J Amzajerdi, AN Zhang, YN Dibble, CC Dan, HC Rinkenbaugh, A Yong, WH Vinters, HV Gera, JF Cavenee, WK Cloughesy, TF Manning, BD Baldwin, AS Mischel, PS AF Tanaka, Kazuhiro Babic, Ivan Nathanson, David Akhavan, David Guo, Deliang Gini, Beatrice Dang, Julie Zhu, Shaojun Yang, Huijun De Jesus, Jason Amzajerdi, Ali Nael Zhang, Yinan Dibble, Christian C. Dan, Hancai Rinkenbaugh, Amanda Yong, William H. Vinters, Harry V. Gera, Joseph F. Cavenee, Webster K. Cloughesy, Timothy F. Manning, Brendan D. Baldwin, Albert S. Mischel, Paul S. TI Oncogenic EGFR Signaling Activates an mTORC2-NF-kappa B Pathway That Promotes Chemotherapy Resistance SO CANCER DISCOVERY LA English DT Article ID NF-KAPPA-B; GROWTH-FACTOR RECEPTOR; MTOR COMPLEX 2; MAMMALIAN TARGET; MOTIF PHOSPHORYLATION; GLIOBLASTOMA PATIENTS; KINASE INHIBITORS; CANCER-THERAPY; AKT; RICTOR AB Although it is known that mTOR complex 2 (mTORC2) functions upstream of Akt, the role of this protein kinase complex in cancer is not well understood. Through an integrated analysis of cell lines, in vivo models, and clinical samples, we demonstrate that mTORC2 is frequently activated in glioblastoma (GBM), the most common malignant primary brain tumor of adults. We show that the common activating epidermal growth factor receptor (EGFR) mutation (EGFRvIII) stimulates mTORC2 kinase activity, which is partially suppressed by PTEN. mTORC2 signaling promotes GBM growth and survival and activates NF-kappa B. Importantly, this mTORC2-NF-kappa B pathway renders GBM cells and tumors resistant to chemotherapy in a manner independent of Akt. These results highlight the critical role of mTORC2 in the pathogenesis of GBM, including through the activation of NF-kappa B downstream of mutant EGFR, leading to a previously unrecognized function in cancer chemotherapy resistance. These findings suggest that therapeutic strategies targeting mTORC2, alone or in combination with chemotherapy, will be effective in the treatment of cancer. SIGNIFICANCE: This study demonstrates that EGFRvIII-activated mTORC2 signaling promotes GBM proliferation, survival, and chemotherapy resistance through Akt-independent activation of NF-kappa B. These results highlight the role of mTORC2 as an integrator of two canonical signaling networks that are commonly altered in cancer, EGFR/phosphoinositide-3 kinase (PI3K) and NF-kappa B. These results also validate the importance of mTORC2 as a cancer target and provide new insights into its role in mediating chemotherapy resistance, suggesting new treatment strategies. Cancer Discovery; 1(6); 524-38. (C) 2011 AACR. C1 [Mischel, Paul S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Ctr Hlth Sci, Los Angeles, CA 90095 USA. [Mischel, Paul S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Yong, William H.; Cloughesy, Timothy F.; Mischel, Paul S.] Univ Calif Los Angeles, David Geffen Sch Med, Henry Singleton Brain Tumor Program, Los Angeles, CA 90095 USA. [Yong, William H.; Cloughesy, Timothy F.; Mischel, Paul S.] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Vinters, Harry V.; Cloughesy, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Gera, Joseph F.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Res & Dev, Sepulveda, CA USA. [Guo, Deliang] Ohio State Univ, Sch Med, Dept Radiat Oncol, Arthur G James Comprehens Canc Ctr, Columbus, OH 43210 USA. [Cavenee, Webster K.] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. [Zhang, Yinan; Dibble, Christian C.; Manning, Brendan D.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Dan, Hancai; Rinkenbaugh, Amanda; Baldwin, Albert S.] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. RP Mischel, PS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Ctr Hlth Sci, 10833 Le Conte Ave,Room 13-321, Los Angeles, CA 90095 USA. EM pmischel@mednet.ucla.edu RI Guo, Deliang/I-3735-2014; Zhang, Yinan/N-6432-2014; OI Guo, Deliang/0000-0002-8359-390X; Zhang, Yinan/0000-0002-3471-6598; Nael, Ali/0000-0002-9671-5531 FU NIH [CA119347, NS73831, P01-CA95616, CA122617, CA75080, CA73756]; Accelerate Brain Cancer Cure; STOP Cancer; Fred Miller Family; John W. Carson Foundation; Lya and Harrison Latter endowed Chair; Ziering Family Foundation in memory of Sigi Ziering; Ben and Catherine Ivy Foundation; Art of the Brain Fund; Henry Singleton Brain Cancer Fund; Samuel Waxman Cancer Research Foundation; Uehara Memorial Foundation FX This work was supported by NIH grants CA119347 and NS73831 (P.S. Mischel), Accelerate Brain Cancer Cure (P.S. Mischel), STOP Cancer (P.S. Mischel), The Fred Miller Family (P.S. Mischel), The John W. Carson Foundation (P.S. Mischel), The Lya and Harrison Latter endowed Chair (P.S. Mischel), Ziering Family Foundation in memory of Sigi Ziering (T.F. Cloughesy and P.S. Mischel), The Ben and Catherine Ivy Foundation Fund (W.H. Yong and T.F. Cloughesy), Art of the Brain Fund (W.H. Yong and T.F. Cloughesy), Henry Singleton Brain Cancer Fund (W.H. Yong and T.F. Cloughesy), NIH grant P01-CA95616 (W.K. Cavenee), NIH grant CA122617 (B.D. Manning), NIH grants CA75080 and CA73756 (A.S. Baldwin), Samuel Waxman Cancer Research Foundation (A.S. Baldwin), and Uehara Memorial Foundation (K. Tanaka). NR 54 TC 111 Z9 115 U1 1 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD NOV PY 2011 VL 1 IS 6 BP 524 EP 538 DI 10.1158/2159-8290.CD-11-0124 PG 15 WC Oncology SC Oncology GA 880MR UT WOS:000299411700031 PM 22145100 ER PT J AU Beaser, RS Okeke, E Neighbours, J Brown, J Ronk, K Wolyniec, WW AF Beaser, Richard S. Okeke, Eyiuche Neighbours, James Brown, Julie Ronk, Katie Wolyniec, Walter W. TI COORDINATED PRIMARY AND SPECIALTY CARE FOR TYPE 2 DIABETES MELLITUS, GUIDELINES, AND SYSTEMS: AN EDUCATIONAL NEEDS ASSESSMENT SO ENDOCRINE PRACTICE LA English DT Article ID BLOOD-GLUCOSE CONTROL; COMPLICATIONS; MANAGEMENT; ASSOCIATION; PROGRESSION; THERAPY; ADULTS; RISK AB Objective: To determine knowledge, competence, and attitudinal issues among primary care providers (PCPs) and diabetes specialists regarding the use and application of evidence-based clinical guidelines and the coordination of care between PCPs and diabetes specialists specifically related to referral practices for patients with diabetes. Methods: A survey tool was completed by 491 PCPs and 249 diabetes specialists. Data were collected from specialists online and from PCP attendees at live symposia across the United States. Results were analyzed for frequency of response and evaluation of significant relationships among the variables. Results: Suboptimal practice patterns and interprofessional communication as well as gaps in diabetes-related knowledge and processes were identified. PCPs reported a lack of clarity about who, PCP or specialist, should assume clinical responsibility for the management of diabetes after a specialty referral. PCPs were most likely to refer patients to diabetes specialists for management issues relating to insulin therapy and use of advanced treatment strategies, such as insulin pens and continuous glucose monitoring. A minority of PCPs and even fewer specialists reported the routine use of clinical guidelines in practice. Conclusion: This research-based assessment identified critical educational needs and gaps related to coordinated care for patients with diabetes as well as the need for quality- and performance-based educational interventions. (Endocr Pract. 2011;17:880-890) C1 [Beaser, Richard S.; Okeke, Eyiuche; Neighbours, James; Brown, Julie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ronk, Katie] Forward Hlth Grp Inc, Madison, WI USA. [Wolyniec, Walter W.] Confluent Healthcare Solut Inc, Ridgefield, CT USA. RP Beaser, RS (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Richard.Beaser@joslin.harvard.edu FU Pfizer Inc. FX Funding for this research was provided in the form of an independent educational grant from Pfizer Inc. This research was conducted in collaboration with the American Association of Clinical Endocrinologists. NR 19 TC 9 Z9 9 U1 1 U2 2 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD NOV-DEC PY 2011 VL 17 IS 6 BP 880 EP 890 DI 10.4158/EP10398.OR PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 876YQ UT WOS:000299144100006 PM 21550953 ER PT J AU Kelly, M Conway, M Wirth, K Potter-Bynoe, G Billett, AL Sandora, TJ AF Kelly, Matthew Conway, Margaret Wirth, Kathleen Potter-Bynoe, Gail Billett, Amy L. Sandora, Thomas J. TI Moving CLABSI Prevention beyond the Intensive Care Unit: Risk Factors in Pediatric Oncology Patients SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID BLOOD-STREAM INFECTIONS; CRITICALLY-ILL PATIENTS; VENOUS ACCESS DEVICES; SURVEILLANCE; CHILDREN; TRANSFUSION; CANCER; METAANALYSIS; CATHETERS; MORTALITY AB BACKGROUND AND OBJECTIVE. Central line-associated bloodstream infections (CLABSIs) frequently complicate the use of central venous catheters (CVCs) among pediatric patients with cancer. Our objectives were to describe the microbiology and identify risk factors for hospital-onset CLABSI in this patient population. DESIGN. Retrospective case-control study. SETTING. Oncology and stem cell transplant units of a freestanding, 396-bed quaternary care pediatric hospital. PARTICIPANTS. Case subjects (N = 54) were patients with a diagnosis of malignancy and/or stem cell transplant recipients with CLABSI occurring during admission. Controls (N = 108) were identified using risk set sampling of hospitalizations among patients with a CVC, matched on date of admission. METHODS. Multivariate conditional logistic regression was used to identify independent predictors of CLABSI. RESULTS. The majority of CLABSI isolates were gram-positive bacteria (58%). The most frequently isolated organism was Enterococcus faecium, and 6 of 9 isolates were resistant to vancomycin. In multivariate analyses, independent risk factors for CLABSI included platelet transfusion within the prior week (odds ratio [OR], 10.90 [95% confidence interval (CI), 3.02-39.38]; P <.001) and CVC placement within the previous month (< 1 week vs >= 1 month: OR, 11.71 [95% CI, 1.98-69.20]; P = .02; >= 1 week and < 1 month vs >= 1 month: OR, 7.37 [95% CI, 1.85-29.36]; Pp. 004). CONCLUSIONS. Adjunctive measures to prevent CLABSI among pediatric oncology patients may be most beneficial in the month following CVC insertion and in patients requiring frequent platelet transfusions. Vancomycin-resistant enterococci may be an emerging cause of CLABSI in hospitalized pediatric oncology patients and are unlikely to be treated by typical empiric antimicrobial regimens. Infect Control Hosp Epidemiol 2011; 32(11): 1079-1085 C1 [Kelly, Matthew; Sandora, Thomas J.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Conway, Margaret] Childrens Hosp, Med Patient Serv, Boston, MA 02115 USA. [Wirth, Kathleen] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Billett, Amy L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Billett, Amy L.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Sandora, Thomas J.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Sandora, Thomas J.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. RP Kelly, M (reprint author), Childrens Hosp Philadelphia, Dept Global Hlth, 3535 Market St,13th Floor,Suite 1315, Philadelphia, PA 19104 USA. EM kellym8@email.chop.edu FU US National Institutes of Health [AI 007433] FX Financial support. K.W. received grant support from the US National Institutes of Health (AI 007433). NR 40 TC 17 Z9 17 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD NOV PY 2011 VL 32 IS 11 BP 1079 EP 1085 DI 10.1086/662376 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 876CB UT WOS:000299083500004 PM 22011534 ER PT J AU Venkatesh, AK Pallin, DJ Kayden, S Schuur, JD AF Venkatesh, Arjun K. Pallin, Daniel J. Kayden, Stephanie Schuur, Jeremiah D. TI Predictors of Hand Hygiene in the Emergency Department SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article AB We conducted an observational study to identify predictors of hand hygiene (HH) in the emergency department. Compliance with HH was 89.7% over 5,865 opportunities. Observation unit, hallway or high-visibility location, glove use, and worker type predicted worse HH. Hallway location was the strongest predictor (relative risk, 88.9% [95% confidence interval, 85.9%-92.1%]). Infect Control Hosp Epidemiol 2011; 32(11): 1120-1123 C1 [Pallin, Daniel J.; Kayden, Stephanie; Schuur, Jeremiah D.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Venkatesh, Arjun K.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. [Pallin, Daniel J.] Harvard Univ, Childrens Hosp, Sch Med, Div Emergency Med, Boston, MA 02115 USA. [Pallin, Daniel J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Schuur, JD (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St,Neville House,2nd Floor, Boston, MA 02115 USA. EM jschuur@partners.org RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 FU Department of Emergency Medicine at Brigham and Women's Hospital; Agency for Healthcare Research and Quality FX Financial support. This study was funded by the Department of Emergency Medicine at Brigham and Women's Hospital.; Potential conflicts of interest. A.K.V. is part holder of a provisional patent for a hand hygiene delivery device that had no relation to this study. J.D.S. received no direct support for this project; he receives grant funding from the Agency for Healthcare Research and Quality to identify and develop best practices to prevent healthcare-associated infections in emergency departments. D.J.P. and S.R. report no conflicts of interest relevant to this article. NR 10 TC 8 Z9 8 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD NOV PY 2011 VL 32 IS 11 BP 1120 EP 1123 DI 10.1086/662374 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 876CB UT WOS:000299083500011 PM 22011541 ER PT J AU Bryant, AS Cheng, YW Caughey, AB AF Bryant, Allison S. Cheng, Yvonne W. Caughey, Aaron B. TI Equality in Obstetrical Care: Racial/Ethnic Variation in Group B Streptococcus Screening SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE GBS screening; Disparities; Quality of care ID PRETERM BIRTH; UNITED-STATES; RISK-FACTORS; DISEASE; DISPARITIES; PREVENTION; COHORT AB The objective of this article is to determine whether racial/ethnic disparities exist in screening for group B streptococcus (GBS) colonization among pregnant women. A retrospective cohort study of deliveries at a single institution was conducted. The primary outcome was the availability of GBS culture data at the time of delivery; the primary predictor was maternal race/ethnicity. Analyses were stratified by the time periods before and after the CDC recommendations for universal screening for GBS. Among 16,333 deliveries, 60.4% of the population was screened for GBS but screening rates varied markedly by year of delivery. Black women had a lower odds of having available GBS data (AOR 0.81 [0.69, 0.95]) but this disparity was limited to the period of time before universal screening was recommended. Prior to the recommendation for universal screening for GBS, racial/ethnic disparities existed in rates of screening among pregnant women delivering at term. These differences were reduced after 2002, suggesting that uniform policies regarding obstetrical care may be effective in eliminating disparities in obstetrical care and outcomes. C1 [Bryant, Allison S.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Cheng, Yvonne W.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. [Caughey, Aaron B.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. RP Bryant, AS (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA. EM abryant@partners.org FU NIHJNCRR/CD UCSF-CTSI [KL2 RR024130]; Amos Medical Faculty Development Award of the Robert Wood Johnson Foundation [RWJF-63524]; Robert Wood Johnson Foundation as a Physician Faculty Scholar [RWJF-61535]; Women's Reproductive Health Research Scholar at the University of California, San Francisco FX This publication was supported by NIHJNCRR/CD UCSF-CTSI Grant No. KL2 RR024130 (Dr. Bryant). Its contents arc solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Dr. Bryant is also supported by the Amos Medical Faculty Development Award of the Robert Wood Johnson Foundation, Grant No. RWJF-63524. Dr. Caughey is supported by the Robert Wood Johnson Foundation as a Physician Faculty Scholar Grant No. RWJF-61535. Dr. Cheng is supported as a Women's Reproductive Health Research Scholar at the University of California, San Francisco. NR 21 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD NOV PY 2011 VL 15 IS 8 BP 1160 EP 1165 DI 10.1007/s10995-010-0682-8 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 875AK UT WOS:000299001000005 PM 20853139 ER PT J AU Kerry, VB Ndung'u, T Walensky, RP Lee, PT Kayanja, VFIB Bangsberg, DR AF Kerry, Vanessa B. Ndung'u, Thumbi Walensky, Rochelle P. Lee, Patrick T. Kayanja, V. Frederick I. B. Bangsberg, David R. TI Managing the Demand for Global Health Education SO PLOS MEDICINE LA English DT Editorial Material ID MEDICAL-EDUCATION; ACADEMIC-INSTITUTIONS; INTERNATIONAL HEALTH; TROPICAL MEDICINE; OPPORTUNITIES; CORPS; PROFESSIONALS; PROGRAMS; STUDENTS; SCHOOLS C1 [Kerry, Vanessa B.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Kerry, Vanessa B.; Walensky, Rochelle P.; Lee, Patrick T.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Kerry, Vanessa B.] Massachusetts Gen Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02114 USA. [Ndung'u, Thumbi] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Walensky, Rochelle P.; Lee, Patrick T.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Kayanja, V. Frederick I. B.; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. RP Kerry, VB (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. EM vkerry@partners.org RI yan, liu/A-1822-2015; OI yan, liu/0000-0001-8517-1084; Walensky, Rochelle P./0000-0002-8795-379X; Ndung'u, Thumbi/0000-0003-2962-3992 FU NIAID NIH HHS [P30 AI060354, R01 AI058736]; NIMH NIH HHS [K24 MH087227, K24 MH87227] NR 63 TC 24 Z9 24 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD NOV PY 2011 VL 8 IS 11 AR e1001118 DI 10.1371/journal.pmed.1001118 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 862ZR UT WOS:000298133100004 PM 22087076 ER PT J AU Kilpelainen, TO Qi, L Brage, S Sharp, SJ Sonestedt, E Demerath, E Ahmad, T Mora, S Kaakinen, M Sandholt, CH Holzapfel, C Autenrieth, CS Hypponen, E Cauchi, S He, MA Kutalik, Z Kumari, M Stancakova, A Meidtner, K Balkau, B Tan, JT Mangino, M Timpson, NJ Song, YQ Zillikens, MC Jablonski, KA Garcia, ME Johansson, S Bragg-Gresham, JL Wu, Y van Vliet-Ostaptchouk, JV Onland-Moret, NC Zimmermann, E Rivera, NV Tanaka, T Stringham, HM Silbernagel, G Kanoni, S Feitosa, MF Snitker, S Ruiz, JR Metter, J Larrad, MTM Atalay, M Hakanen, M Amin, N Cavalcanti-Proenca, C Grontved, A Hallmans, G Jansson, JO Kuusisto, J Kahonen, M Lutsey, PL Nolan, JJ Palla, L Pedersen, O Perusse, L Renstrom, F Scott, RA Shungin, D Sovio, U Tammelin, TH Ronnemaa, T Lakka, TA Uusitupa, M Rios, MS Ferrucci, L Bouchard, C Meirhaeghe, A Fu, M Walker, M Borecki, IB Dedoussis, GV Fritsche, A Ohlsson, C Boehnke, M Bandinelli, S van Duijn, CM Ebrahim, S Lawlor, DA Gudnason, V Harris, TB Sorensen, TIA Mohlke, KL Hofman, A Uitterlinden, AG Tuomilehto, J Lehtimaki, T Raitakari, O Isomaa, B Njolstad, PR Florez, JC Liu, SM Ness, A Spector, TD Tai, ES Froguel, P Boeing, H Laakso, M Marmot, M Bergmann, S Power, C Khaw, KT Chasman, D Ridker, P Hansen, T Monda, KL Illig, T Jarvelin, MR Wareham, NJ Hu, FB Groop, LC Orho-Melander, M Ekelund, U Franks, PW Loos, RJF AF Kilpelaeinen, Tuomas O. Qi, Lu Brage, Soren Sharp, Stephen J. Sonestedt, Emily Demerath, Ellen Ahmad, Tariq Mora, Samia Kaakinen, Marika Sandholt, Camilla Helene Holzapfel, Christina Autenrieth, Christine S. Hyppoenen, Elina Cauchi, Stephane He, Meian Kutalik, Zoltan Kumari, Meena Stancakova, Alena Meidtner, Karina Balkau, Beverley Tan, Jonathan T. Mangino, Massimo Timpson, Nicholas J. Song, Yiqing Zillikens, M. Carola Jablonski, Kathleen A. Garcia, Melissa E. Johansson, Stefan Bragg-Gresham, Jennifer L. Wu, Ying van Vliet-Ostaptchouk, Jana V. Onland-Moret, N. Charlotte Zimmermann, Esther Rivera, Natalia V. Tanaka, Toshiko Stringham, Heather M. Silbernagel, Guenther Kanoni, Stavroula Feitosa, Mary F. Snitker, Soren Ruiz, Jonatan R. Metter, Jeffery Martinez Larrad, Maria Teresa Atalay, Mustafa Hakanen, Maarit Amin, Najaf Cavalcanti-Proenca, Christine Grontved, Anders Hallmans, Goran Jansson, John-Olov Kuusisto, Johanna Kahonen, Mika Lutsey, Pamela L. Nolan, John J. Palla, Luigi Pedersen, Oluf Perusse, Louis Renstrom, Frida Scott, Robert A. Shungin, Dmitry Sovio, Ulla Tammelin, Tuija H. Ronnemaa, Tapani Lakka, Timo A. Uusitupa, Matti Serrano Rios, Manuel Ferrucci, Luigi Bouchard, Claude Meirhaeghe, Aline Fu, Mao Walker, Mark Borecki, Ingrid B. Dedoussis, George V. Fritsche, Andreas Ohlsson, Claes Boehnke, Michael Bandinelli, Stefania van Duijn, Cornelia M. Ebrahim, Shah Lawlor, Debbie A. Gudnason, Vilmundur Harris, Tamara B. Sorensen, Thorkild I. A. Mohlke, Karen L. Hofman, Albert Uitterlinden, Andre G. Tuomilehto, Jaakko Lehtimaki, Terho Raitakari, Olli Isomaa, Bo Njolstad, Pal R. Florez, Jose C. Liu, Simin Ness, Andy Spector, Timothy D. Tai, E. Shyong Froguel, Philippe Boeing, Heiner Laakso, Markku Marmot, Michael Bergmann, Sven Power, Chris Khaw, Kay-Tee Chasman, Daniel Ridker, Paul Hansen, Torben Monda, Keri L. Illig, Thomas Jarvelin, Marjo-Riitta Wareham, Nicholas J. Hu, Frank B. Groop, Leif C. Orho-Melander, Marju Ekelund, Ulf Franks, Paul W. Loos, Ruth J. F. TI Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children SO PLOS MEDICINE LA English DT Article ID BODY-MASS INDEX; UNITED-STATES; ENVIRONMENT INTERACTION; RS9939609 POLYMORPHISM; DIABETES PREVENTION; WAIST CIRCUMFERENCE; GENETIC-VARIANTS; IDENTICAL-TWINS; COMMON VARIANT; WEIGHT-LOSS AB Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n=218,166) and nine studies of children and adolescents (n=19,268). Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTOxPA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. Conclusions: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity. C1 [Kilpelaeinen, Tuomas O.; Brage, Soren; Sharp, Stephen J.; Palla, Luigi; Scott, Robert A.; Wareham, Nicholas J.; Ekelund, Ulf; Loos, Ruth J. F.] Inst Metab Sci, Med Res Council Epidemiol Unit, Cambridge, England. [Qi, Lu; Renstrom, Frida; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Qi, Lu; Renstrom, Frida; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Sonestedt, Emily; Renstrom, Frida; Shungin, Dmitry; Groop, Leif C.; Orho-Melander, Marju; Franks, Paul W.] Lund Univ, Skane Univ Hosp, Dept Clin Sci, Lund Univ Diabet Ctr, Malmo, Sweden. [Demerath, Ellen; Lutsey, Pamela L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Ahmad, Tariq] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. [Kaakinen, Marika; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Kaakinen, Marika; Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Sandholt, Camilla Helene; Pedersen, Oluf; Hansen, Torben] Hagedorn Res Inst, Gentofte, Denmark. [Holzapfel, Christina; Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Unit Mol Epidemiol, Neuherberg, Germany. [Holzapfel, Christina] Tech Univ Munich, Klinikum Rechts Isar, Univ Hosp, Else Kroener Fresenius Ctr Nutr Med, D-8000 Munich, Germany. [Autenrieth, Christine S.] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Hyppoenen, Elina; Power, Chris] UCL, Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England. [Hyppoenen, Elina; Power, Chris] UCL, Inst Child Hlth, MRC, Ctr Epidemiol Child Hlth, London, England. [Cauchi, Stephane; Cavalcanti-Proenca, Christine; Froguel, Philippe] Inst Biol Lille, Dept Genom & Mol Physiol Metab Dis, CNRS UMR 8090, Lille, France. [Kutalik, Zoltan; Bergmann, Sven] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. [Kumari, Meena] UCL, Dept Epidemiol, Genet Epidemiol Grp, London, England. [Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Meidtner, Karina; Boeing, Heiner] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, Nuthetal, Germany. [Balkau, Beverley] INSERM, CESP Ctr Res Epidemiol & Populat Hlth, U1018, Villejuif, France. [Balkau, Beverley] Univ Paris 11, UMRS 1018, Villejuif, France. [Tan, Jonathan T.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Epidemiol & Publ Hlth, Singapore 117595, Singapore. [Mangino, Massimo; Spector, Timothy D.] Kings Coll London, London WC2R 2LS, England. [Timpson, Nicholas J.; Lawlor, Debbie A.] Univ Bristol, Sch Social & Community Med, Ctr Causal Anal Translat Epidemiol, MRC, Bristol, Avon, England. [Song, Yiqing] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. [Zillikens, M. Carola; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Zillikens, M. Carola; van Duijn, Cornelia M.; Hofman, Albert; Uitterlinden, Andre G.] Netherlands Consortium Hlth Aging, Netherlands Genom Initiat, Leiden, Netherlands. [Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Johansson, Stefan] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway. [Johansson, Stefan; Njolstad, Pal R.] Univ Bergen, Dept Clin Med, Bergen, Norway. [Bragg-Gresham, Jennifer L.; Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Bragg-Gresham, Jennifer L.; Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Wu, Ying; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [van Vliet-Ostaptchouk, Jana V.] Univ Med Ctr Groningen, Dept Pathol & Med Biol, Mol Genet Sect, NL-9713 AV Groningen, Netherlands. [van Vliet-Ostaptchouk, Jana V.] Univ Groningen, Groningen, Netherlands. [Onland-Moret, N. Charlotte] Univ Med Ctr Utrecht, Dept Med Genet, Complex Genet Sect, Utrecht, Netherlands. [Onland-Moret, N. Charlotte] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Zimmermann, Esther; Sorensen, Thorkild I. A.] Copenhagen Univ Hosp, Inst Prevent Med, Copenhagen, Denmark. [Zimmermann, Esther; Pedersen, Oluf] Univ Copenhagen, Fac Hlth Sci, Inst Biomed Sci, Copenhagen, Denmark. [Rivera, Natalia V.; Amin, Najaf; van Duijn, Cornelia M.; Hofman, Albert; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands. [Tanaka, Toshiko] Medstar Res Inst, Baltimore, MD USA. [Tanaka, Toshiko; Metter, Jeffery; Ferrucci, Luigi] NIA, Longitudinal Study Sect, NIH, Baltimore, MD 21224 USA. [Silbernagel, Guenther; Fritsche, Andreas] Univ Tubingen, Dept Internal Med, Div Endocrinol Diabetol Nephrol Vasc Dis & Clin C, D-7400 Tubingen, Germany. [Kanoni, Stavroula; Dedoussis, George V.] Harokopio Univ Athens, Dept Nutr Dietet, Athens, Greece. [Feitosa, Mary F.; Borecki, Ingrid B.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA. [Snitker, Soren] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Ruiz, Jonatan R.] Karolinska Inst, Novum, Dept Biosci & Nutr, Unit Prevent Nutr, Huddinge, Sweden. [Ruiz, Jonatan R.] Univ Granada, Sch Phys Act & Sport Sci, Dept Phys Educ & Sport, Granada, Spain. [Martinez Larrad, Maria Teresa; Serrano Rios, Manuel] Hosp Clin San Carlos, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain. [Atalay, Mustafa; Lakka, Timo A.] Univ Eastern Finland, Dept Physiol, Inst Biomed, Kuopio, Finland. [Hakanen, Maarit; Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Grontved, Anders] Univ So Denmark, Inst Sport Sci & Clin Biomech, Odense, Denmark. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Sect Nutr Res, Umea, Sweden. [Jansson, John-Olov] Univ Gothenburg, Sahlgrenska Acad, Dept Physiol, Inst Neurosci & Physiol, Gothenburg, Sweden. [Nolan, John J.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Kahonen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Kahonen, Mika; Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland. [Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark. [Pedersen, Oluf; Hansen, Torben] Univ Copenhagen, Fac Hlth Sci, Marie Krogh Ctr Metab Res, Copenhagen, Denmark. [Perusse, Louis] Univ Laval, Dept Social & Prevent Med, Div Kinesiol, Ste Foy, PQ, Canada. [Renstrom, Frida; Shungin, Dmitry; Franks, Paul W.] Umea Univ Hosp, Med Sect, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden. [Shungin, Dmitry] Umea Univ, Dept Odontol, Umea, Sweden. [Sovio, Ulla] London Sch Hyg & Trop Med, Dept Med Stat, London WC1, England. [Tammelin, Tuija H.] Finnish Inst Occupat Hlth, Oulu, Finland. [Tammelin, Tuija H.] LIKES Res Ctr Sport & Hlth Sci, Jyvaskyla, Finland. [Ronnemaa, Tapani] Univ Turku, Dept Med, Turku, Finland. [Uusitupa, Matti] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland. [Uusitupa, Matti] Kuopio Univ Hosp, Res Unit, SF-70210 Kuopio, Finland. [Bouchard, Claude] Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA USA. [Meirhaeghe, Aline] Univ Lille 2, Univ Lille Nord France, Inst Pasteur Lille, INSERM,U744, Lille, France. [Fu, Mao] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Walker, Mark] Newcastle Univ, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Ohlsson, Claes] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res,Dept Internal Med, Gothenburg, Sweden. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil Unit, Florence, Italy. [van Duijn, Cornelia M.] Netherlands Genom Initiat, Ctr Med Syst Biol, Leiden, Netherlands. [Ebrahim, Shah] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1, England. [Gudnason, Vilmundur] Iceland Heart Assoc, Heart Prevent Clin, Kopavogur, Iceland. [Gudnason, Vilmundur] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland. [Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Harris, Tamara B.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland. [Tuomilehto, Jaakko] Danube Univ Krems, Dept Clin & Prevent Med, Krems, Austria. [Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland. [Isomaa, Bo] Folkhalsan Res Ctr, Helsinki, Finland. [Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland. [Njolstad, Pal R.] Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. [Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Liu, Simin] Univ Calif Los Angeles, Sch Publ Hlth, Ctr Metab Dis Prevent, Los Angeles, CA 90024 USA. [Liu, Simin] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Ness, Andy] Univ Bristol, Sch Oral & Dent Sci, Bristol, Avon, England. [Tai, E. Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Ctr Genom Med, London, England. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Genom Med, London, England. [Marmot, Michael] UCL, Dept Epidemiol & Publ Hlth, London, England. [Khaw, Kay-Tee] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England. [Hansen, Torben] Univ So Denmark, Fac Hlth Sci, Odense, Denmark. [Monda, Keri L.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England. [Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Life Course & Serv, Oulu, Finland. RP Kilpelainen, TO (reprint author), Inst Metab Sci, Med Res Council Epidemiol Unit, Cambridge, England. EM luqi@hsph.harvard.edu; paul.franks@med.lu.se; ruth.loos@mrc-epid.cam.ac.uk RI Sonestedt, Emily/I-3814-2016; Bouchard, Claude/A-7637-2009; mangino, massimo/F-5134-2011; Fox, Laura /C-6249-2016; Palla, Luigi/Q-4950-2016; Rivera, Natalia V/S-4231-2016; Feitosa, Mary/K-8044-2012; Onland-Moret, N. Charlotte/G-9185-2011; Gudnason, Vilmundur/K-6885-2015; RUIZ, JONATAN/M-1338-2015; Kilpelainen, Tuomas/F-8569-2012; Brage, Soren/C-6415-2013; Perusse, Louis/A-3444-2012; Hypponen, Elina/B-2596-2014; Liu, Simin/I-3689-2014; Berryman, Katie/J-4236-2014; Meirhaeghe, Aline/E-4663-2015; Johansson, Stefan/C-4394-2011; Colaus, PsyColaus/K-6607-2013 OI van Vliet-Ostaptchouk, Jana/0000-0002-7943-3153; Lakka, Timo/0000-0002-9199-2871; Grontved, Anders/0000-0003-1584-679X; Kumari, Meena/0000-0001-9716-1035; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Marmot, Michael/0000-0002-2431-6419; Lawlor, Debbie A/0000-0002-6793-2262; Tai, E Shyong/0000-0003-2929-8966; Sonestedt, Emily/0000-0002-0747-4562; mangino, massimo/0000-0002-2167-7470; Palla, Luigi/0000-0001-6944-1750; Rivera, Natalia V/0000-0002-1298-1243; Feitosa, Mary/0000-0002-0933-2410; Zimmermann, Esther/0000-0001-5854-0542; Kaakinen, Marika/0000-0002-9228-0462; Shungin, Dmitry/0000-0001-7900-5856; Meidtner, Karina/0000-0001-5810-4062; Gudnason, Vilmundur/0000-0001-5696-0084; RUIZ, JONATAN/0000-0002-7548-7138; Brage, Soren/0000-0002-1265-7355; Hypponen, Elina/0000-0003-3670-9399; Liu, Simin/0000-0003-2098-3844; Johansson, Stefan/0000-0002-2298-7008; FU British Heart Foundation [RG/07/008/23674]; Cancer Research UK [14136]; Department of Health [PHCS/C4/4/016]; Medical Research Council [G9815508, G0000934, G0100222, G0401527, G0601653, G0701863, G0902037, G1000143, G19/35, G8802774, MC_U106179471, MC_U106179473, MC_U106188470]; NIDDK NIH HHS [P30 DK017047, P30 DK072488, P30 DK079637, R01 DK072041, R01 DK072193, R01 DK078150, R01 DK091718]; Wellcome Trust [092731] NR 39 TC 168 Z9 173 U1 1 U2 76 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 NOV PY 2011 VL 8 IS 11 AR e1001116 DI 10.1371/journal.pmed.1001116 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 862ZR UT WOS:000298133100003 PM 22069379 ER PT J AU Horwitz, R AF Horwitz, Russell TI Rising From the Rubble: Perspectives of an American Expatriate in Haiti SO ACADEMIC PSYCHIATRY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Horwitz, R (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM rhorwitz@partners.org NR 15 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD NOV-DEC PY 2011 VL 35 IS 6 BP 397 EP 399 PG 3 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 861ZT UT WOS:000298060300015 PM 22193739 ER PT J AU Morse, MD Raviola, G Fricchione, G Berger, E AF Morse, Michael Dorian Raviola, Giuseppe Fricchione, Gregory Berger, Elizabeth TI Telesupervision for Medical Student Rotations in Global Health Psychiatry SO ACADEMIC PSYCHIATRY LA English DT Letter C1 [Morse, Michael Dorian; Berger, Elizabeth] George Washington Univ, Dept Psychiat, Washington, DC 20052 USA. [Raviola, Giuseppe] Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Fricchione, Gregory] Mass Gen Hosp, Dept Psychiat, Boston, MA USA. RP Morse, MD (reprint author), George Washington Univ, Dept Psychiat, Washington, DC 20052 USA. EM michael_morse@hms.harvard.edu NR 6 TC 4 Z9 4 U1 1 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD NOV-DEC PY 2011 VL 35 IS 6 BP 415 EP 416 PG 2 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 861ZT UT WOS:000298060300020 PM 22193744 ER PT J AU Banerji, A AF Banerji, Aleena TI Hereditary angioedema: Classification, pathogenesis, and diagnosis SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article ID INTERNATIONAL CONSENSUS ALGORITHM; C1 INHIBITOR DEFICIENCY; ANGIONEUROTIC-EDEMA; LABORATORY DIAGNOSIS; HELICOBACTER-PYLORI; FACTOR-XII; MANAGEMENT; THERAPY; PATHOPHYSIOLOGY; MUTATIONS AB Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder associated with a deficiency in Cl inhibitor. More than 200 mutations in this gene, located on chromosome 11, have been identified. Although HAE is often inherited, 20-25% of cases are from new spontaneous mutations and they have no family history of swelling. Decreased Cl inhibitor activity leads to inappropriate activation of multiple pathways, including the complement and contact systems and the fibrinolysis and coagulation systems. Reduced Cl inhibitor activity results in increased activation of plasma kallikrein-kinin system proteases and increased bradykinin levels. Bradykinin is felt to be the main mediator of symptoms in HAE. Patients with HAE have recurrent episodes of swelling of the extremities, abdomen, face, and upper airway. Angioedema involving the gastrointestinal tract can lead to intestinal wall edema, which results in abdominal pain, nausea, vomiting, and diarrhea. Laryngeal swelling is life-threatening and may lead to asphyxia. Common triggers of an attack include trauma, stress, infection, menstruation, oral contraceptives, hormone replacement therapy, and angiotensin-converting enzyme inhibitors. Laboratory testing including C4, C1 inhibitor level, and function is needed to confirm or rule out the diagnosis of HAE. The treatment of HAE has improved significantly in recent years with the availability of several safe and effective therapies. Several consensus guidelines have been created to further assist in the management of HAE patients. This review will provide an update on the classification, pathophysiology, clinical presentation, and diagnosis of HAE. (Allergy Asthma Proc 32:403-407, 2011; doi: 10.2500/aap.2011.32.3492) C1 [Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. RP Banerji, A (reprint author), Cox 201,55 Fruit St, Boston, MA 02114 USA. EM abanerji@partners.org FU Dyax; Shire; ViroPharma FX Supported by an educational grant from Dyax, Shire and ViroPharma A Banerji is a consultant and advisory board member for Oyax, and Shire NR 39 TC 14 Z9 14 U1 1 U2 3 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD NOV-DEC PY 2011 VL 32 IS 6 BP 403 EP 407 DI 10.2500/aap.2011.32.3492 PG 5 WC Allergy SC Allergy GA 874FR UT WOS:000298941300001 PM 22221432 ER PT J AU Kofonow, JM Bhuskute, A Doghramji, L Palmer, JN Cohen, NA Chiu, AG AF Kofonow, Jennifer M. Bhuskute, Aditi Doghramji, Laurel Palmer, James N. Cohen, Noam A. Chiu, Alexander G. TI One-way valve bottle contamination rates in the immediate post-functional endoscopic sinus surgery period SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID RHINOSINUSITIS PATIENTS AB Background: Sinonasal saline irrigation has become an accepted practice in the immediate postoperative management of functional endoscopic sinus surgery (FESS) patients. Recent studies have found that valveless delivery systems of sinonasal irrigation are colonized with bacteria. An alternative delivery system uses a one-way valve to reduce saline backflow and may limit bottle contamination. Our sole objective was to determine whether this system in post-FESS patients eliminates microbial bottle contamination. Methods: Eight patients undergoing FESS were given one-way valve irrigation bottles to use immediately after surgery. Bottles were collected after 1 week of use and another set of bottles after an additional week. Endoscopic-directed cultures of the middle meatus were performed at the time of surgery. Returned used bottles were swabbed for bacteria and the valve system of the bottle was analyzed under scanning electron microscopy (SEM) for the presence of bacteria. Results: All sinus swabs collected at the time of surgery grew bacteria with Staphylococcus sp. present in all samples. After the 1st week of use, 5/8 bottles grew bacterial cultures and showed bacterial presence on the valves by SEM. After the 2nd week, 4/5 bottles had positive culture results and also showed bacterial presence on the valves by SEM. Conclusion: Despite commercial claims that the use of valves and limit of backflow into the bottle will eliminate contamination, our study showed that one-way valve delivery systems become contaminated with bacteria after 1 week of use. We also showed that the bottle valves themselves harbor bacteria after 1 week of use. (Am J Rhinol Allergy 25, 393-396, 2011; doi:10.2500/ajra.2011.25.3664) C1 [Kofonow, Jennifer M.; Doghramji, Laurel; Palmer, James N.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol, Philadelphia, PA 19104 USA. [Bhuskute, Aditi; Chiu, Alexander G.] Univ Arizona, Dept Surg, Tucson, AZ USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Cohen, NA (reprint author), Univ Penn, Dept Otorhinolaryngol, Ravdin Bldg 5th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM Noam.Cohen@uphs.upenn.edu RI Chiu, Alexander/J-1230-2014; OI Chiu, Alexander/0000-0002-7592-6575; Cohen, Noam/0000-0002-9462-3932 FU NeilMed Pharmaceuticals, Inc. FX J.N. Palmer, N.A. Cohen and A.G. Chiu have in the past received royalties from NeilMed Pharmaceuticals, Inc. The remaining authors have nothing to declare pertaining to this article NR 11 TC 2 Z9 2 U1 0 U2 5 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 NOV-DEC PY 2011 VL 25 IS 6 BP 393 EP 396 DI 10.2500/ajra.2011.25.3664 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 868RT UT WOS:000298543100019 PM 22185742 ER PT J AU Kastrinos, F Syngal, S AF Kastrinos, Fay Syngal, Sapna TI Inherited Colorectal Cancer Syndromes SO CANCER JOURNAL LA English DT Review DE Inherited colorectal cancer syndromes ID FAMILIAL ADENOMATOUS POLYPOSIS; MSH6 GERMLINE MUTATIONS; REPAIR-GENE-MUTATIONS; LYNCH-SYNDROME; COLON-CANCER; MICROSATELLITE INSTABILITY; DUODENAL ADENOMATOSIS; CLINICAL-IMPLICATIONS; MYH MUTATIONS; RISK AB Colorectal cancer is the most common gastrointestinal malignancy and the second leading cause of cancer death in both men and women in the United States. Most colorectal cancer cases diagnosed annually are due to sporadic events, but up to 5% are attributed to known monogenic disorders including Lynch syndrome, familial adenomatous polyposis, MYH-associated polyposis, and the rare hamartomatous polyposis syndromes. These inherited colorectal cancer syndromes confer a markedly increased risk for the development of multiple cancers, and predictive genetic testing is available to identify mutation carriers and at-risk family members. Through personalized strategies for diagnosis and management, a substantial reduction in morbidity and mortality has been appreciated among patients at highest risk for the development of colorectal cancer. C1 [Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Kastrinos, Fay] Columbia Univ Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Kastrinos, Fay] Columbia Univ Med Ctr, Div Digest & Liver Dis, New York, NY USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 1 Jimmy Fund Way,SM 209, Boston, MA 02115 USA. EM ssyngal@partners.org FU National Cancer Institute [K24 113433, K07 151769] FX K24 113433 to Dr Syngal and K07 151769 to Dr Kastrinos from the National Cancer Institute. NR 71 TC 21 Z9 24 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD NOV-DEC PY 2011 VL 17 IS 6 SI SI BP 405 EP 415 DI 10.1097/PPO.0b013e318237e408 PG 11 WC Oncology SC Oncology GA 863HH UT WOS:000298152900002 PM 22157284 ER PT J AU Pomerantz, MM Freedman, ML AF Pomerantz, Mark M. Freedman, Matthew L. TI The Genetics of Cancer Risk SO CANCER JOURNAL LA English DT Review DE Inherited cancer risk; genetics; cancer biology; prostate cancer; patient management; genotype; phenotype; trait-associated alleles ID GENOME-WIDE ASSOCIATION; HEREDITARY PROSTATE-CANCER; SINGLE-NUCLEOTIDE POLYMORPHISM; LONG-RANGE INTERACTION; FAMILY-HISTORY; SUSCEPTIBILITY LOCI; BREAST-CANCER; COLORECTAL-CANCER; CHROMOSOME 8Q24; BLADDER-CANCER AB One hundred years ago, decades before the discovery of the structure of DNA, debate raged regarding how human traits were passed from one generation to the next. Phenotypes, including risk of disease, had long been recognized as having a familial component. Yet it was difficult to reconcile genetic segregation as described by Mendel with observations exhaustively documented by Karl Pearson and others regarding the normal distribution of human characteristics. In 1918, R. A. Fisher published his landmark article, "The Correlation Between Relatives on the Supposition of Mendelian Inheritance," bridging this divide and demonstrating that multiple alleles, all individually obeying Mendel's laws, account for the phenotypic variation observed in nature. Since that time, geneticists have sought to identify the link between genotype and phenotype. Trait-associated alleles vary in their frequency and degree of penetrance. Some minor alleles may approach a frequency of 50% in the human population, whereas others are present within only a few individuals. The spectrum for penetrance is similarly wide. These characteristics jointly determine the segregation pattern of a given trait, which, in turn, determine the method used to map the trait. Until recently, identification of rare, highly penetrant alleles was most practical. Revolutionary studies in genomics reported over the past decade have made interrogation of most of the spectrum of genetic variation feasible. The following article reviews recent discoveries in the genetic basis of inherited cancer risk and how these discoveries inform cancer biology and patient management. Although this article focuses on prostate cancer, the principles are generic for any cancer and, indeed, for any trait. C1 [Pomerantz, Mark M.; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Freedman, ML (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM freedman@broadinstitute.org FU NCI NIH HHS [R01 CA129435] NR 115 TC 9 Z9 9 U1 2 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD NOV-DEC PY 2011 VL 17 IS 6 SI SI BP 416 EP 422 DI 10.1097/PPO.0b013e31823e5387 PG 7 WC Oncology SC Oncology GA 863HH UT WOS:000298152900003 PM 22157285 ER PT J AU Martin, NE Mucci, LA Loda, M DePinho, RA AF Martin, Neil E. Mucci, Lorelei A. Loda, Massimo DePinho, Ronald A. TI Prognostic Determinants in Prostate Cancer SO CANCER JOURNAL LA English DT Review DE Prognosis; prostate; gene expression signatures; immunohistochemistry ID CIRCULATING TUMOR-CELLS; TMPRSS2-ERG FUSION TRANSCRIPTS; HUMAN GLANDULAR KALLIKREIN-2; BEAM RADIATION-THERAPY; FATTY-ACID SYNTHASE; RADICAL PROSTATECTOMY; GLEASON SCORE; FREE SURVIVAL; DISEASE RECURRENCE; PROTEIN EXPRESSION AB Clinical outcomes in prostate cancer are heterogeneous, and given the high prevalence of the disease, there is a pressing need to identify clinically useful markers of prognosis. Many clinical, pathological, molecular, and genetic factors have been investigated in this capacity, although relatively few are routinely used. With a growing understanding of the molecular pathogenesis of prostate cancer, there is the potential that the next generation of makers will prove sufficiently robust to guide the optimal management of men with prostate cancer. Here, we review the various clinical and molecular prognostic determinants in prostate cancer. C1 [DePinho, Ronald A.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Martin, Neil E.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM ron_depinho@dfci.harvard.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 FU Metamark Genetics FX Dr DePinho is the co-founder of Metamark Genetics, Dr Loda is a scientific advisor for Metamark Genetics, and Drs Mucci and Martin receive research support from Metamark Genetics. NR 116 TC 20 Z9 21 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD NOV-DEC PY 2011 VL 17 IS 6 SI SI BP 429 EP 437 DI 10.1097/PPO.0b013e31823b042c PG 9 WC Oncology SC Oncology GA 863HH UT WOS:000298152900005 PM 22157287 ER PT J AU Flaherty, KT AF Flaherty, Keith T. TI BRAF Inhibitors and Melanoma SO CANCER JOURNAL LA English DT Review DE BRAF; melanoma; oncogene; vemurafenib; dabrafenib ID B-RAF; MALIGNANT-MELANOMA; METASTATIC MELANOMA; ONCOGENIC BRAF(V600E); CELL-LINES; MUTATIONS; RESISTANCE; PATHWAY; KINASE; GROWTH AB Selective BRAF inhibitors have recently emerged as a new standard treatment for patients with metastatic melanoma harboring activating BRAF mutations. Inhibition of the MAP kinase pathway and initial evidence of antitumor effects are very reliably observed. However, many patients experience short-lived responses, whereas others are durable. An overall survival benefit has been established for them, BRAF in it, the agents that have advanced furthest in clinical development. Nonetheless, attention has immediately turned to understanding de novo and acquired resistance and effort to develop rational combination therapy that will further improve patient outcomes. Opportunities for combining BRAF inhibitors with other signal transduction inhibitors as well as targeted therapies with distinct mechanisms of action are discussed. C1 [Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Flaherty, KT (reprint author), 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM kflaherty@partners.org NR 69 TC 18 Z9 18 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD NOV-DEC PY 2011 VL 17 IS 6 SI SI BP 505 EP 511 DI 10.1097/PPO.0b013e31823e5357 PG 7 WC Oncology SC Oncology GA 863HH UT WOS:000298152900013 PM 22157295 ER PT J AU Peacock, ZS Chapman, PH Gupta, R Kaban, LB AF Peacock, Z. S. Chapman, P. H. Gupta, R. Kaban, L. B. TI Replication of ancient Egyptian osteotomies of the facial skeleton: insights into the mummification process SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article DE Egyptian mummy; coronoidectomy; mandibular hypomobility; muscles of mastication ID ANKYLOSIS; FRACTURE; HEAD AB A recent radiographic study of an Egyptian mummified head from the Middle Kingdom revealed methodical mutilations of the facial skeleton that were performed after death and prior to wrapping the corpse for burial. These mutilations consisted of removal of the coronoid processes of the mandible and portions of the zygomas presumably via an intraoral approach. They are unique in the archaeological record. The authors hypothesize that the procedures were carried out to facilitate jaw opening and may be related to a ritual known as the 'Opening of the Mouth' ceremony. The purpose of this study was to demonstrate the feasibility of performing these remarkable osteotomies on two human cadavers using instruments similar to those available to the ancient embalmer. Bilateral osteotomies of the zygomas and coronoid processes were carried out transorally and the bones removed. Pre- and postoperative maximal incisal opening measured 25 mm and 53 mm, respectively. Postoperative high-resolution computed tomographic (CT) scans were obtained. Comparison of the postoperative cadaver and mummy CT scans demonstrate remarkable similarity between the resections. Results of this study demonstrate that the ancient skeletal mutilations could have been performed transorally during the mummification process and would have enhanced jaw opening. C1 [Peacock, Z. S.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Neurosurg & Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Peacock, ZS (reprint author), Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Warren 1201,55 Fruit St, Boston, MA 02115 USA. EM zpeacock@partners.org FU Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital FX Education and Research Fund, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital. NR 21 TC 3 Z9 3 U1 2 U2 9 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD NOV PY 2011 VL 40 IS 11 BP 1301 EP 1306 DI 10.1016/j.ijom.2011.05.017 PG 6 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 871GV UT WOS:000298726800012 PM 21723092 ER PT J AU Teitelman, AM Stringer, M Nguyen, GT Hanlon, AL Averbuch, T Stimpfel, AW AF Teitelman, Anne M. Stringer, Marilyn Nguyen, Giang T. Hanlon, Alexandra L. Averbuch, Tali Stimpfel, Amy Witkoski TI Social Cognitive and Clinical Factors Associated with HPV Vaccine Initiation Among Urban, Economically Disadvantaged Women SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article DE HPV vaccine; theory of planned behavior; sexual health; adolescent; women's health; cervical cancer; prevention ID HUMAN-PAPILLOMAVIRUS VACCINATION; PLANNED BEHAVIOR; REASONED ACTION; UNITED-STATES; CERVICAL-CANCER; ACCEPTABILITY; ACCEPTANCE; INFECTION; DAUGHTERS; KNOWLEDGE AB Objective: To learn more about human papilloma virus (HPV) knowledge and vaccination among teens and young women age 13 to 26 years from an economically disadvantaged, urban community. Our aim was to identify common beliefs about HPV vaccine initiation and describe the relationship between attitudes, norms, perceived control, and intention to receive HPV vaccine, drawing from the theory of planned behavior (TPB). Design: Mixed method, descriptive design. Guided by the TPB, HPV vaccine beliefs were assessed through focus groups. Intention to receive the vaccine, demographic and clinical factors, and theoretical predictor variables (attitudes, norms, and control) were assessed through questionnaires. Setting: After recruitment, focus groups were held at a convenient date and time for our participants in a small university conference room. Participants: Participants were economically disadvantaged young women, age 13 to 26 (N = 34). Methods: Specific behavioral, normative, and control beliefs were elicited in focus groups and analyzed using content analysis. Simple and multivariate general linear modeling with adjustment for prognostic demographic and clinical factors was completed to assess the influence of the theoretical predictor variables on the outcome of HPV vaccine initiation. Results: Influential beliefs toward vaccination were identified. Analysis indicated attitudes, norms, and perceived control toward HPV vaccine initiation were highly significant predictors of intent, as was tobacco use; all p's < .001. Conclusion: Barriers to HPV vaccine initiation were identified, and strong preliminary evidence supports use of the TPB to guide programs to promote urban, economically disadvantaged young women's intent to begin the HPV vaccine. JOGNN, 40, 691-701; 2011. DOI: 10.1111/j.1552-6909.2011.01297.x C1 [Teitelman, Anne M.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19194 USA. [Nguyen, Giang T.] Univ Penn, Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19194 USA. [Averbuch, Tali] Univ Penn, Sch Nursing, Womens Hlth Nurse Practitioner Program, Philadelphia, PA 19194 USA. [Averbuch, Tali] Univ Penn, Sch Nursing, Nurse Midwifery Program, Philadelphia, PA 19194 USA. RP Teitelman, AM (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Fagin Hall 2L,Rm 244,418 Curie Blvd, Philadelphia, PA 19194 USA. EM teitelm@nursing.upenn.edu OI Nguyen, Giang/0000-0003-2031-9943 FU University of Pennsylvania School of Nursing; American Cancer Society [CCCDA-05-161-01] FX Supported by University of Pennsylvania School of Nursing Investing in the Future Grant. Dr. Nguyen was supported by a Cancer Control Career Development Award from the American Cancer Society (CCCDA-05-161-01) and a Pfizer Fellowship in Health Literacy/Clear Health Communication. NR 49 TC 9 Z9 9 U1 2 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-2175 J9 JOGNN-J OBST GYN NEO JI JOGNN PD NOV-DEC PY 2011 VL 40 IS 6 BP 691 EP 701 DI 10.1111/j.1552-6909.2011.01297.x PG 11 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 855OY UT WOS:000297575300005 PM 22092373 ER PT J AU Cappiello, J Beal, MW Gallogly-Hudson, K AF Cappiello, Joyce Beal, Margaret W. Gallogly-Hudson, Kim TI Applying Ethical Practice Competencies to the Prevention and Management of Unintended Pregnancy SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article DE Unintended pregnancy; ethical competencies; professional right of conscience; social justice ID SOCIAL-JUSTICE; REPRODUCTIVE HEALTH; CHILDBEARING WOMEN; UNITED-STATES; CARE; DISPARITIES; CONSCIENCE; OPTIONS; ISSUES; ACCESS AB Using a case study that incorporates patient, nurse practitioner, and student perspectives, we address ethical principles of respect for autonomy, beneficence, and fairness; professionals' right of conscience; and a social justice model for the discussion of prevention and management of unintended pregnancy. Through an ongoing process of self-reflection and values clarification, nurses can prepare for the challenge of applying ethical principles to the reproductive health care of women. JOGNN, 40, 808-816; 2011. DOI: 10.1111/j.1552-6909.2011.01307.x C1 [Cappiello, Joyce] Abort Access Project, Reprod Opt Educ Consortium, Cambridge, MA USA. [Beal, Margaret W.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Gallogly-Hudson, Kim] N Georgia Coll & State Univ, Dept Nursing, Dahlonega, GA USA. RP Cappiello, J (reprint author), Univ New Hampshire, Dept Nursing, Hewitt Hall,4 Lib Way, Durham, NH 03824 USA. EM joycec@unh.edu NR 45 TC 2 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-2175 J9 JOGNN-J OBST GYN NEO JI JOGNN PD NOV-DEC PY 2011 VL 40 IS 6 BP 808 EP 816 DI 10.1111/j.1552-6909.2011.01307.x PG 9 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 855OY UT WOS:000297575300017 PM 22273453 ER PT J AU Villiger, M Soroka, A Tearney, GJ Bouma, BE Vakoc, BJ AF Villiger, Martin Soroka, Andrew Tearney, Guillermo J. Bouma, Brett E. Vakoc, Benjamin J. TI Injury depth control from combined wavelength and power tuning in scanned beam laser thermal therapy SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE laser thermal therapy; laser injury; tissue response; damage model; injury depth control; Barrett's esophagus; thulium fiber laser ID BARRETTS-ESOPHAGUS; RADIOFREQUENCY ABLATION; MICROSCOPY; TISSUE; SKIN; COAGULATION; CELL AB Laser thermal therapy represents a possible method to treat premalignant epithelial lesions of the esophagus. Dynamically conforming the thermal injury profile to a specific lesion boundary is expected to improve the efficacy of such a treatment and avoid complications. In this work, we investigated wavelength tuning as a mechanism to achieve this aimed control over injury depth by using the strong variation of water absorption close to 1900 nm. We developed a numerical model simulating in steps the photon propagation in the tissue, the diffusion of the absorbed heat, and the resulting tissue damage. The model was compared with experimental results on porcine esophageal specimens ex vivo and showed good agreement. Combined with power tuning, the wavelength agility in the range of 1860 to 1895 nm extends the injury range compared to a fixed wavelength source beyond 1 mm, while at the same time improving control over shallow depths and avoiding vaporization at the tissue surface. The combination of two or three discrete wavelengths combined at variable ratios provides similar control, and may provide an improved strategy for the treatment of endothelial lesions. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3647581] C1 [Villiger, Martin] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Villiger, Martin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Villiger, M (reprint author), Harvard Univ, Sch Med, 40 Blossom St,Bartlett Hall 704, Boston, MA 02114 USA. EM mvilliger@partners.org FU National Institutes of Health [R33CA125560, K25CA127465] FX This work was supported by the National Institutes of Health (Grant Nos. R33CA125560 and K25CA127465). NR 29 TC 5 Z9 5 U1 1 U2 7 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV PY 2011 VL 16 IS 11 AR 118001 DI 10.1117/1.3647581 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 868SU UT WOS:000298546500041 PM 22112139 ER PT J AU Bloch, MJ Basile, JN AF Bloch, Michael J. Basile, Jan N. TI New British Guidelines Mandate Ambulatory Blood Pressure Monitoring to Diagnose Hypertension in All Patients: Not Ready for Prime Time in the United States SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Editorial Material C1 [Bloch, Michael J.] St Marys Reg Med Ctr, Risk Reduct Ctr, Reno, NV USA. [Basile, Jan N.] Med Univ S Carolina, Seinsheimer Cardiovasc Hlth Program, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA. [Bloch, Michael J.] Univ Nevada, Sch Med, Dept Internal Med, Reno, NV 89557 USA. [Basile, Jan N.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Bloch, MJ (reprint author), St Marys Reg Med Ctr, Risk Reduct Ctr, 645 N Arlington St,Suite 460, Reno, NV USA. EM mbloch@aol.com NR 1 TC 12 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD NOV PY 2011 VL 13 IS 11 BP 785 EP 786 DI 10.1111/j.1751-7176.2011.00532.x PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 859DG UT WOS:000297854300001 PM 22051420 ER PT J AU Lynch, CP Strom, JL Egede, LE AF Lynch, Cheryl P. Strom, Joni L. Egede, Leonard E. TI Disparities in diabetes self-management and quality of care in rural versus urban veterans SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Veterans; Diabetes; Quality of care; Self-management; Rural health ID GLYCEMIC CONTROL; HEALTH-CARE; ACCESS; TELEMEDICINE; EDUCATION; POLICY AB Background: There are distinct geographic differences in diabetes-related morbidity and mortality; however, data regarding self-management and clinical outcomes are limited. This study examined diabetes care among veterans residing in rural versus urban areas. Methods: A national data set was analyzed based on 10,570 veterans with type 2 diabetes. Residence was determined according to US census-based metropolitan statistical area. Primary outcomes were self-management behaviors (lifestyle and self-monitoring) and quality of care indicators (provider visits, laboratory monitoring and preventive measures). Multivariate analyses were done using STATA v10 to assess the independent effect of veteran residence on each outcome measure and to account for the complex survey design. Results: Among veterans with diabetes, 21.4% were rural residents. Compared to urban veterans, rural veterans had significantly lower education, less annual income and less received diabetes education (P=.002). The final regression model showed that daily foot self-check was the only self-management behavior significantly higher among rural veterans (odds ratio 1.36, 95% confidence interval 1.10-1.70). Provider-based quality of care was not significantly different between groups. Conclusions: Diabetes self-foot care was significantly better among rural veterans than their urban counterparts, but quality of care was equivalent. This suggests that clinical diabetes care among veterans is uniform; however, greater efforts for patient education and support in diabetes self-management are needed to improve outcomes. Published by Elsevier Inc. C1 [Egede, Leonard E.] Med Univ S Carolina, Charleston VA REAP, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. [Lynch, Cheryl P.; Egede, Leonard E.] Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Charleston VA REAP, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. EM egedel@musc.edu FU NIDDK NIH HHS [K24 DK093699] NR 30 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD NOV-DEC PY 2011 VL 25 IS 6 BP 387 EP 392 DI 10.1016/j.jdiacomp.2011.08.003 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 865UA UT WOS:000298335200007 PM 21983152 ER PT J AU Lew, HL Pogoda, TK Baker, E Stolzmann, KL Meterko, M Cifu, DX Amara, J Hendricks, AM AF Lew, Henry L. Pogoda, Terri K. Baker, Errol Stolzmann, Kelly L. Meterko, Mark Cifu, David X. Amara, Jomana Hendricks, Ann M. TI Prevalence of Dual Sensory Impairment and Its Association With Traumatic Brain Injury and Blast Exposure in OEF/OIF Veterans SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE blast injuries; hearing impairment; traumatic brain injury; vision impairment ID VISUAL FUNCTION; POLYTRAUMA; MILITARY; HEARING; IRAQI; WAR; DYSFUNCTION; POPULATION; SOLDIERS; OUTCOMES AB Objective: To describe the prevalence of self-reported rates of auditory, visual, and dual sensory impairment (DSI) in Afghanistan and Iraq war Veterans receiving traumatic brain injury (TBI) evaluations. Design: Retrospective medical chart review. Participants: Thirty-six thousand nine hundred nineteen Veterans who received a TBI evaluation between October 2007 and June 2009. Final sample included 12,521 subjects judged to have deployment-related TBI and a comparison group of 9106 participants with no evidence of TBI. Main Outcome Measure: Self-reported auditory and visual impairment. Results: Self-reported sensory impairment rates were: 34.6% for DSI, 31.3% for auditory impairment only, 9.9% for visual impairment only, and 24.2% for none/mild sensory impairment. Those with TBI and blast exposure had highest rate of DSI. Regression analyses showed that auditory impairment was the strongest predictor of visual impairment, and vice versa, suggesting these impairments may derive from a common source. Conclusions: Veterans who self-report clinically significant hearing or vision difficulty during routine TBI evaluation should be evaluated systematically and comprehensively to determine the extent of sensory impairment. Identifying DSI could allow clinicians to collaborate and maximize rehabilitation. C1 [Pogoda, Terri K.; Stolzmann, Kelly L.; Meterko, Mark] Ctr Org Leadership & Management Res, VA Boston Healthcare Syst, Boston, MA 02130 USA. [Lew, Henry L.] Virginia Commonwealth Univ, Def & Vet Brain Injury Ctr DVBIC, Richmond, VA USA. [Lew, Henry L.; Cifu, David X.] Virginia Commonwealth Univ, Dept Phys Med & Rehabil, Sch Med, Richmond, VA USA. [Pogoda, Terri K.; Meterko, Mark; Hendricks, Ann M.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Cifu, David X.] Hunter Holmes McGuire VA Med Ctr, Phys Med & Rehabil Serv, Richmond, VA USA. [Amara, Jomana] Naval Postgrad Sch, Def Resources Management Inst, Monterey, CA USA. [Hendricks, Ann M.] VA Boston Healthcare Syst, Boston, MA USA. RP Pogoda, TK (reprint author), Ctr Org Leadership & Management Res, VA Boston Healthcare Syst, 150 S Huntington Ave 152M, Boston, MA 02130 USA. EM terri.pogoda@va.gov FU Office of Research and Development, Health Services R&D Service, Department of Veterans Affairs [SDR 08-405] FX This article is based on work supported by the Office of Research and Development, Health Services R&D Service, Department of Veterans Affairs, through SDR 08-405. The study was reviewed and approved by the Institutional Review Board of the VA Boston Healthcare System. NR 33 TC 23 Z9 23 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-9701 J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD NOV-DEC PY 2011 VL 26 IS 6 BP 489 EP 496 DI 10.1097/HTR.0b013e318204e54b PG 8 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 859AC UT WOS:000297845000005 PM 21386715 ER PT J AU Mumenthaler, SM Foo, J Leder, K Choi, NC Agus, DB Pao, W Mallick, P Michor, F AF Mumenthaler, Shannon M. Foo, Jasmine Leder, Kevin Choi, Nathan C. Agus, David B. Pao, William Mallick, Parag Michor, Franziska TI Evolutionary Modeling of Combination Treatment Strategies To Overcome Resistance to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer SO MOLECULAR PHARMACEUTICS LA English DT Article DE non-small cell lung cancer; evolutionary modeling; erlotinib; paclitaxel; resistance; treatment strategies ID PHASE-III TRIAL; DRUG-RESISTANCE; TARGETED THERAPY; EGFR MUTATIONS; GEFITINIB; ERLOTINIB; PACLITAXEL; CARBOPLATIN; TUMORS; CISPLATIN AB Many initially successful anticancer therapies lose effectiveness over time, and eventually, cancer cells acquire resistance to the therapy. Acquired resistance remains a major obstacle to improving remission rates and achieving prolonged disease-free survival. Consequently, novel approaches to overcome or prevent resistance are of significant clinical importance. There has been considerable interest in treating non-small cell lung cancer (NSCLC) with combinations of EGFR-targeted therapeutics (e.g., erlotinib) and cytotoxic therapeutic; (e.g., paclitaxel); however, acquired resistance to erlotinib, driven by a variety of mechanisms, remains an obstacle to treatment success. In about 50% of cases, resistance is due to a T790M point mutation in EGER, and T790M-containing cells ultimately dominate the tumor composition and lead to tumor regrowth. We employed a combined experimental and mathematical modeling-based approach to identify treatment strategies that impede the outgrowth of primary T790M-mediated resistance in NSCLC populations. Our mathematical model predicts the population dynamics of mixtures of sensitive and resistant cells, thereby describing how the tumor composition, initial fraction of resistant cells, and degree of selective pressure influence the time until progression of disease. Model development relied upon quantitative experimental measurements of cell proliferation and death using a novel microscopy approach. Using this approach, we systematically explored the space of combination treatment strategies and demonstrated that optimally timed sequential strategies yielded large improvements in survival outcome relative to monotherapies at the same concentrations. Our investigations revealed regions of the treatment space in which low-dose sequential combination strategies, after predinical validation, may lead to a tumor reduction and improved survival outcome for patients with T790M-mediated resistance. C1 [Mallick, Parag] Stanford Univ, Dept Radiol, Canary Ctr Stanford Canc Early Detect, Palo Alto, CA 94304 USA. [Mumenthaler, Shannon M.; Choi, Nathan C.; Agus, David B.; Mallick, Parag] Univ So Calif, Keck Sch Med, Ctr Appl Mol Med, Los Angeles, CA 90033 USA. [Foo, Jasmine] Univ Minnesota, Sch Math, Minneapolis, MN 55455 USA. [Leder, Kevin] Univ Minnesota, Program Ind & Syst Engn, Minneapolis, MN USA. [Pao, William] Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN USA. [Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Mallick, P (reprint author), Stanford Univ, Dept Radiol, Canary Ctr Stanford Canc Early Detect, 1501 S Calif Ave,Room 2212, Palo Alto, CA 94304 USA. EM paragm@stanford.edu; michor@jimmy.harvard.edu FU National Cancer Institute Cancer Center [P30CA014089]; USC Provost Office; Dean's Development Funds; Keck School of Medicine; National Cancer Institute [U54CA143798, U54CA143907]; CCNE-T [U54CA151459-01] FX The authors would like to thank Thea Tlsty, Philippe Gascard, Luis Estevez-Salmeron, David Liao, Joshua LaBaer, and Laura Gonzalez for their discussion of this project and Mitch Gross for providing his clinical perspective and advice on the manuscript. Cellomics array scan measurements were performed at the USC Broad CIRM Center and Norris Comprehensive Cancer Center Flow Cytometry Core Facility that is supported in part by the National Cancer Institute Cancer Center Shared Grant award P30CA014089 and the USC Provost Office, Dean's Development Funds, Keck School of Medicine. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. This work was funded by National Cancer Institute Grants U54CA143798 and U54CA143907 to establish Physical Sciences-Oncology Centers at the Dana-Farber Cancer Institute and University of Southern California, respectively. In addition, funding support was received from CCNE-T Grant U54CA151459-01. NR 42 TC 22 Z9 24 U1 1 U2 10 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 NOV-DEC PY 2011 VL 8 IS 6 BP 2069 EP 2079 DI 10.1021/mp200270v PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 855BA UT WOS:000297537300011 PM 21995722 ER PT J AU Kuil, J Buckle, T Oldenburg, J Yuan, HS Borowsky, AD Josephson, L van Leeuwen, FWB AF Kuil, Joeri Buckle, Tessa Oldenburg, Joppe Yuan, Hushan Borowsky, Alexander D. Josephson, Lee van Leeuwen, Fijs W. B. TI Hybrid Peptide Dendrimers for Imaging of Chemokine Receptor 4 (CXCR4) Expression SO MOLECULAR PHARMACEUTICS LA English DT Article DE CXCR4; peptides; dendrimers; multimodal hybrid imaging; fluorescence; SPECT/CT ID CARCINOMA IN-SITU; MOUSE MODEL; ANTAGONIST; CANCER; PROBES; CELLS; CONJUGATION; THERAPY; LIGANDS; AMD3100 AB The chemokine receptor 4 (CXCR4), which is overexpressed in many types of cancer, is an emerging target in the field of molecular imaging and therapeutics. The CXCR4 binding of several peptides, including the cyclic Ac-TZ14011, has already been validated. In this study mono-, di- and tetrameric Ac-TZ14011-containing dendrimers were prepared and functionalized with a multimodal (hybrid) label, consisting of a Cy5.5-like fluorophore and a DTPA chelate. Confocal microscopy revealed that all three dendrimers were membrane bound at 4 degrees C, consistent with CXCR4 binding in vitro. The unlabeled dimer and tetrarner had a somewhat lower affinity for CXCR4 than the unlabeled monomer. However, when labeled with the multimodal label the CXCR4 affinity of the dimer and tetramer was considerably higher compared to that of the labeled monomer. On top of that, biodistribution studies revealed that the additional peptides in the dimer and tetramer reduced nonspecific muscle uptake. Thus, multimerization of the cyclic Ac-TZ14011 peptide reduces the negative influence of the multimodal label on the receptor affinity and the biodistribution. C1 [Kuil, Joeri; Buckle, Tessa; van Leeuwen, Fijs W. B.] Leiden Univ, Med Ctr, Dept Radiol, NL-2300 RC Leiden, Netherlands. [Kuil, Joeri; Buckle, Tessa; Oldenburg, Joppe; van Leeuwen, Fijs W. B.] Netherlands Canc Inst, Antoni van Leeuwenhoek Hosp, Div Diagnost Oncol, NL-1066 CX Amsterdam, Netherlands. [Yuan, Hushan; Josephson, Lee] Massachusetts Gen Hosp, Ctr Translat Nucl Med & Mol Imaging, Charlestown, MA 02129 USA. [Yuan, Hushan; Josephson, Lee] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Borowsky, Alexander D.] Univ Calif Davis, Ctr Comparat Med, Sch Med, Dept Pathol & Lab Med, Sacramento, CA 95817 USA. RP van Leeuwen, FWB (reprint author), Leiden Univ, Med Ctr, Dept Radiol, Albinusdreef 2, NL-2300 RC Leiden, Netherlands. EM f.w.b.van_leeuwen@lumc.nl OI van leeuwen, Fijs/0000-0002-6844-4025; Buckle, Tessa/0000-0003-2980-6895 FU KWF [PGF 2009-4344]; CTMM, the 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; F.W.B.v.L.), and within the framework of CTMM, the Centre for Translational Molecular Medicine (http://www.ctmm.nl), project Breast CARE (Grant 030-104; J.K.). NR 52 TC 21 Z9 21 U1 0 U2 27 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 NOV-DEC PY 2011 VL 8 IS 6 BP 2444 EP 2453 DI 10.1021/mp200401p PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 855BA UT WOS:000297537300047 PM 22085282 ER PT J AU Weissleder, R Castro, C AF Weissleder, Ralph Castro, Cesar TI Nanomedicine in oncology: miniaturized means to an enormous end SO NANOMEDICINE LA English DT Editorial Material C1 [Castro, Cesar] Massachusetts Gen Hosp, Div Oncol, Boston, MA 02114 USA. [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Castro, C (reprint author), Massachusetts Gen Hosp, Div Oncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; Castro.Cesar@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 J9 NANOMEDICINE-UK JI Nanomedicine PD NOV PY 2011 VL 6 IS 9 BP 1495 EP 1498 DI 10.2217/NNM.11.138 PG 4 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 860FD UT WOS:000297933300010 PM 22077461 ER PT J AU Murrough, JW Iacoviello, B Neumeister, A Charney, DS Iosifescu, DV AF Murrough, James W. Iacoviello, Brian Neumeister, Alexander Charney, Dennis S. Iosifescu, Dan V. TI Cognitive dysfunction in depression: Neurocircuitry and new therapeutic strategies SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Review DE Depression; Cognition; Neuropsychology; Emotion regulation; Neuroimaging; Therapeutics; Cognitive dysfunction ID OBSESSIVE-COMPULSIVE DISORDER; WHITE-MATTER HYPERINTENSITIES; POSITRON-EMISSION-TOMOGRAPHY; SUBGENUAL PREFRONTAL CORTEX; UNIPOLAR MAJOR DEPRESSION; HAPPY FACIAL EXPRESSIONS; BRAIN GLUCOSE-METABOLISM; STAR-ASTERISK-D; ANTIDEPRESSANT-TREATMENT; EMOTION REGULATION AB Major depressive disorder (MDD) is a disabling medical condition associated with significant morbidity, mortality and public health costs. However, neurocircuitry abnormalities underlying depression remain incompletely understood and consequently current treatment options are unfortunately limited in efficacy. Recent research has begun to focus specifically on cognitive aspects of depression and potential neurobiological correlates. Two fundamental types of cognitive dysfunction observed in MOD are cognitive biases, which include distorted information processing or attentional allocation toward negative stimuli, and cognitive deficits, which include impairments in attention, short-term memory and executive functioning. In this article, we present a selective review of current research findings in these domains and examine neuroimaging research that is beginning to characterize the neurocircuitry underlying these biases and deficits. We propose that deficient cognitive functioning, attention biases and the sustained negative affect characteristic of MOD can be understood as arising in part from dysfunctional prefrontal-subcortical circuitry and related disturbances in the cognitive control of emotion. Finally, we highlight potential new pharmacological and non-pharmacological therapeutic strategies for MDD based on an evolving mechanistic understanding of the disorder. (C) 2011 Elsevier Inc. All rights reserved. C1 [Murrough, James W.; Iacoviello, Brian; Neumeister, Alexander; Iosifescu, Dan V.] Mt Sinai Sch Med, Dept Psychiat, Mood & Anxiety Disorders Program, New York, NY 10029 USA. [Iacoviello, Brian] James J Peters VA Med Ctr, MIRECC, Bronx, NY USA. [Neumeister, Alexander] VA Connecticut Healthcare Syst, Mol Imaging Program, West Haven, CT USA. [Charney, Dennis S.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Charney, Dennis S.] Mt Sinai Sch Med, Dept Syst Pharmacol & Therapeut, New York, NY 10029 USA. [Charney, Dennis S.] Mt Sinai Sch Med, Off Dean, New York, NY 10029 USA. RP Murrough, JW (reprint author), Mt Sinai Sch Med, Dept Psychiat, Mood & Anxiety Disorders Program, Box 1230, New York, NY 10029 USA. EM james.murrough@mssm.edu RI Murrough, James/J-7129-2013 OI Murrough, James/0000-0001-6286-1242 FU Mount Sinai School of Medicine FX Dr. Charney has been named as an inventor on a use-patent of ketamine for the treatment of depression. If ketamine were shown to be effective in the treatment of depression and received approval from the Food and Drug Administration for this indication, Dr. Chamey and the Mount Sinai School of Medicine could benefit financially. All other authors report no completing interests. NR 175 TC 102 Z9 105 U1 17 U2 65 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD NOV PY 2011 VL 96 IS 4 SI SI BP 553 EP 563 DI 10.1016/j.nlm.2011.06.006 PG 11 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 859UD UT WOS:000297900400006 PM 21704176 ER PT J AU McCoy, JG Strecker, RE AF McCoy, John G. Strecker, Robert E. TI The cognitive cost of sleep lost SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Review DE Sleep loss; Learning; Memory; Cognition; Attention; Sleep deprivation; Executive function ID PSYCHOMOTOR VIGILANCE TASK; MORRIS WATER MAZE; DECLARATIVE MEMORY CONSOLIDATION; EXPERIENCE-DEPENDENT CHANGES; LONG-TERM POTENTIATION; ELEVATED PLUS-MAZE; EYE-MOVEMENT SLEEP; REACTION-TIME-TASK; REM-SLEEP; PARADOXICAL SLEEP AB A substantial body of literature supports the intuitive notion that a good night's sleep can facilitate human cognitive performance the next day. Deficits in attention, learning & memory, emotional reactivity, and higher-order cognitive processes, such as executive function and decision making, have all been documented following sleep disruption in humans. Thus, whilst numerous clinical and experimental studies link human sleep disturbance to cognitive deficits, attempts to develop valid and reliable rodent models of these phenomena are fewer, and relatively more recent. This review focuses primarily on the cognitive impairments produced by sleep disruption in rodent models of several human patterns of sleep loss/sleep disturbance. Though not an exclusive list, this review will focus on four specific types of sleep disturbance: total sleep deprivation, experimental sleep fragmentation, selective REM sleep deprivation, and chronic sleep restriction. The use of rodent models can provide greater opportunities to understand the neurobiological changes underlying sleep loss induced cognitive impairments. Thus, this review concludes with a description of recent neurobiological findings concerning the neuroplastic changes and putative brain mechanisms that may underlie the cognitive deficits produced by sleep disturbances. Published by Elsevier Inc. C1 [McCoy, John G.] VA Boston Healthcare Syst, Res Serv, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02301 USA. Stonehill Coll, Dept Psychol, Easton, MA 02357 USA. RP McCoy, JG (reprint author), VA Boston Healthcare Syst, Res Serv, 940 Belmont St,151C, Brockton, MA 02301 USA. EM jmccoy1@stonehill.edu; robert_strecker@hm-s.harvard.edu FU Department of Veterans Affairs Medical Research Service; National Institutes of Health [MH039683, HL060292, HL095491] FX We thank authors of the original work cited, and M. Ali & L Shifflett for assistance with the figures and editorial advice. The writing of this review was supported by the Department of Veterans Affairs Medical Research Service Award, and by the following grants from the National Institutes of Health: MH039683, HL060292, and HL095491. NR 171 TC 64 Z9 67 U1 8 U2 76 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD NOV PY 2011 VL 96 IS 4 SI SI BP 564 EP 582 DI 10.1016/j.nlm.2011.07.004 PG 19 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 859UD UT WOS:000297900400007 PM 21875679 ER PT J AU Bowman, CC Johnson, L Cox, M Rick, C Dougherty, M Alt-White, AC Wyte, T Needleman, J Dobalian, A AF Bowman, Candice C. Johnson, Linda Cox, Malcolm Rick, Catherine Dougherty, Mary Alt-White, Anna C. Wyte, Tamar Needleman, Jack Dobalian, Aram TI The Department of Veterans Affairs Nursing Academy (VANA): Forging strategic alliances with schools of nursing to address nursing's workforce needs SO NURSING OUTLOOK LA English DT Article DE Partnerships; Clinical instruction; Veterans Affairs ID INTERORGANIZATIONAL RELATIONSHIPS; EDUCATION AB In 2007, the Department of Veterans Affairs (VA) established the VA Nursing Academy (VANA), a 5-year, $60-million pilot program funding 15 partnerships between schools of nursing and local VA health care facilities nationwide, to expand nursing faculty, enhance clinical faculty development, increase nursing student enrollment, and promote educational innovations. VA is an ideal setting for educating nursing students owing to a well-educated registered nurse staff, an array of traditional and nontraditional settings, a state-of-the-art computerized electronic health record system, and a unique patient population. Challenges related to the complex nature of VANA partnerships, conceptualized as strategic alliances created between disparate subunits, each embedded in a larger organization, require careful governance to ensure smooth implementation. To ensure the program's aims are met, a 6-year national evaluation has been funded to help identify which strategies best achieve VANA's goals. The speed of economic recovery and the resulting changes in the nursing workforce are important determinants of VANA's future. C1 [Bowman, Candice C.; Wyte, Tamar; Dobalian, Aram] VA Greater Los Angeles Healthcare Syst, HSR&D Ctr Study Healthcare Provider Behav, Sepulveda, CA 91343 USA. [Johnson, Linda; Cox, Malcolm; Rick, Catherine; Dougherty, Mary; Alt-White, Anna C.] Vet Affairs Nursing Acad, Off Acad Affiliat, Dept Vet Affairs, Washington, DC USA. [Needleman, Jack; Dobalian, Aram] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Bowman, CC (reprint author), VA Greater Los Angeles Healthcare Syst, HSR&D Ctr Study Healthcare Provider Behav, 16111 Plummer St 152, Sepulveda, CA 91343 USA. EM candice.bowman@va.gov RI Needleman, Jack/I-5461-2013 OI Needleman, Jack/0000-0002-2875-0589 FU Department of Veterans Affairs, Veterans Health Administration, Office of Academic Affiliations; Department of Veterans Affairs, Veterans Health Administration, Office of Nursing Service FX This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Offices of Academic Affiliations and Nursing Service. NR 31 TC 9 Z9 9 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD NOV-DEC PY 2011 VL 59 IS 6 BP 299 EP 307 DI 10.1016/j.outlook.2011.04.006 PG 9 WC Nursing SC Nursing GA 854IS UT WOS:000297488800003 PM 21684561 ER PT J AU Miller, KK Meenaghan, E Lawson, EA Misra, M Gleysteen, S Schoenfeld, D Herzog, D Klibanski, A AF Miller, Karen K. Meenaghan, Erinne Lawson, Elizabeth A. Misra, Madhusmita Gleysteen, Suzanne Schoenfeld, David Herzog, David Klibanski, Anne TI Effects of Risedronate and Low-Dose Transdermal Testosterone on Bone Mineral Density in Women With Anorexia Nervosa: A Randomized, Placebo-Controlled Study EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Miller, Karen K.] Massachusetts Gen Hosp, Harris Ctr Eating Disorders, Dept Biostat, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Harris Ctr Eating Disorders, Dept Biostat, Neuroendocrine Unit, Boston, MA 02114 USA. 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 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD NOV PY 2011 VL 66 IS 11 BP 690 EP 691 DI 10.1097/OGX.0b013e318234010f PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 865DX UT WOS:000298292100011 ER PT J AU Tache, Y Stengel, A Vaudry, H AF Tache, Yvette Stengel, Andreas Vaudry, Hubert TI Special Issue: Ghrelin SO PEPTIDES LA English DT Editorial Material ID METABOLISM; PEPTIDES; HORMONE C1 [Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Digest Dis Res Ctr Anim Care, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Stengel, Andreas] Obes Ctr Berlin, Div Psychosomat Med, D-10117 Berlin, Germany. [Vaudry, Hubert] Univ Rouen, Inserm U982, Lab Neuronal & Neuroendocrine Differentiat & Comm, Int Associated Lab Samuel de Champlain,European I, F-76821 Mont St Aignan, France. RP Tache, Y (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Digest Dis Res Ctr Anim Care, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,CURE Bldg 115, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu; hubert.vaudry@univ-rouen.fr NR 12 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 0196-9781 J9 PEPTIDES JI Peptides PD NOV PY 2011 VL 32 IS 11 SI SI BP 2151 EP 2152 DI 10.1016/j.peptides.2011.10.015 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 863XO UT WOS:000298201800001 PM 22024141 ER PT J AU Stengel, A Wang, LX Tache, Y AF Stengel, Andreas Wang, Lixin Tache, Yvette TI Stress-related alterations of acyl and desacyl ghrelin circulating levels: Mechanisms and functional implications SO PEPTIDES LA English DT Review DE Abdominal surgery; Food intake; Ghrelin-O-acyltransferase (GOAT); Motility; Somatostatin 2 receptor ID GROWTH-HORMONE SECRETAGOGUE; POSTOPERATIVE GASTRIC ILEUS; GENE-RELATED PEPTIDE; O-ACYLTRANSFERASE GOAT; FASTED PLASMA GHRELIN; ACUTE LUNG INJURY; RAT STOMACH; FOOD-INTAKE; MESSENGER-RNA; RECEPTOR EXPRESSION AB Ghrelin is the only known peripherally produced and centrally acting peptide hormone that stimulates food intake and digestive functions. Ghrelin circulates as acylated and desacylated forms and recently the acylating enzyme, ghrelin-O-acyltransferase (GOAT) and the de-acylating enzyme, thioesterase 1/lysophospholipase 1 have been identified adding new layers of complexity to the regulation of ghrelin. Stress is known to alter gastrointestinal motility and food intake and was recently shown to modify circulating ghrelin and GOAT levels with differential responses related to the type of stressors including a reduction induced by physical stressors (abdominal surgery and immunological/endotoxin injection, exercise) and elevation by metabolic (cold exposure, acute fasting and caloric restriction) and psychological stressors. However, the pathways underlying the alterations of ghrelin under these various stress conditions are still largely to be defined and may relate to stress-associated autonomic changes. There is evidence that alterations of circulating ghrelin may contribute to the neuroendocrine and behavioral responses along with sustaining the energetic requirement needed upon repeated exposure to stressors. A better understanding of these mechanisms will allow targeting components of ghrelin signaling that may improve food intake and gastric motility alterations induced by stress. Published by Elsevier Inc. C1 [Tache, Yvette] VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. [Stengel, Andreas; Wang, Lixin; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Stengel, Andreas; Wang, Lixin; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress & Womens Hlth, Div Digest Dis, Los Angeles, CA 90095 USA. [Stengel, Andreas] Univ Med, Charite, Dept Med, Div Psychosomat Med & Psychotherapy, Berlin, Germany. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM andreas.stengel@charite.de; ytache@mednet.ucla.edu FU VA; NIH [DK-33061, DK-57238] FX Y.T. is recipient of VA Research Career Scientist Award and NIH R01grants DK-33061, DK-57238 and VA Merit Award. We thank Ms. Eugenia Hu for careful reading of the manuscript. NR 141 TC 28 Z9 29 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PD NOV PY 2011 VL 32 IS 11 SI SI BP 2208 EP 2217 DI 10.1016/j.peptides.2011.07.002 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 863XO UT WOS:000298201800007 PM 21782868 ER PT J AU Vu, JP Wang, HS Germano, PM Pisegna, JR AF Vu, John P. Wang, Hank S. Germano, Patrizia M. Pisegna, Joseph R. TI Ghrelin in neuroendocrine tumors SO PEPTIDES LA English DT Review DE Ghrelin; Metastatic neuroendocrine tumors; Endogenous; Orexigenic; Cancer cachexia ID GROWTH-HORMONE SECRETAGOGUE; DES-ACYL GHRELIN; AGOUTI-RELATED PROTEIN; CARCINOID-TUMORS; MESSENGER-RNA; GASTROINTESTINAL-TRACT; ENDOCRINE TUMORS; CHROMOGRANIN-A; SOMATOSTATIN ANALOGS; HELICOBACTER-PYLORI AB Ghrelin is a 28 amino acid peptide, primarily produced by the oxyntic mucosa X/A like neuroendocrine cells in the stomach. It is also found in the small intestine, hypothalamus, pituitary gland, pancreas, heart, adipose tissue, and immune system. In gastrointestinal neuroendocrine tumors (NETs) ghrelin release has been well documented. Ghrelin is a brain-gut circuit peptide with an important role in the physiological regulation of appetite, response to hunger and starvation, metabolic and endocrine functions as energy expenditure, gastric motility and acid secretion, insulin secretion and glucose homeostasis, as well as in the potential connection to the central nervous system. Recently, there has been a significant interest in the biological effects of ghrelin in NETs. In this article, we present a comprehensive review of ghrelin's expression and a brief summary of ghrelin's physiological role in NETs patients with carcinoids, type A chronic atrophic gastritis (CAG), with or without MEN-1, and with and without liver metastases. We hope, with the research reviewed here, to offer compelling evidence of the potential significance of ghrelin in NETs, as well as to provide a useful guide to the future work in this area. Published by Elsevier Inc. C1 [Vu, John P.; Wang, Hank S.; Germano, Patrizia M.; Pisegna, Joseph R.] Vet Adm GIAHS, Dept Gastroenterol & Hepatol, Los Angeles, CA 90073 USA. [Vu, John P.; Wang, Hank S.; Germano, Patrizia M.; Pisegna, Joseph R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Pisegna, JR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Gastroenterol & Hepatol, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jpisegna@ucla.edu NR 73 TC 7 Z9 7 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD NOV PY 2011 VL 32 IS 11 SI SI BP 2340 EP 2347 DI 10.1016/j.peptides.2011.10.006 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 863XO UT WOS:000298201800025 PM 22041110 ER PT J AU Maxwell, CA Benitez, J Gomez-Baldo, L Osorio, A Bonifaci, N Fernandez-Ramires, R Costes, SV Guino, E Chen, H Evans, GJR Mohan, P Catala, I Petit, A Aguilar, H Villanueva, A Aytes, A Serra-Musach, J Rennert, G Lejbkowicz, F Peterlongo, P Manoukian, S Peissel, B Ripamonti, CB Bonanni, B Viel, A Allavena, A Bernard, L Radice, P Friedman, E Kaufman, B Laitman, Y Dubrovsky, M Milgrom, R Jakubowska, A Cybulski, C Gorski, B Jaworska, K Durda, K Sukiennicki, G Lubinski, J Shugart, YY Domchek, SM Letrero, R Weber, BL Hogervorst, FBL Rookus, MA Collee, JM Devilee, P Ligtenberg, MJ van der Luijt, RB Aalfs, CM Waisfisz, Q Wijnen, J van Roozendaal, CEP Easton, DF Peock, S Cook, M Oliver, C Frost, D Harrington, P Evans, DG Lalloo, F Eeles, R Izatt, L Chu, C Eccles, D Douglas, F Brewer, C Nevanlinna, H Heikkinen, T Couch, FJ Lindor, NM Wang, XS Godwin, AK Caligo, MA Lombardi, G Loman, N Karlsson, P Ehrencrona, H von Wachenfeldt, A Barkardottir, RB Hamann, U Rashid, MU Lasa, A Caldes, T Andres, R Schmitt, M Assmann, V Stevens, K Offit, K Curado, J Tilgner, H Guigo, R Aiza, G Brunet, J Castellsague, J Martrat, G Urruticoechea, A Blanco, I Tihomirova, L Goldgar, DE Buys, S John, EM Miron, A Southey, M Daly, MB Schmutzler, RK Wappenschmidt, B Meindl, A Arnold, N Deissler, H Varon-Mateeva, R Sutter, C Niederacher, D Imyamitov, E Sinilnikova, OM Stoppa-Lyonne, D Mazoyer, S Verny-Pierre, C Castera, L de Pauw, A Bignon, YJ Uhrhammer, N Peyrat, JP Vennin, P Ferrer, SF Collonge-Rame, MA Mortemousque, I Spurdle, AB Beesley, J Chen, XQ Healey, S Barcellos-Hoff, MH Vidal, M Gruber, SB Lazaro, C Capella, G McGuffog, L Nathanson, KL Antoniou, AC Chenevix-Trench, G Fleisch, MC Moreno, V Pujana, MA AF Maxwell, Christopher A. Benitez, Javier Gomez-Baldo, Laia Osorio, Ana Bonifaci, Nuria Fernandez-Ramires, Ricardo Costes, Sylvain V. Guino, Elisabet Chen, Helen Evans, Gareth J. R. Mohan, Pooja Catala, Isabel Petit, Anna Aguilar, Helena Villanueva, Alberto Aytes, Alvaro Serra-Musach, Jordi Rennert, Gad Lejbkowicz, Flavio Peterlongo, Paolo Manoukian, Siranoush Peissel, Bernard Ripamonti, Carla B. Bonanni, Bernardo Viel, Alessandra Allavena, Anna Bernard, Loris Radice, Paolo Friedman, Eitan Kaufman, Bella Laitman, Yael Dubrovsky, Maya Milgrom, Roni Jakubowska, Anna Cybulski, Cezary Gorski, Bohdan Jaworska, Katarzyna Durda, Katarzyna Sukiennicki, Grzegorz Lubinski, Jan Shugart, Yin Yao Domchek, Susan M. Letrero, Richard Weber, Barbara L. Hogervorst, Frans B. L. Rookus, Matti A. Collee, J. Margriet Devilee, Peter Ligtenberg, Marjolijn J. van der Luijt, Rob B. Aalfs, Cora M. Waisfisz, Quinten Wijnen, Juul van Roozendaal, Cornelis E. P. Easton, Douglas F. Peock, Susan Cook, Margaret Oliver, Clare Frost, Debra Harrington, Patricia Evans, D. Gareth Lalloo, Fiona Eeles, Rosalind Izatt, Louise Chu, Carol Eccles, Diana Douglas, Fiona Brewer, Carole Nevanlinna, Heli Heikkinen, Tuomas Couch, Fergus J. Lindor, Noralane M. Wang, Xianshu Godwin, Andrew K. Caligo, Maria A. Lombardi, Grazia Loman, Niklas Karlsson, Per Ehrencrona, Hans von Wachenfeldt, Anna Barkardottir, Rosa Bjork Hamann, Ute Rashid, Muhammad U. Lasa, Adriana Caldes, Trinidad Andres, Raquel Schmitt, Michael Assmann, Volker Stevens, Kristen Offit, Kenneth Curado, Joao Tilgner, Hagen Guigo, Roderic Aiza, Gemma Brunet, Joan Castellsague, Joan Martrat, Griselda Urruticoechea, Ander Blanco, Ignacio Tihomirova, Laima Goldgar, David E. Buys, Saundra John, Esther M. Miron, Alexander Southey, Melissa Daly, Mary B. Schmutzler, Rita K. Wappenschmidt, Barbara Meindl, Alfons Arnold, Norbert Deissler, Helmut Varon-Mateeva, Raymonda Sutter, Christian Niederacher, Dieter Imyamitov, Evgeny Sinilnikova, Olga M. Stoppa-Lyonne, Dominique Mazoyer, Sylvie Verny-Pierre, Carole Castera, Laurent de Pauw, Antoine Bignon, Yves-Jean Uhrhammer, Nancy Peyrat, Jean-Philippe Vennin, Philippe Ferrer, Sandra Fert Collonge-Rame, Marie-Agnes Mortemousque, Isabelle Spurdle, Amanda B. Beesley, Jonathan Chen, Xiaoqing Healey, Sue Barcellos-Hoff, Mary Helen Vidal, Marc Gruber, Stephen B. Lazaro, Conxi Capella, Gabriel McGuffog, Lesley Nathanson, Katherine L. Antoniou, Antonis C. Chenevix-Trench, Georgia Fleisch, Markus C. Moreno, Victor Angel Pujana, Miguel CA HEBON EMBRACE SWE-BRCA BCFR GEMO Study Collaborators kConFab TI Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer SO PLOS BIOLOGY LA English DT Article ID CENTROSOMAL MICROTUBULE NUCLEATION; PROGENITOR-CELL FATE; MUTATION CARRIERS; MAMMARY-GLAND; MITOTIC SPINDLE; STEM-CELLS; MULTIPLE-MYELOMA; BRCA1-DEPENDENT UBIQUITINATION; ADHERENS JUNCTIONS; MISSENSE MUTATIONS AB Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM. C1 [Maxwell, Christopher A.; Gomez-Baldo, Laia; Bonifaci, Nuria; Aguilar, Helena; Villanueva, Alberto; Aytes, Alvaro; Serra-Musach, Jordi; Aiza, Gemma; Martrat, Griselda; Urruticoechea, Ander; Angel Pujana, Miguel] Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat, Catalonia, Spain. [Benitez, Javier; Osorio, Ana; Fernandez-Ramires, Ricardo] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Madrid, Spain. [Bonifaci, Nuria; Guino, Elisabet; Serra-Musach, Jordi; Moreno, Victor; Angel Pujana, Miguel] IDIBELL, Catalan Inst Oncol, Biomarkers & Susceptibil Unit, Lhospitalet De Llobregat, Catalonia, Spain. [Costes, Sylvain V.; Barcellos-Hoff, Mary Helen] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA. [Catala, Isabel; Petit, Anna] Univ Hosp Bellvitge, IDIBELL, Dept Pathol, Lhospitalet De Llobregat, Catalonia, Spain. [Rennert, Gad; Lejbkowicz, Flavio] Technion Israel Inst Technol, Carmel Med Ctr, Dept Community Med & Epidemiol, CHS Natl Canc Control Ctr, Haifa, Israel. [Rennert, Gad; Lejbkowicz, Flavio] Technion Israel Inst Technol, B Rappaport Fac Med, Haifa, Israel. [Peterlongo, Paolo; Ripamonti, Carla B.; Radice, Paolo] Fdn IRCCS, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Ist Nazl Tumori, Milan, Italy. [Peterlongo, Paolo; Ripamonti, Carla B.; Radice, Paolo] IFOM Fdn, Ist FIRC Oncol Mol, Milan, Italy. [Manoukian, Siranoush; Peissel, Bernard; Ripamonti, Carla B.] Fdn IRCCS, Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy. [Bonanni, Bernardo] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy. [Viel, Alessandra] IRCCS, Ctr Riferimento Oncol, Div Expt Oncol 1, Aviano, Italy. [Allavena, Anna] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy. [Bernard, Loris] Ist Europeo Oncol, Dept Expt Oncol, Milan, Italy. [Bernard, Loris] Consortium Genom Technol Cogentech, Milan, Italy. [Friedman, Eitan; Kaufman, Bella; Laitman, Yael; Dubrovsky, Maya; Milgrom, Roni] Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, Ramat Gan, Israel. [Friedman, Eitan] Tel Aviv Univ, Sackler Fac Med, Ramat Aviv, Israel. [Jakubowska, Anna; Cybulski, Cezary; Gorski, Bohdan; Jaworska, Katarzyna; Durda, Katarzyna; Sukiennicki, Grzegorz; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland. [Shugart, Yin Yao] NIMH, Unit Stat Genet, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Domchek, Susan M.; Letrero, Richard; Weber, Barbara L.; Nathanson, Katherine L.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Hogervorst, Frans B. L.] Netherlands Canc Inst, Dept Pathol, Family Canc Clin, NL-1066 CX Amsterdam, Netherlands. [Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Collee, J. Margriet] Erasmus Univ, Dept Clin Genet, Med Ctr, Rotterdam Family Canc Clin, NL-3000 DR Rotterdam, Netherlands. [Devilee, Peter] Leiden Univ, Dept Genet Epidemiol, Med Ctr, Leiden, Netherlands. [Ligtenberg, Marjolijn J.] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [van der Luijt, Rob B.] Univ Utrecht, Med Ctr, Dept Clin Mol Genet, Utrecht, Netherlands. [Aalfs, Cora M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Waisfisz, Quinten] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [Wijnen, Juul] Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Leiden, Netherlands. [van Roozendaal, Cornelis E. P.] Univ Med Ctr, Dept Clin Genet, Maastricht, Netherlands. [Easton, Douglas F.; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; McGuffog, Lesley; Antoniou, Antonis C.; EMBRACE] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Harrington, Patricia] Univ Cambridge, Dept Oncol, Cambridge, England. [Evans, D. Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. [Izatt, Louise] Guys & St Thomas NHS Fdn Trust, London, England. [Chu, Carol] St James Hosp, Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Eccles, Diana] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Douglas, Fiona] Newcastle Upon Tyne Hosp NHS Trust, Ctr Life, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England. [Brewer, Carole] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England. [Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Lindor, Noralane M.] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA. [Caligo, Maria A.; Lombardi, Grazia] Univ Pisa, Sect Genet Oncol, Dept Oncol, Pisa, Italy. [Caligo, Maria A.; Lombardi, Grazia] Univ Hosp Pisa, Dept Lab Med, Pisa, Italy. [Loman, Niklas] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden. [Karlsson, Per] Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden. [Ehrencrona, Hans] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden. [von Wachenfeldt, Anna] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Barkardottir, Rosa Bjork] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland. [Hamann, Ute; Rashid, Muhammad U.] Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. [Rashid, Muhammad U.] Shaukat Khanum Mem Canc Hosp & Res Ctr, Dept Basic Sci, Lahore, Pakistan. [Lasa, Adriana] Hosp Santa Creu & Sant Pau, Genet Serv, Barcelona, Catalonia, Spain. [Caldes, Trinidad] Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain. [Andres, Raquel] Hosp Clin Zaragoza, Div Med Oncol, Zaragoza, Spain. [Schmitt, Michael] Univ Rostock, Dept Internal Med 3, Rostock, Germany. [Assmann, Volker] Univ Hosp Hamburg Eppendorf, Inst Tumor Biol, Ctr Med Expt, Hamburg, Germany. [Stevens, Kristen] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. [Curado, Joao; Tilgner, Hagen; Guigo, Roderic] Biomed Res Pk Barcelona PRBB, Ctr Genom Regulat CRG, Bioinformat & Genom Grp, Barcelona, Catalonia, Spain. [Brunet, Joan; Castellsague, Joan; Blanco, Ignacio; Lazaro, Conxi; Capella, Gabriel] Girona Biomed Res Inst IdIBGi, Catalonia, Spain. [Brunet, Joan; Castellsague, Joan; Blanco, Ignacio; Lazaro, Conxi; Capella, Gabriel] IDIBELL, Catalan Inst Oncol, Genet Counseling & Hereditary Canc Programme, Catalonia, Spain. [Tihomirova, Laima] Latvian Biomed Res & Study Ctr, Riga, Latvia. [Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. [Buys, Saundra] Huntsman Canc Inst, Dept Internal Med, Salt Lake City, UT USA. [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA. [Miron, Alexander] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Miron, Alexander] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Southey, Melissa] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt MEGA Epidemiol, Melbourne, Vic 3010, Australia. [Daly, Mary B.] Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Cologne, Ctr Familial Breast & Ovarian Canc, D-50931 Cologne, Germany. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany. [Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Dept Obstet & Gynaecol, D-8000 Munich, Germany. [Arnold, Norbert] Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, Div Oncol, Kiel, Germany. [Deissler, Helmut] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany. [Varon-Mateeva, Raymonda] Charite, Inst Humangenet, D-13353 Berlin, Germany. [Sutter, Christian] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany. [Niederacher, Dieter] Univ Dusseldorf, Ctr Clin, Dept Obstet & Gynaecol, Div Mol Genet, D-40225 Dusseldorf, Germany. [Imyamitov, Evgeny] NN Petrov Inst Oncol, St Petersburg, Russia. [Sinilnikova, Olga M.] CHU Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. [Sinilnikova, Olga M.; Mazoyer, Sylvie; Verny-Pierre, Carole] Univ Lyon, Ctr Leon Berard, CNRS UMR5201, Equipe Labellisee LIGUE 2008, Lyon, France. [Stoppa-Lyonne, Dominique; Castera, Laurent; de Pauw, Antoine] Univ Paris 05, Serv Genet Oncol, INSERM, Inst Curie,U509, Paris, France. [Bignon, Yves-Jean; Uhrhammer, Nancy] Univ Clermont Ferrand, Ctr Jean Perrin, Dept Oncogenet, Clermont Ferrand, France. [Peyrat, Jean-Philippe] Ctr Oscar Lambret, Lab Oncol Mol Humaine, F-59020 Lille, France. [Ferrer, Sandra Fert] Hotel Dieu Ctr Hosp, Lab Genet Chromosom, Chambery, France. [Collonge-Rame, Marie-Agnes] CHU Besancon, Serv Genet Histol Biol Dev & Reprod, F-25030 Besancon, France. [Mortemousque, Isabelle] CHU Bretonneau, Serv Genet, F-37044 Tours, France. [Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Healey, Sue; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. Peter MacCallum Canc Inst, Kathleen Cuningham Fdn, Consortium Res Familial Breast Canc, Melbourne, Australia. [Vidal, Marc] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Vidal, Marc] Harvard Univ, Sch Med, Ctr Canc Syst Biol CCSB, Boston, MA USA. [Gruber, Stephen B.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Fleisch, Markus C.] Univ Dusseldorf, Dept Obstet & Gynaecol, D-40225 Dusseldorf, Germany. RP Maxwell, CA (reprint author), Child & Family Res Inst, Dept Pediat, Vancouver, BC, Canada. EM cmaxwell@cfri.ubc.ca; mapujana@ico.scs.es RI Spurdle, Amanda/A-4978-2011; Jakubowska, Anna/O-8050-2014; Guigo, Roderic/D-1303-2010; Ligtenberg, Marjolijn/N-9666-2013; Fernandez-Ramires, Ricardo/H-3707-2014; Ripamonti, Carla Barbara/D-2247-2017; manoukian, siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; Ehrencrona, Hans/M-5619-2014; pujana, Miguel Angel/N-3127-2014; Arnold, Norbert/E-3012-2010; Maxwell, Christopher/B-3044-2011; Costes, Sylvain/D-2522-2013; Radice, Paolo/O-3119-2013; Aytes, Alvaro/B-5803-2014; Blanco, Ignacio/D-2565-2013; Fleisch, Markus/E-4134-2014; Osorio, Ana/I-4324-2014; Bernard, Loris/K-5953-2014; Aytes, Alvaro/M-1360-2014 OI Evans, Gareth/0000-0002-8482-5784; Spurdle, Amanda/0000-0003-1337-7897; Brunet, Joan/0000-0003-1945-3512; Nevanlinna, Heli/0000-0002-0916-2976; Moreno, Victor/0000-0002-2818-5487; Guigo, Roderic/0000-0002-5738-4477; Ligtenberg, Marjolijn/0000-0003-1290-1474; Ripamonti, Carla Barbara/0000-0002-2892-8164; manoukian, siranoush/0000-0002-6034-7562; Peissel, Bernard/0000-0001-9233-3571; Eeles, Rosalind/0000-0002-3698-6241; Nathanson, Katherine/0000-0002-6740-0901; Ehrencrona, Hans/0000-0002-5589-3622; pujana, Miguel Angel/0000-0003-3222-4044; Arnold, Norbert/0000-0003-4523-8808; Maxwell, Christopher/0000-0002-0860-4031; Costes, Sylvain/0000-0002-8542-2389; Aytes, Alvaro/0000-0003-0725-5340; Blanco, Ignacio/0000-0002-7414-7481; Fleisch, Markus/0000-0002-8966-4721; Osorio, Ana/0000-0001-8124-3984; Aytes, Alvaro/0000-0003-0725-5340 FU Spanish Ministries of Health, and Science ane Innovation [CB07/02/2005]; FIS [08/1120, 08/1359, 08/1635, 09/02483]; RTICCC [RD06/0020/1060, RD06/0020/0028]; Transversal Action Against Cancer; Spanish Biomedical Research Centre Networks for Epidemiology and Public Health, and Rare Diseases; "Ramon y Cajal" Young Investigator Program; Spanish National Society of Medical Oncology; Spanish Association Against Cancer [AECC 2010]; AGAUR Catalan Government Agency [2009SGR1489, 2009SGR293]; Beatriu Pinos Postdoctoral Program; Ramon Areces Foundation; "Roses Contra el Cancer" Foundation; Michael Cuccione Foundation for Childhood Cancer Research, Cancer Research-UK [C490/A10119, C1287/A8874, C1287/A10118, C5047/A8385, C8197/A10123]; National Institute for Health Research (UK); Association for International Cancer Research [AICR-07-0454]; Ligue National Contre le Cancer (France); Association "Le cancer du sein, parlons-en!"; Dutch Cancer Society [NKI 1998-1854, 2004-3088, 2007-3756]; Fondazione Italiana per la Ricerca sul Cancro ("Hereditary Tumors"); Associazione Italiana per la Ricerca sul Cancro [4017]; Italian Ministero della Salute [RFPS-2006-3-340203]; Italian Ministero dell'Universita e Ricerca [RBLAO3-BETH]; Fondazione IRCCS Istituto Nazionale Tumori [INT "5x1000"]; Fondazione Cassa di Risparmio di Pisa (Istituto Toscano Tumori); National Breast Cancer Foundation (Australia); Australian National Health and Medical Research Council [145684, 288704, 454508]; Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia; Cancer Foundation of Western Australia; German Cancer Aid [107054]; Center for Molecular Medicine Cologne [TV93]; National Cancer Institute (USA) [CA128978, CA122340]; National Institutes of Health [RFA-CA-06-503, BCFR U01 CA69398, CA69417, CA69446, CA69467, CA69631, CA69638]; Research Triangle Institute Informatics Support Center [RFP N02PC45022-46]; Specialized Program of Research Excellence (SPORE) [P50 CA83638, CA113916]; Department of Defense [05/0612]; Eileen Stein Jacoby Fund; Breast Cancer Research Foundation; Marianne and Robert MacDonald Foundation; Komen Foundation; Helsinki University Central Hospital; Academy of Finland [110663]; Finnish Cancer Society; Sigrid Juselius Foundation; EU [223175, HEALTH-F2-2009-223175] FX This work was funded by the Spanish Ministries of Health, and Science ane Innovation (CB07/02/2005; FIS 08/1120, 08/1359, 08/1635, and 09/02483; RTICCC RD06/0020/1060 and RD06/0020/0028; Transversal Action Against Cancer; the Spanish Biomedical Research Centre Networks for Epidemiology and Public Health, and Rare Diseases; and the "Ramon y Cajal" Young Investigator Program), the Spanish National Society of Medical Oncology (2010), the Spanish Association Against Cancer (AECC 2010), the AGAUR Catalan Government Agency (2009SGR1489 and 2009SGR293; and the Beatriu Pinos Postdoctoral Program), the Ramon Areces Foundation (XV), the "Roses Contra el Cancer" Foundation, the Michael Cuccione Foundation for Childhood Cancer Research, Cancer Research-UK (C490/A10119, C1287/A8874, C1287/A10118, C5047/A8385, and C8197/A10123), the National Institute for Health Research (UK), the Association for International Cancer Research (AICR-07-0454), the Ligue National Contre le Cancer (France), the Association "Le cancer du sein, parlons-en!", the Dutch Cancer Society (NKI 1998-1854, 2004-3088, and 2007-3756), the Fondazione Italiana per la Ricerca sul Cancro ("Hereditary Tumors"), the Associazione Italiana per la Ricerca sul Cancro (4017), the Italian Ministero della Salute (RFPS-2006-3-340203 and "Progetto Tumori Femminili"), the Italian Ministero dell'Universita e Ricerca (RBLAO3-BETH), the Fondazione IRCCS Istituto Nazionale Tumori (INT "5x1000"), the Fondazione Cassa di Risparmio di Pisa (Istituto Toscano Tumori), the National Breast Cancer Foundation (Australia), the Australian National Health and Medical Research Council (145684, 288704, and 454508), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, the Cancer Foundation of Western Australia, the German Cancer Aid (107054), the Center for Molecular Medicine Cologne (TV93), the National Cancer Institute (USA; CA128978 and CA122340), National Institutes of Health (RFA-CA-06-503, BCFR U01 CA69398, CA69417, CA69446, CA69467, CA69631, and CA69638), the Research Triangle Institute Informatics Support Center (RFP N02PC45022-46), the Specialized Program of Research Excellence (SPORE P50 CA83638 and CA113916), the Department of Defense Breast Cancer Research Program (05/0612), the Eileen Stein Jacoby Fund, the Breast Cancer Research Foundation, the Marianne and Robert MacDonald Foundation, the Komen Foundation, the Helsinki University Central Hospital Research Fund, the Academy of Finland (110663), the Finnish Cancer Society, the Sigrid Juselius Foundation, and the EU FP7 (223175, HEALTH-F2-2009-223175). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 28 Z9 28 U1 1 U2 19 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD NOV PY 2011 VL 9 IS 11 AR e1001199 DI 10.1371/journal.pbio.1001199 PG 18 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 863HE UT WOS:000298152600012 PM 22110403 ER PT J AU Peng, RR Wang, AL Li, J Tucker, JD Yin, YP Chen, XS AF Peng, Rui-Rui Wang, Alberta L. Li, Jing Tucker, Joseph D. Yin, Yue-Ping Chen, Xiang-Sheng TI Molecular Typing of Treponema pallidum: A Systematic Review and Meta-Analysis SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Review ID MACROLIDE RESISTANCE; SECONDARY SYPHILIS; TREATMENT FAILURE; AZITHROMYCIN RESISTANCE; SUBSP PALLIDUM; SAN-FRANCISCO; SOUTH-AFRICA; STRAINS; CHINA; BLOOD AB Background: Syphilis is resurgent in many regions of the world. Molecular typing is a robust tool for investigating strain diversity and epidemiology. This study aimed to review original research on molecular typing of Treponema pallidum (T. pallidum) with three objectives: (1) to determine specimen types most suitable for molecular typing; (2) to determine T. pallidum subtype distribution across geographic areas; and (3) to summarize available information on subtypes associated with neurosyphilis and macrolide resistance. Methodology/Principal Findings: Two researchers independently searched five databases from 1998 through 2010, assessed for eligibility and study quality, and extracted data. Search terms included "Treponema pallidum," or "syphilis," combined with the subject headings "molecular," "subtyping," "typing," "genotype," and "epidemiology." Sixteen eligible studies were included. Publication bias was not statistically significant by the Begg rank correlation test. Medians, inter-quartile ranges, and 95% confidence intervals were determined for DNA extraction and full typing efficiency. A random-effects model was used to perform subgroup analyses to reduce obvious between-study heterogeneity. Primary and secondary lesions and ear lobe blood specimens had an average higher yield of T. pallidum DNA (83.0% vs. 28.2%, chi(2) = 247.6, p<0.001) and an average higher efficiency of full molecular typing (80.9% vs. 43.1%, chi(2) = 102.3, p<0.001) compared to plasma, whole blood, and cerebrospinal fluid. A pooled analysis of subtype distribution based on country location showed that 14d was the most common subtype, and subtype distribution varied across geographic areas. Subtype data associated with macrolide resistance and neurosyphilis were limited. Conclusions/Significance: Primary lesion was a better specimen for obtaining T. pallidum DNA than blood. There was wide geographic variation in T. pallidum subtypes. More research is needed on the relationship between clinical presentation and subtype, and further validation of ear lobe blood for obtaining T. pallidum DNA would be useful for future molecular studies of syphilis. C1 [Peng, Rui-Rui; Wang, Alberta L.; Li, Jing; Yin, Yue-Ping; Chen, Xiang-Sheng] Chinese Acad Med Sci, Natl Ctr STD Control, Nanjing, Peoples R China. [Peng, Rui-Rui; Wang, Alberta L.; Li, Jing; Yin, Yue-Ping; Chen, Xiang-Sheng] Peking Union Med Coll, Inst Dermatol, Nanjing, Peoples R China. [Wang, Alberta L.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Tucker, Joseph D.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Peng, RR (reprint author), Chinese Acad Med Sci, Natl Ctr STD Control, Nanjing, Peoples R China. EM chenxs@ncstdlc.org FU Mega Project of the China National Science Research for the 11th Five-Year Plan [2008ZX10001-005]; NIAID/UNC STI/TM Cooperative Research Center [5U19 AI031496-18] FX This study was supported by grants from the Mega Project of the China National Science Research for the 11th Five-Year Plan (2008ZX10001-005) and the NIAID/UNC STI/TM Cooperative Research Center (5U19 AI031496-18). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 16 Z9 19 U1 0 U2 11 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 NOV PY 2011 VL 5 IS 11 AR e1273 DI 10.1371/journal.pntd.0001273 PG 8 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 863AA UT WOS:000298134000002 PM 22087340 ER PT J AU Maestas, KL Benge, JF Pastorek, NJ LeMaire, A Darrow, R AF Maestas, Kacey Little Benge, Jared F. Pastorek, Nicholas J. LeMaire, Ashley Darrow, Rachel TI Factor Structure of Posttraumatic Stress Disorder Symptoms in OEF/OIF Veterans Presenting to a Polytrauma Clinic SO REHABILITATION PSYCHOLOGY LA English DT Article DE factor analysis; posttraumatic stress; veterans; mild traumatic brain injury ID TRAUMATIC BRAIN-INJURY; CONFIRMATORY FACTOR-ANALYSIS; PERSISTENT POSTCONCUSSIVE SYMPTOMS; MEASUREMENT INVARIANCE; WAR VETERANS; CHRONIC PAIN; CHECKLIST; COMBAT; IRAQ; AFGHANISTAN AB Objective: A significant number of Operation Iraqi Freedom/Operation Enduring Freedom (OEF/OIF) veterans are returning from deployment and presenting to Veterans Health Administration (VHA) polytrauma clinics with elevated rates of posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI). Inherent to the accurate assessment and treatment of this diagnostically complex group of veterans is the assumption that the construct of PTSD is the same in this population as in other trauma groups. To our knowledge, no previous study has examined the structure of PTSD in this relevant and fast-growing population of treatment-seeking OEF/OIF veterans. Evidence suggests that the latent structure of PTSD symptoms is best represented by a four-factor model, rather than the three-factor model found in the current DSM-IV-TR. Thus, we examined the three and four-factor models using the PTSD Check List-Civilian (PCL-C) in a sample of treatment-seeking OEF/OIF veterans seen through a VHA polytrauma clinic. Method: A chart review was conducted for OEF/OIF veterans (N = 361) seen through a VHA outpatient polytrauma clinic from September 2007 through August 2008. Participants completed the PCL-C as part of a comprehensive polytrauma evaluation. Results: Confirmatory factor analyses showed that the DSM-IV-TR three-factor model did not fit the data well. A direct comparison showed that the four-factor model provided a superior fit relative to the three-factor model. Conclusion: Results extend the generalizability of the four-factor model to OEF/OIF veterans presenting to Veterans Health Administration (VHA) polytrauma clinics. C1 [Maestas, Kacey Little] Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Maestas, Kacey Little; Pastorek, Nicholas J.] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. [Benge, Jared F.; Pastorek, Nicholas J.] Jack C Montgomery VA Med Ctr, Rehabil Care Line, Muskogee, OK USA. [LeMaire, Ashley] Mem Hosp Gulfport, Dept Neurosci & Rehabil, Gulfport, MS USA. [Darrow, Rachel] Ralph H Johnson VA Med Ctr, Mental Hlth Care Line, Charleston, SC USA. RP Pastorek, NJ (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd,RCL 117, Houston, TX 77030 USA. EM nicholas.pastorek@va.gov RI Schueter, nicos/A-3625-2014 NR 51 TC 7 Z9 7 U1 2 U2 6 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD NOV PY 2011 VL 56 IS 4 BP 366 EP 373 DI 10.1037/a0025447 PG 8 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA 862AQ UT WOS:000298062600010 PM 21928917 ER PT J AU Scalapino, KJ Thomas, CR AF Scalapino, Kenneth J. Thomas, Charles R., Jr. TI Preface Paraneoplastic and Cancer Treatment-Related Rheumatic Disorders SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Scalapino, Kenneth J.] Portland VA Med Ctr, Rheumatol Sect, Portland, OR 97239 USA. [Thomas, Charles R., Jr.] Oregon Hlth & Sci Univ, Knight Canc Inst, Dept Radiat Med, Portland, OR 97239 USA. RP Scalapino, KJ (reprint author), Portland VA Med Ctr, Rheumatol Sect, 3710 SW US Verterans Hosp Rd, Portland, OR 97239 USA. EM Kenneth.Scalapino@va.gov; thomasch@ohsu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 2011 VL 37 IS 4 BP IX EP X DI 10.1016/j.rdc.2011.09.005 PG 2 WC Rheumatology SC Rheumatology GA 865KU UT WOS:000298310600001 PM 22075202 ER PT J AU Ashouri, JF Daikh, DI AF Ashouri, Judith F. Daikh, David I. TI Rheumatic Manifestations of Cancer SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article DE Malignancy; Paraneoplastic manifestation; Rheumatic disease; Fasciitis; POEMS; Inflammatory myopathy ID SERONEGATIVE SYMMETRICAL SYNOVITIS; ENDOTHELIAL GROWTH-FACTOR; POPULATION-BASED COHORT; HENOCH-SCHONLEIN PURPURA; GIANT-CELL ARTERITIS; PRIMARY HYPERTROPHIC OSTEOARTHROPATHY; ASPARTATE RECEPTOR ENCEPHALITIS; FASCIITIS-PANNICULITIS SYNDROME; DERMATOMYOSITIS SINE MYOSITIS; PITTING EDEMA SYNDROME AB The wide range of rheumatic and musculoskeletal conditions that can appear in association with cancer emphasizes that rheumatic disease is a major component of the spectrum of paraneoplastic manifestations. Although the pathogenetic mechanisms by which neoplasia causes these manifestations are only partially understood in select cases, many are because of immune-mediated effects stimulated by tumor antigens of endocrine factors produced by tumors. The broad overlap in signs and symptoms of occult malignancy and systemic rheumatic disease emphasizes the importance of considering and investigating the possibility of occult malignancy in the evaluation of patients with these symptoms. C1 [Ashouri, Judith F.; Daikh, David I.] Univ Calif San Francisco, Dept Med, Div Rheumatol, San Francisco, CA 94143 USA. [Ashouri, Judith F.; Daikh, David I.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. RP Daikh, DI (reprint author), Univ Calif San Francisco, Dept Med, Div Rheumatol, 400 Parnassus, San Francisco, CA 94143 USA. EM david.daikh@ucsf.edu NR 156 TC 2 Z9 2 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 2011 VL 37 IS 4 BP 489 EP + DI 10.1016/j.rdc.2011.09.001 PG 18 WC Rheumatology SC Rheumatology GA 865KU UT WOS:000298310600002 PM 22075194 ER PT J AU Lipton, S Schwab, P AF Lipton, Sarah Schwab, Pascale TI Neoplasm Mimics of Rheumatologic Presentations: Sialadenitis, Ocular Masquerade Syndromes, Retroperitoneal Fibrosis, and Regional Pain Syndromes SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article DE Cancer; Sialadenitis; IgG4-related syndrome; Ocular masquerade syndrome; Retroperitoneal fibrosis; Complex regional pain syndrome; Amyloidosis ID REFLEX SYMPATHETIC DYSTROPHY; DIFFUSE INFILTRATING RETINOBLASTOMA; IGG4-RELATED SCLEROSING DISEASE; PRIMARY INTRAOCULAR LYMPHOMA; PRIMARY SYSTEMIC AMYLOIDOSIS; SALIVARY-GLAND TUMORS; SJOGRENS-SYNDROME; CLINICAL-FEATURES; MIKULICZS-DISEASE; LONG-TERM AB This article reviews a group of miscellaneous malignant conditions that may mimic rheumatologic diseases. Primary salivary gland cancer as well as lymphoproliferative conditions such as lymphoma and IgG4 related syndromes should be considered when evaluating a patient with sialadenosis. Primary intraocular lymphoma and melanoma in adults as well as leukemia and retinoblastoma in children may present as idiopathic ocular inflammation and require a high index of suspicion. Retroperitoneal fibrosis may mimic lymphoma or a solid malignancy and poses diagnostic challenges. Regional pain syndromes, such as complex regional pain and carpal tunnel syndromes, may be a manifestation of cancer and amyloidosis respectively. Awareness of these rare mimics may serve in guiding diagnostic investigations. C1 [Lipton, Sarah; Schwab, Pascale] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Div Arthrit & Rheumat Dis, Portland, OR 97239 USA. RP Schwab, P (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Div Arthrit & Rheumat Dis, 3181 SW Sam Jackson Pk Rd,OP09, Portland, OR 97239 USA. EM schwabp@ohsu.edu NR 100 TC 1 Z9 1 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-857X EI 1558-3163 J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 2011 VL 37 IS 4 BP 623 EP + DI 10.1016/j.rdc.2011.09.004 PG 17 WC Rheumatology SC Rheumatology GA 865KU UT WOS:000298310600009 PM 22075201 ER PT J AU Schaefer, EAK Chung, RT AF Schaefer, Esperance A. K. Chung, Raymond T. TI The Impact of Human Gene Polymorphisms on HCV Infection and Disease Outcome SO SEMINARS IN LIVER DISEASE LA English DT Review DE Hepatitis C; IL28B; IFN lambda; PNPLA3; ITPA ID CHRONIC HEPATITIS-C; VIRUS-COINFECTED PATIENTS; FATTY LIVER-DISEASE; ALPHA-2A PLUS RIBAVIRIN; GENOTYPE 1 INFECTION; JAK-STAT PATHWAY; SPONTANEOUS CLEARANCE; PEGYLATED INTERFERON; INTERLEUKIN 28B; IL28B GENOTYPE AB In recent years, some genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with hepatitis C viral containment, treatment response, and disease progression. IL28B is a gene on chromosome 19, coding for interferon-lambda 3, and two polymorphisms upstream of this the gene have been strongly associated with clinical outcomes after treatment for the hepatitis C virus (HCV). The IL28B polymorphisms have additionally been associated with spontaneous clearance. The mechanism has yet to be clearly defined, but appears to involve differential responsiveness to interferon signaling between the favorable and unfavorable genotypes. ITPA is a gene on chromosome 20, coding for inosine triphosphatase, and polymorphisms on this gene have been associated with ribavirin-induced hemolytic anemia. Functional variants of ITPA have been identified that have decreased enzymatic activity, which appear to protect against anemia. Finally, PNPLA3 polymorphisms were initially described as predictors of non-alcoholic fatty liver disease, but have recently been associated with disease progression in HCV. C1 [Schaefer, Esperance A. K.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, GI Unit, Boston, MA 02114 USA. RP Schaefer, EAK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, GI Unit, 55 Fruit St, Boston, MA 02114 USA. EM eschaefer@partners.org NR 92 TC 12 Z9 12 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD NOV PY 2011 VL 31 IS 4 BP 375 EP 386 DI 10.1055/s-0031-1297926 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 866QS UT WOS:000298396900006 PM 22189977 ER PT J AU Nelson, CC Sapp, A Berkman, LF Li, Y Sorensen, G AF Nelson, Candace C. Sapp, Amy Berkman, Lisa F. Li, Yi Sorensen, Glorian TI Allocation of household responsibilities influences change in dietary behavior SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Nutrition; Food choice; Dietary behavior; Work-family; USA; Family roles; Household labor; Households; Gender ID FACTOR SURVEILLANCE SYSTEM; WORK-FAMILY SPILLOVER; FOOD CHOICE; VEGETABLE CONSUMPTION; HEALTHY DIRECTIONS; UNITED-STATES; LOW-INCOME; FRUIT; ADULTS; RISK AB This study was undertaken to understand dietary behavior as situated within the household, an important social context that serves to either inhibit or promote a healthy diet. Data were collected as part of a worksite-based health behavior intervention trial that took place between 1999 and 2003 in small manufacturing businesses in New England, USA. The subjects were a cohort of 790 male and female workers who participated in the intervention trial and responded to both the baseline and the 18-month follow-up surveys. Regression models were built to determine whether proportion of household responsibility predicted daily fruit and vegetable consumption and weekly red meat consumption at 18-months. The results indicate that participants who were responsible for earning most or all of the money to support the household ate more servings of fruits and vegetables per day at 18-month follow-up than those without this responsibility. Further, those responsible for earning about half ate fewer servings of red meat than those responsible for earning most or all of the money to support the household. The results for red meat consumption differed by sex, such that responsibility for more than half or less than half of the money to support the household had different effects for men and women. The results of this study demonstrate that the distribution of household responsibilities can be an important factor in determining the effectiveness of a worksite-based health behavior intervention and that these effects can be different for women versus men. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Nelson, Candace C.; Sapp, Amy] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA USA. [Li, Yi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Berkman, Lisa F.] Harvard Ctr Populat & Dev Studies, Cambridge, MA USA. RP Nelson, CC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM candace_nelson@post.harvard.edu FU National Cancer Institute [5 P01 CA 75308-03] FX This work was supported by a grant from the National Cancer Institute (grant 5 P01 CA 75308-03). The authors wish to express their gratitude to the small businesses who participated in this study. We also thank the anonymous reviewers for their comments on earlier versions of the article. NR 32 TC 1 Z9 1 U1 4 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD NOV PY 2011 VL 73 IS 10 BP 1517 EP 1524 DI 10.1016/j.socscimed.2011.08.030 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 859WI UT WOS:000297906100010 PM 21975026 ER PT J AU Gordon, CR Abouhassan, W Avery, RK AF Gordon, C. R. Abouhassan, W. Avery, R. K. TI What Is The True Significance of Donor-Related Cytomegalovirus Transmission in the Setting of Facial Composite Tissue Allotransplantation? SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 10th International Congress of the Hand-and-Composite-Tissue-Allotransplantation-Society (IHCTAS) CY APR 07-09, 2011 CL Atlanta, GA SP Hand & Composite Tissue Allotransplantat Soc (IHCTAS) ID ORGAN-TRANSPLANT RECIPIENTS; CMV INFECTION; VALGANCICLOVIR PROPHYLAXIS; FACE TRANSPLANTATION; HAND TRANSPLANTATION; PREEMPTIVE THERAPY; DISEASE; STRATEGIES; EFFICACY; GANCICLOVIR AB Face transplantation (FT) is fraught with complications parallel to solid organ transplantation (SOT). As such, donor-related cytomegalovirus (CMV) transmission remains one of the most commonly feared viruses associated with FT. With this in mind, a review of the literature seemed justified, knowing that two of the first four face transplant recipients acquired CMV donor-related viral infection. Although the risk of CMV transmission is acceptable in the setting of SOT, the scenario for those composite tissue allotransplantation (CTA) patients, who are often young and healthy, may be different. Experiences from France and Cleveland have both confirmed suboptimal events related to CMV transmission following transplantation. Therefore, using the information provided here, it is imperative that all FT teams remain aware of these potential risks. Furthermore, all patients pursuing facial CTA should be fully informed as to the risks of donor-related CMV transmission, understand the importance of prophylaxis, and be aware of alternative therapies required to prevent symptomatic disease. C1 [Gordon, C. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg,Dept Surg, Boston, MA 02114 USA. [Gordon, C. R.; Abouhassan, W.] Cleveland Clin, Dept Plast Surg, Inst Dermatol & Plast Surg, Cleveland, OH 44106 USA. [Avery, R. K.] Cleveland Clin, Dept Infect Dis, Inst Med, Cleveland, OH 44106 USA. RP Gordon, CR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg,Dept Surg, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM cgordon5@partners.org NR 49 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 EI 1873-2623 J9 TRANSPL P JI Transplant. Proc. PD NOV PY 2011 VL 43 IS 9 BP 3516 EP 3520 DI 10.1016/j.transproceed.2011.08.043 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 854HL UT WOS:000297485500090 PM 22099832 ER PT J AU Miyazono, S Isayama, T Delori, FC Makino, CL AF Miyazono, Sadaharu Isayama, Tomoki Delori, Francois C. Makino, Clint L. TI Vitamin A activates rhodopsin and sensitizes it to ultraviolet light SO VISUAL NEUROSCIENCE LA English DT Article DE Retinol; Retinal photoreceptors; GPCR; Allosteric regulation; Electrophysiology ID RETINOL-BINDING-PROTEIN; GATED ION CHANNELS; ROD PHOTORECEPTORS; VISUAL-PIGMENT; CONE PHOTORECEPTORS; DARK-ADAPTATION; KNOCKOUT MICE; TIGER SALAMANDER; OPSIN; MEMBRANE AB The visual pigment, rhodopsin, consists of opsin protein with 11-cis retinal chromophore, covalently bound. Light activates rhodopsin by isomerizing the chromophore to the all-trans conformation. The activated rhodopsin sets in motion a biochemical cascade that evokes an electrical response by the photoreceptor. All-trans retinal is eventually released from the opsin and reduced to vitamin A. Rod and cone photoreceptors contain vast amounts of rhodopsin, so after exposure to bright light, the concentration of vitamin A can reach relatively high levels within their outer segments. Since a retinal analog, b-ionone, is capable of activating some types of visual pigments, we tested whether vitamin A might produce a similar effect. In single-cell recordings from isolated dark-adapted salamander green-sensitive rods, exogenously applied vitamin A decreased circulating current and flash sensitivity and accelerated flash response kinetics. These changes resembled those produced by exposure of rods to steady light. Microspectrophotometric measurements showed that vitamin A accumulated in the outer segments and binding of vitamin A to rhodopsin was confirmed in in vitro assays. In addition, vitamin A improved the sensitivity of photoreceptors to ultraviolet ( UV) light. Apparently, the energy of a UV photon absorbed by vitamin A transferred by a radiationless process to the 11-cis retinal chromophore of rhodopsin, which subsequently isomerized. Therefore, our results suggest that vitamin A binds to rhodopsin at an allosteric binding site distinct from the chromophore binding pocket for 11-cis retinal to activate the rhodopsin, and that it serves as a sensitizing chromophore for UV light. C1 [Miyazono, Sadaharu; Isayama, Tomoki; Makino, Clint L.] Harvard Univ, Dept Ophthalmol, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Delori, Francois C.] Harvard Univ, Dept Ophthalmol, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Miyazono, S (reprint author), Harvard Univ, Dept Ophthalmol, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM miyazono@asahikawa-med.ac.jp OI Makino, Clint/0000-0002-6005-9069 FU National Eye Institute [EY011358, EY014104]; Lions of Massachusetts FX We thank Dr. E. R. Makino for helpful advice regarding the in vitro assays, Drs. X.-H. Wen and T. R. Middendorf for insightful discussions, and Dr. A. L. Zimmerman for comments on the manuscript. This research was supported by Award Numbers EY011358 and EY014104 from the National Eye Institute and the Lions of Massachusetts. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Eye Institute or the National Institutes of Health. NR 71 TC 1 Z9 1 U1 0 U2 11 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD NOV PY 2011 VL 28 IS 6 BP 485 EP 497 DI 10.1017/S0952523811000423 PG 13 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 873AN UT WOS:000298853000003 PM 22192505 ER PT J AU Choi, AI Karter, AJ Liu, JY Young, BA Go, AS Schillinger, D AF Choi, Andy I. Karter, Andrew J. Liu, Jennifer Y. Young, Bessie A. Go, Alan S. Schillinger, Dean TI Ethnic Differences in the Development of Albuminuria: The DISTANCE Study SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR-DISEASE; GLYCEMIC CONTROL; POPULATION; ATHEROSCLEROSIS; DISPARITIES; HEALTH; PREVALENCE; MORTALITY AB Objectives: To determine whether ethnic differences in the incidence of albuminuria are present in patients with diabetes, and to identify social, behavioral, and provider factors that explain ethnic differences. Study Design: Survey follow-up design with a race-stratified baseline survey (2005-2006) in diabetic patients from a nonprofit, fully integrated healthcare system in Northern California. We followed the 10,596 respondents (30% whites, 20% blacks, 23% Hispanics, 14% Asians, and 13% Filipinos) without evidence of prevalent albuminuria at baseline. Methods: Incident albuminuria was defined by positive dipstick urinalysis (>= 1) or urine albumin to creatinine level (>= 30 mg/g), and confirmed with repeat testing at least 3 months later. Results: The 27,292 person-years of observation yielded 981 incident albuminuria events. Age-standardized rates of albuminuria (per 1000 person-years) ranged from 13.6 (95% confidence interval [CI] 10.5-17.0) in whites to 27.8 (Cl 18.2-38.3) in blacks. In fully adjusted Cox models, the hazard ratio for blacks (1.22, 95% Cl 1.09-1.38), Asians (1.35, 95% Cl 1.13-1.61), and Filipinos (1.93, 95% Cl 1.61-2.32), but not Hispanics, was significantly greater than it was for whites. In some cases, point estimates changed markedly from the base model when fully adjusted for potential confounders. Moreover, adjustment for an array of potentially mediating factors explained only a small proportion of the observed ethnic disparities. Conclusions: Despite uniform medical care coverage, Filipinos, blacks, and Asians with diabetes developed albuminuria at higher rates than white and Hispanic adults. (Am J Manag Care. 2071;17(11):737-745) C1 [Karter, Andrew J.; Liu, Jennifer Y.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Choi, Andy I.; Schillinger, Dean] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Choi, Andy I.] San Francisco VA Med Ctr, San Francisco, CA USA. [Karter, Andrew J.; Go, Alan S.] Univ Washington, Dept Hlth Serv Res, Seattle, WA 98195 USA. VA Puget Sound Healthcare Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Young, Bessie A.] Univ Washington, Dept Med, Seattle, WA USA. [Schillinger, Dean] Univ Calif San Francisco, San Francisco Gen Hosp, Ctr Vulnerable Populat, San Francisco, CA USA. RP Karter, AJ (reprint author), Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM andy.j.karter@kp.org FU National Institute of Diabetes, Digestive and Kidney Diseases [R01DK081796, RC1 DK086178, R01 DK080726, R01DK65664]; National Institutes of Health [P60 DK20595] FX This work was supported by the National Institute of Diabetes, Digestive and Kidney Diseases (grants R01DK081796, RC1 DK086178, R01 DK080726, and R01DK65664). The Diabetes Research and Training Center was also supported by the National Institutes of Health (grant P60 DK20595). NR 28 TC 2 Z9 2 U1 0 U2 1 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD NOV PY 2011 VL 17 IS 11 BP 737 EP 745 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 854XO UT WOS:000297528300002 PM 22084893 ER PT J AU Adler-Milstein, J DesRoches, CM Jha, AK AF Adler-Milstein, Julia DesRoches, Catherine M. Jha, Ashish K. TI Health Information Exchange Among US Hospitals SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID MEANINGFUL USE; ORGANIZATIONS; PROGRESS; RECORDS AB Objectives: To determine the proportion of US hospitals engaged in health information exchange (HIE) with unaffiliated providers and to identify key hospital-level and market-level factors associated with participating in exchange. Study Design: Using the 2009 American Hospital Association Information Technology survey, supplemented by Dartmouth Atlas, Area Resource File, and other national data, we examined which hospitals participated in regional efforts to electronically exchange clinical data. Methods: We used logistic regression models to determine hospital-level characteristics and market-level characteristics associated with hospitals' likelihood of participating in HIE. Results: We found that 10.7% of US hospitals engaged in HIE with unaffiliated providers. In communities where exchange occurred, for-profit hospitals and those with a small market share were far less likely to engage in HIE than non-profit hospitals or those with a larger market share. Hospitals in more concentrated markets were more likely to exchange and hospitals in markets with higher Medicare spending were less likely to exchange. Conclusions: At the start of implementation of the Health Information Technology for Economic and Clinical Health (HITECH) Act, only a small minority of US hospitals electronically exchange clinical data with unaffiliated providers. Health information exchange is a key part of reforming the healthcare system, and factors related to competitiveness may be holding some providers back. (Am J Manag Care. 2010;17(11):761-768) C1 [Adler-Milstein, Julia] Univ Michigan, Sch Informat, Ann Arbor, MI 48109 USA. [Adler-Milstein, Julia] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [DesRoches, Catherine M.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Harvard Med Sch, Boston Vet Affairs Hosp, 677 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu FU Office of the National Coordinator at the Department of Health and Human Services FX Dr Jha reports consultancies or paid advisory boards from Humedica Scientific Board and has also received grants from the Office of the National Coordinator at the Department of Health and Human Services, which has funded similar work. The other authors (JA-M, CMD) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article. NR 14 TC 34 Z9 34 U1 5 U2 24 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD NOV PY 2011 VL 17 IS 11 BP 761 EP 768 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 854XO UT WOS:000297528300005 PM 22084896 ER PT J AU Kim, H Helmer, DA Zhao, ZL Boockvar, K AF Kim, Hongsoo Helmer, Drew A. Zhao, Zhonglin Boockvar, Kenneth TI Potentially Preventable Hospitalizations Among Older Adults With Diabetes SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID MULTIPLE CHRONIC CONDITIONS; CARE-SENSITIVE CONDITIONS; AVOIDABLE HOSPITALIZATIONS; DISPARITIES; MELLITUS; QUALITY; READMISSIONS; POPULATION; PREVALENCE; INSURANCE AB Objectives: To examine prevalence of and factors associated with different types of potentially preventable hospitalizations (PPHs) among older adults with diabetes. Study Design: Population-based secondary analysis. Methods: We analyzed the California State Inpatient Databases, 2005 to 2006. PPHs for 3 acute and 5 chronic ambulatory care-sensitive conditions relevant for older adults were defined by applying the Prevention Quality Indicator algorithm developed by the Agency for Health Research and Quality. Prevalence and costs of PPHs for acute conditions (acute PPHs) and chronic conditions (chronic PPHs) were examined. Associations of sociodemographic and health-related factors as well as hospitalization history with both types of PPH were estimated. Results: One-fifth of 555,538 hospitalizations of adults 65 years and older with diabetes were PPHs. Of these, 43.7% were acute PPHs and 56.3% were chronic PPHs. The total hospital cost associated with these PPHs was more than $1.1 billion. Having Medi-Cal as the primary payer and hospitalization through the emergency department were positively associated with both types of PPH. Acute PPH rates were lower, but chronic PPH rates were higher, among blacks, patients with multiple chronic conditions, and those with previous admission(s) in the same year. Conclusions: PPHs for common medical conditions are costly and prevalent among older patients with diabetes, suggesting a need for more comprehensive primary care, beyond glycemic control. The groups at risk for acute and chronic PPHs may differ, which suggests that more targeted and tailored approaches are necessary to reduce the rates of each type of PPH. (Am J Manag Care. 2011;17(11):e419-e426) C1 [Kim, Hongsoo] Seoul Natl Univ, Grad Sch Publ Hlth, Seoul 151742, South Korea. [Kim, Hongsoo] Seoul Natl Univ, Inst Hlth & Environm, Seoul 151742, South Korea. [Helmer, Drew A.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Helmer, Drew A.] Baylor Coll Med, Houston, TX 77030 USA. [Zhao, Zhonglin] NYU, Coll Dent, New York, NY USA. [Boockvar, Kenneth] James J Peters VA Med Ctr, Bronx, NY USA. [Boockvar, Kenneth] Mt Sinai Sch Med, New York, NY USA. [Boockvar, Kenneth] Jewish Home Lifecare, New York, NY USA. RP Kim, H (reprint author), Seoul Natl Univ, Grad Sch Publ Hlth, Seoul 151742, South Korea. EM hk65@snu.ac.kr FU Greenwall Foundation FX Dr Boockvar was supported by the Greenwall Foundation. The authors thank the anonymous reviewers for their insightful comments. NR 25 TC 10 Z9 10 U1 0 U2 9 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD NOV PY 2011 VL 17 IS 11 BP E419 EP E426 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 854XO UT WOS:000297528300006 PM 22200058 ER PT J AU Stein, MB Siefert, CJ Stewart, RV Hilsenroth, MJ AF Stein, Michelle B. Siefert, Caleb J. Stewart, Rosemarie Vala Hilsenroth, Mark J. TI Relationship between the Social Cognition and Object Relations Scale (SCORS) and attachment style in a clinical sample SO CLINICAL PSYCHOLOGY & PSYCHOTHERAPY LA English DT Article DE SCORS; Attachment; Object Relations; RQ; ECR-R; Social Cognition ID ADULT ATTACHMENT; RELATIONSHIP SATISFACTION; PERSONALITY-DEVELOPMENT; CLIENT ATTACHMENT; SELF-DISCLOSURE; WORKING MODELS; PSYCHOTHERAPY; PSYCHOPATHOLOGY; THERAPIST; RORSCHACH AB This present study examined the relationship between the Social Cognition and Object Relations Scale (SCORS) and two measures of adult attachment: the Relationship Questionnaire (RQ) and the Experiences in Close Relationships Questionnaire-Revised (ECR-R). Forty-five patients (76% female) at a university-based outpatient treatment clinic participated in this study. We hypothesized that higher levels of attachment security would be associated with higher, more adaptive ratings on the SCORS variables. Results indicated that the SCORS Self-Esteem (SE) variable was significantly positively related to the RQ's Secure Attachment ratings and negatively related with the ECR-R's Anxious Attachment scale. Additionally, negative trends were noted between SE and the RQ's Fearful and Preoccupied Attachment scores. The SCORS Emotional Investments in Relationships and Affective Quality of Representations variables were associated with higher Secure scores and lower, more maladaptive Preoccupied scores on the RQ. It was also associated with greater attachment anxiety as measured by the ECR-R. Using both clinician (SCORS) and participant-rated measures (ECR-R and RQ), this study provides further understanding on how object representations and attachment style relate within a clinical sample. Results are discussed in light of prior research examining relationships between object relations and adult attachments, and clinical implications are also reviewed. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Stein, Michelle B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stein, Michelle B.] Harvard Univ, Sch Med, Psychol Assessment Ctr, Boston, MA 02114 USA. [Siefert, Caleb J.] Univ Michigan, Dearborn, MI 48128 USA. [Stewart, Rosemarie Vala; Hilsenroth, Mark J.] Adelphi Univ, Derner Inst Adv Psychol Studies, Garden City, NY 11530 USA. RP Stein, MB (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq,Suite 701,7th Floor, Boston, MA 02114 USA. EM mstein3@partners.org NR 76 TC 5 Z9 5 U1 2 U2 20 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1063-3995 J9 CLIN PSYCHOL PSYCHOT JI Clin. Psychol. Psychother. PD NOV-DEC PY 2011 VL 18 IS 6 BP 512 EP 523 DI 10.1002/cpp.721 PG 12 WC Psychology, Clinical SC Psychology GA 855GU UT WOS:000297552700007 PM 20806423 ER PT J AU Carpenter, DJ Fong, R Kraus, JE Davies, JT Moore, C Thase, ME AF Carpenter, David J. Fong, Regan Kraus, John E. Davies, John T. Moore, Christine Thase, Michael E. TI Meta-Analysis of Efficacy and Treatment-Emergent Suicidality in Adults by Psychiatric Indication and Age Subgroup Following Initiation of Paroxetine Therapy: A Complete Set of Randomized Placebo-Controlled Trials SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID SEROTONIN REUPTAKE INHIBITORS; NEW-YORK-CITY; ANTIDEPRESSANT TREATMENT; CLINICAL-TRIALS; MAJOR DEPRESSION; RISK; RATES; ADOLESCENTS; ASSOCIATION; PREVENTION AB Objective: This meta-analysis of placebo-controlled paroxetine trials examines suicidality incidence in adults, focusing on disorder and age as potential risk factors. The findings are put in context with an efficacy meta-analysis of the same trial datasets. Data Sources: GlaxoSmithKline paroxetine clinical trial database(s). Study Selection: All double-blind, randomized, placebo-controlled, parallel-group studies of paroxetine therapy in adults enrolling at least 30 patients total were included in the analysis. The dataset comprised 14,911 patients from 61 trials. Data Extraction: Possible cases of suicidality were identified and blindly categorized by an expert panel, using methodology previously used by the US Food and Drug Administration. Incidences of suicidal behavior (preparatory act, suicide attempt, or completed suicide) and any suicidality (suicidal behavior or ideation) were compared between paroxetine and placebo. Efficacy assessments were based on standard depression rating scales (eg, Hamilton Depression Rating Scale or Montgomery-Asberg Depression Rating Scale) and Clinical Global Impressions Improvement scale (CGI-I) scores. Results: In the primary dataset, ie, all disorders combined, there were no significant differences between paroxetine and placebo for overall suicidality (suicidal behavior or ideation: n/n = 83/8,958 [0.93%] vs n/n = 65/5,953 [1.09%], respectively; OR = 0.9 [95% CI, 0.7-1.3]; P = .649) or for suicidal behavior specifically (n/n = 50/8,958 [0.56%] vs n/n = 40/5,953 [0.67%], respectively; OR = 1.2 [95% CI, 0.8-1.9]; P = .483). However, in patients with major depressive disorder (MDD), a greater incidence of suicidal behavior occurred in paroxetine-treated patients than in placebo-treated patients (n/n = 11/3,455 [0.32%] vs n/n = 1/1,978 [0.05%], respectively; OR = 6.7 [95% CI, 1.1-149.4]; P = .058). Across all indications, a higher incidence of suicidal behavior occurred in paroxetine-treated versus placebo-treated adults aged 18 to 24 years (n/n = 17/776 [2.19%] vs n/n = 5/542 [0.92%], respectively; OR = 2.4 [95% CI, 0.9-7.3]). In older age groups, no increase in suicidality was observed. Efficacy was demonstrated in all disorders evaluated, including MDD. Conclusions: Across all disorders, overall suicidality incidence was similar between paroxetine and placebo. However, a higher frequency of suicidal behavior occurred with paroxetine in MDD, which was largely explained by the higher incidence in young adults. These data support the efficacy of paroxetine therapy; however, they also highlight the need for careful monitoring of suicidality during antidepressant therapy, particularly in younger adults. C1 [Fong, Regan] GlaxoSmithKline Inc, Discovery Med, King Of Prussia, PA 19406 USA. [Kraus, John E.] GlaxoSmithKline Inc, Res Triangle Pk, NC USA. [Davies, John T.] GlaxoSmithKline Inc, Harlow, Essex, England. [Moore, Christine] I3 Res, Cary, NC USA. [Thase, Michael E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15260 USA. RP Fong, R (reprint author), GlaxoSmithKline Inc, Discovery Med, 2301 Renaissance Blvd, King Of Prussia, PA 19406 USA. EM Regan.2.fong@GSK.com FU GlaxoSmithKline; Eli Lilly; National Institute of Mental Health; Sepracor; American Psychiatric Publishing; Guilford Publications; Herald House; W. W. Norton Company FX Drs Carpenter, Fong, and Kraus and Mr Davies are employees of and shareholders in GlaxoSmithKline. Dr Moore is an employee of i3 Research; funding for her contribution to this article was provided by GlaxoSmithKline. Dr Thase has been an advisor or consultant to AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest, GlaxoSmithKline, MedAvante, Neuronetics, Novartis, Otsuka, Ortho-McNeil, Pfizer, Schering-Plough, Shire, Supernus, Takeda, and Transcept; has received grant support from Eli Lilly, GlaxoSmithKline, National Institute of Mental Health, and Sepracor; has served on speakers bureaus for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, and Pfizer; has equity holdings in MedAvante; and has received royalties from American Psychiatric Publishing, Guilford Publications, Herald House, and W. W. Norton & Company. Dr Thase's spouse is an employee of Advogent. NR 75 TC 21 Z9 21 U1 4 U2 10 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 NOV PY 2011 VL 72 IS 11 BP 1503 EP 1514 DI 10.4088/JCP.08m04927blu PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 855ME UT WOS:000297567700009 PM 21367354 ER PT J AU Lawson, EA Donoho, DA Blum, JI Meenaghan, EM Misra, M Herzog, DB Sluss, PM Miller, KK Klibanski, A AF Lawson, Elizabeth A. Donoho, Daniel A. Blum, Justine I. Meenaghan, Erinne M. Misra, Madhusmita Herzog, David B. Sluss, Patrick M. Miller, Karen K. Klibanski, Anne TI Decreased Nocturnal Oxytocin Levels in Anorexia Nervosa Are Associated With Low Bone Mineral Density and Fat Mass SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PARAVENTRICULAR NUCLEUS; BULIMIA-NERVOSA; DEFICIENT MICE; CSF OXYTOCIN; WEIGHT-GAIN; FOOD-INTAKE; PEPTIDE-YY; ESTROGEN; RATS; RECEPTOR AB Objective: Anorexia nervosa is characterized by self-induced starvation and associated with severe bone and fat loss. Oxytocin is a peptide hormone involved in appetite and energy homeostasis. Recent data show that oxytocin has an anabolic effect on bone and stimulates osteoblast function. There is limited information about oxytocin levels or their relationship to decreased bone mineral density in anorexia nervosa. Our objective was to investigate the relationship between oxytocin levels, bone mineral density, and body composition in women with anorexia nervosa. Method: We studied 36 women, mean +/- SEM age 27.6 +/- 1.3 years: 17 with DSM-IV anorexia nervosa and 19 healthy controls in a cross-sectional study. Oxytocin levels were determined from pooled serum samples obtained every 20 minutes from 8 PM to RAM during an inpatient overnight visit. Fasting leptin levels were measured. Bone mineral density at the anterior-posterior and lateral spine and hip and body composition were assessed by dual energy x-ray absorptiometry. The study was conducted from September 2004 to June 2008. Results: Subjects with anorexia nervosa versus healthy controls had lower mean SEM oxytocin levels (14.3 +/- 1.5 vs 31.8 +/- 5.1 pg/mL, P = .003), leptin levels (2.7 +/- 0.5 vs 11.4 +/- 1.1 ng/mL, P < .0001), bone mineral density (anterior-posterior spine: 0.83 +/- 0.02 vs 1.04 +/- 0.03; lateral spine: 0.63 +/- 0.02 vs 0.81 +/- 0.02; total hip: 0.79 +/- 0.03 vs 0.97 +/- 0.03 g/cm(2), P < .0001), and fat mass (8.8 +/- 0.6 vs 19.7 +/- 0.9 kg, P < .0001). Oxytocin levels were associated with bone mineral density at the anterior-posterior (r = 0.40, P = .02) and lateral (r = 0.36, P = .04) spine, fat mass (r = 0.42, P = .01), and leptin levels (r = 0.55, P = .001). Conclusions: Overnight secretion of oxytocin in women with anorexia nervosa is decreased compared with healthy women. Low oxytocin levels are associated with decreased bone mineral density and body fat and may contribute to anorexia nervosa induced bone loss. C1 [Lawson, Elizabeth A.; Donoho, Daniel A.; Blum, Justine I.; Meenaghan, Erinne M.; Misra, Madhusmita; Miller, Karen K.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Herzog, David B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sluss, Patrick M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lawson, EA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM ealawson@partners.org FU Bioenvision; National Institutes of Health [M01 RR01066, UL1 RR025758, R01-DK052625]; Harvard/MIT Health Sciences and Technology-Beth Israel Deaconess Medical Center; Pfizer; Merck FX This work was supported in part by an investigator-initiated grant from Bioenvision; National Institutes of Health grants M01 RR01066, UL1 RR025758, and R01-DK052625; and the Clinical Investigator Training Program: Harvard/MIT Health Sciences and Technology-Beth Israel Deaconess Medical Center, in collaboration with Pfizer and Merck. NR 35 TC 37 Z9 38 U1 0 U2 10 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 NOV PY 2011 VL 72 IS 11 BP 1546 EP 1551 DI 10.4088/JCP.10m06617 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 855ME UT WOS:000297567700015 PM 21903023 ER PT J AU Carpenter, DJ Fong, R Kraus, JE Davies, JT Moore, C Thase, ME AF Carpenter, David J. Fong, Regan Kraus, John E. Davies, John T. Moore, Christine Thase, Michael E. TI Odd Odds Reply SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter C1 [Carpenter, David J.; Fong, Regan] GlaxoSmithKline Inc, King Of Prussia, PA USA. [Moore, Christine] I3 Res, Cary, NC USA. [Thase, Michael E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15260 USA. RP Carpenter, DJ (reprint author), GlaxoSmithKline Inc, King Of Prussia, PA USA. EM Regan.2.Fong@gsk.com NR 1 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 72 IS 11 BP 1559 EP 1559 DI 10.4088/JCP.11lr07373a PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 855ME UT WOS:000297567700020 ER PT J AU Finn, KM Heffner, R Chang, YC Bazari, H Hunt, D Pickell, K Berube, R Raju, S Farrell, E Iyasere, C Thompson, R O'Malley, T O'Donnell, W Karson, A AF Finn, Kathleen M. Heffner, Rebecca Chang, Yuchiao Bazari, Hasan Hunt, Daniel Pickell, Karen Berube, Rhodes Raju, Shveta Farrell, Elizabeth Iyasere, Christiana Thompson, Ryan O'Malley, Terrence O'Donnell, Walter Karson, Andrew TI Improving the discharge process by embedding a discharge facilitator in a resident team SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID CARE TRANSITIONS INTERVENTION; HOSPITAL DISCHARGE; PROSPECTIVE PAYMENT; CONTROLLED-TRIAL; PATIENT SAFETY; HEART-FAILURE; CASE MANAGER; FOLLOW-UP; PHYSICIANS; READMISSIONS AB BACKGROUND: Hospital discharges are vulnerable periods for patient safety, especially in teaching hospitals where discharges are done by residents with competing demands. We sought to assess whether embedding a nurse practitioner on a medical team to help physicians with the discharge process would improve communication, patient follow-up, and hospital reutilization. METHODS: A 5-month randomized controlled trial was conducted on the medical service at an academic tertiarycare hospital. A nurse practitioner was randomly assigned to 1 resident team to complete discharge paperwork, arrange follow-up appointments and prescriptions, communicate discharge plans with nursing and primary care physicians, and answer questions from discharged patients. RESULTS: Intervention patients had more discharge summaries completed within 24 hours (67% vs 47%, P < 0.001). Similarly, they had more follow-up appointments scheduled by the time of discharge (62% vs 36%, P < 0.0001) and attended those appointments more often within 2 weeks (36% vs 23%, P < 0.0002). Intervention patients knew whom to call with questions (95% vs 85%, P = 0.003) and were more satisfied with the discharge process (97% vs 76%, P < 0.0001). Attending rounds on the intervention team finished on time (45% vs 31%, P = 0.058), and residents signed out on average 46 minutes earlier each day. There was no significant difference between the groups in 30-day emergency department visits or readmissions. CONCLUSIONS: Helping resident physicians with the discharge process improves many aspects of discharge communication and patient follow-up, and saves residents' time, but had no effect on hospital reutilization for a general medicine population. Journal of Hospital Medicine 2011; 6: 494-500. (C) 2011 Society of Hospital Medicine C1 [Finn, Kathleen M.] Massachusetts Gen Hosp, MGH DOM Clin Educ Program, Dept Med, Boston, MA 02114 USA. [Heffner, Rebecca] Univ Penn, Wharton Sch Business, Philadelphia, PA 19104 USA. [Farrell, Elizabeth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. RP Finn, KM (reprint author), Massachusetts Gen Hosp, MGH DOM Clin Educ Program, Dept Med, 50 Staniford St,Suite 503B, Boston, MA 02114 USA. EM Kfinn@partners.org FU Internal Partners Healthcare Physician Education/Care Delivery Reengineering Innovation Grant FX Funding: Internal Partners Healthcare Physician Education/Care Delivery Reengineering Innovation Grant. The funding source had no role in the design, collection of data, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. NR 30 TC 16 Z9 16 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD NOV-DEC PY 2011 VL 6 IS 9 BP 494 EP 500 DI 10.1002/jhm.924 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 861JM UT WOS:000298015200004 PM 22042739 ER PT J AU Greka, A Mundel, P AF Greka, Anna Mundel, Peter TI Balancing Calcium Signals through TRPC5 and TRPC6 in Podocytes SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; RECEPTOR POTENTIAL CHANNELS; SMOOTH-MUSCLE-CELLS; ANGIOTENSIN-II; NEPHROTIC SYNDROME; CATION CHANNEL; SLIT DIAPHRAGM; ACTIN CYTOSKELETON; KIDNEY PODOCYTES; GLOMERULAR PODOCYTES AB Calcium (Ca(2+)) ions are important mediators of cellular homeostasis owing to their ability to elicit a dynamic, transient, and tightly regulated range of biochemical responses. More than a decade ago, a nonselective, Ca(2+)-permeable, cationic conductance was identified in podocytes downstream of angiotensin II (Ang II) signaling, but its molecular structure remained elusive. Six years ago, transient receptor potential canonical 6 (TRPC6) mutations were found in families with hereditary FSGS, and TRPC5 and TRPC6 channels are now known as the Ca(2+) influx pathways for this previously described, nonselective, cationic current in podocytes. Ang II activation engages this Ca(2+) influx to modulate the actin cytoskeleton in podocytes. These discoveries dovetail with previously described regulation of actin dynamics by the Ca(2+)-activated phosphatase, calcineurin, and the emergence of Rho GTPases as critical regulators of podocyte function in health and disease. Understanding the interconnected signaling regulated by Ca(2+) currents offers potential new therapeutic targets and highlights the notion that synergistic therapies targeting multiple levels of biochemistry may be useful in treating proteinuric kidney disease. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Greka, A (reprint author), Massachusetts Gen Hosp, Div Nephrol, Dept Med, 149 13th St, Charlestown, MA 02129 USA. EM greka.anna@mgh.harvard.edu; mundel.peter@mgh.harvard.edu FU Nephcure Young Investigator Grant; NIH [DK083511, DK57683, DK062472] FX We apologize to our colleagues whose work we were not able to cite in this review because of space limitations. Reviews were often quoted at the expense of original work. We thank D. Corey, W. Kriz, M. Winn, and M.A. Arnaout for helpful discussions. A.G. is funded by a Nephcure Young Investigator Grant and NIH Grant DK083511 and P.M. by NIH Grants DK57683 and DK062472. NR 111 TC 44 Z9 46 U1 0 U2 10 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 NOV PY 2011 VL 22 IS 11 BP 1969 EP 1980 DI 10.1681/ASN.2011040370 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 862ES UT WOS:000298073200005 PM 21980113 ER PT J AU Kanji, Z Powe, CE Wenger, JB Huang, CM Ankers, E Sullivan, DA Collerone, G Powe, NR Tonelli, M Bhan, I Bernhardy, AJ DiBartolo, S Friedman, D Genovese, G Pollak, MR Thadhani, R AF Kanji, Zahra Powe, Camille E. Wenger, Julia B. Huang, Chunmei Ankers, Elizabeth Sullivan, Dorothy A. Collerone, Gina Powe, Neil R. Tonelli, Marcello Bhan, Ishir Bernhardy, Andrea J. DiBartolo, Salvatore Friedman, David Genovese, Giulio Pollak, Martin R. Thadhani, Ravi TI Genetic Variation in APOL1 Associates with Younger Age at Hemodialysis Initiation SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; CHRONIC KIDNEY-DISEASE; AFRICAN-AMERICANS; RACIAL-DIFFERENCES; UNITED-STATES; RISK; MORTALITY; MYH9 AB African Americans have a markedly higher incidence of ESRD compared with other racial groups. Two variants in the APOL1 gene, to date observed only among individuals of recent African ancestry, associate with increased risk for renal disease among African Americans. Here, we investigated whether these risk alleles also associate with age at initiation of chronic hemodialysis. We performed a cross-sectional study of 407 nondiabetic African Americans with ESRD who participated in the Accelerated Mortality on Renal Replacement (ArMORR) study, a prospective cohort of incident chronic hemodialysis patients. African Americans carrying two copies of the G1 risk allele initiated chronic hemodialysis at a mean age of 49.0 +/- 14.9 years, which was significantly younger than both subjects with one copy of the G1 allele (55.9 +/- 16.7 years; P = 0.014) and subjects without either risk allele (61.8 +/- 17.1 years; P = 6.2 x 10(-7)). The association between the presence of the G1 allele and age at initiation of hemodialysis remained statistically significant after adjusting for sociodemographic and other potential confounders. We did not detect an association between the G2 risk allele and age at initiation of hemodialysis, but the sample size was limited. In conclusion, genetic variations in APOL1 identify African Americans that initiate chronic hemodialysis at a younger age. Early interventions to prevent progression of kidney disease may benefit this high-risk population. C1 [Kanji, Zahra; Powe, Camille E.; Wenger, Julia B.; Huang, Chunmei; Ankers, Elizabeth; Sullivan, Dorothy A.; Collerone, Gina; Bhan, Ishir; Thadhani, Ravi] Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. [Powe, Neil R.] Univ Calif San Francisco, Dept Med, San Francisco Gen Hosp, San Francisco, CA 94143 USA. [Tonelli, Marcello] Univ Alberta, Dept Med, Edmonton, AB, Canada. [Bernhardy, Andrea J.; DiBartolo, Salvatore; Friedman, David; Genovese, Giulio; Pollak, Martin R.] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. [Bernhardy, Andrea J.; DiBartolo, Salvatore; Friedman, David; Genovese, Giulio; Pollak, Martin R.] Harvard Univ, Sch Med, Boston, MA USA. [Pollak, Martin R.] Broad Inst Harvard, Cambridge, MA USA. [Pollak, Martin R.] MIT, Cambridge, MA 02139 USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Div Nephrol, Dept Med, Bullfinch 127, Boston, MA 02114 USA. EM thadhani.ravi@mgh.harvard.edu RI Tonelli, Marcello/B-3028-2009 FU National Institutes of Health [NIH DK54931, NIH DK84974]; Abbott FX M.R.P. was supported by National Institutes of Health grant NIH DK54931. R.T. was supported by National Institutes of Health grant NIH DK84974.; R.T. has a research grant from Abbott, and is a consultant to Fresenius Medical Care North America and Shire Human Genetics. NR 17 TC 43 Z9 43 U1 2 U2 6 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2011 VL 22 IS 11 BP 2091 EP 2097 DI 10.1681/ASN.2010121234 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 862ES UT WOS:000298073200017 PM 21997398 ER PT J AU Kimbrel, NA Steffen, LE Meyer, EC Kruse, MI Knight, JA Zimering, RT Gulliver, SB AF Kimbrel, Nathan A. Steffen, Laurie E. Meyer, Eric C. Kruse, Marc I. Knight, Jeffrey A. Zimering, Rose T. Gulliver, Suzy B. TI A Revised Measure of Occupational Stress for Firefighters: Psychometric Properties and Relationship to Posttraumatic Stress Disorder, Depression, and Substance Abuse SO PSYCHOLOGICAL SERVICES LA English DT Article DE firefighters; PTSD; depression; substance abuse ID URBAN FIREFIGHTERS; SCREENING-TEST; PREDICTORS; PARAMEDICS; INVENTORY; SYMPTOMS AB The Sources of Occupational Stress scale (SOOS; Beaton & Murphy, 1993) is a 57-item self-report measure designed to assess the different sources of occupational stress faced by firefighters. The objective of the present research was to develop and evaluate an abbreviated version of the SOOS in order to reduce respondent burden. The revised 14-item version of the SOOS was evaluated in 2 independent samples of firefighters (N = 408) along with measures of job outcomes, posttraumatic stress disorder, depression, and substance abuse. The SOOS-14 exhibited good internal consistency, good factor structure, and good validity coefficients across samples. Although additional studies are needed to replicate and expand on these results, the findings from the present research indicate that the SOOS-14 is a practical, reliable, and valid measure of occupational stress for firefighters. C1 [Kimbrel, Nathan A.; Steffen, Laurie E.; Meyer, Eric C.; Kruse, Marc I.; Gulliver, Suzy B.] Texas A&M Hlth Sci Ctr, Dept Psychiat & Behav Sci, Houston, TX USA. [Knight, Jeffrey A.; Zimering, Rose T.] VA Boston Healthcare Syst, Dept Psychol, Boston, MA USA. [Knight, Jeffrey A.; Zimering, Rose T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Kimbrel, NA (reprint author), VA VISN 17 Ctr Excellence Res Returning War Vet, 4800 Mem Dr 151C, Waco, TX 76711 USA. EM nathan.kimbrel@va.gov RI Kimbrel, Nathan/P-3109-2016 OI Kimbrel, Nathan/0000-0001-7218-1005 NR 32 TC 7 Z9 7 U1 0 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD NOV PY 2011 VL 8 IS 4 BP 294 EP 306 DI 10.1037/a0025845 PG 13 WC Psychology, Clinical SC Psychology GA 854XX UT WOS:000297529200003 ER PT J AU MacMahon, PJ Shelly, MJ Scholz, D Eustace, SJ Kavanagh, EC AF MacMahon, P. J. Shelly, M. J. Scholz, D. Eustace, S. J. Kavanagh, E. C. TI Injectable Corticosteroid Preparations: An Embolic Risk Assessment by Static and Dynamic Microscopic Analysis SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID CERVICAL TRANSFORAMINAL INJECTION; EPIDURAL STEROID INJECTION; SPINAL ARTERY SYNDROME; BENZYL ALCOHOL; VERTEBRAL ARTERY; IN-VITRO; ROOT; RADICULOPATHY; AGGREGATION; PARAPLEGIA AB BACKGROUND AND PURPOSE: Transforaminal CS injections have been associated with severe adverse CNS events, including brain and spinal cord infarction. Our purpose was to describe the static and dynamic microscopic appearances of CS preparations, with an emphasis on their potential to cause adverse central nervous system events by embolic mechanisms during transforaminal injection. MATERIALS AND METHODS: Pharmaceutical preparations of nondilute injectable CSs were used after appropriate mixing: MPA (40 mg/mL), TA (40 mg/mL), and DSP (8 mg/2 mL). For dynamic imaging, a novel methodology was devised to replicate the flow of crystals within spinal cord arterioles. In addition, CS preparations were mixed with plasma to assess for changes in crystal size, morphology, and tendency to aggregate. RESULTS: The CS preparations MPA and TA are composed of crystals of varying sizes. MPA crystal size range was 0.4-26 mu m (mean, 6.94 mu m), TA crystal size range 0.5-110 mu m (mean, 17.4 mu m), and DSP did not contain any significant crystals or particles. There was no change in the crystal morphology or propensity to aggregate after mixing with local anesthetic. After mixing with plasma, the crystals also were unchanged; however, there was a significant reduction in the size of aggregates. On dynamic imaging, these aggregates were proved to maintain their integrity and to act as potential embolization agents. CONCLUSIONS: MPA and TA have a substantial risk of causing infarction by embolization if inadvertently injected intra-arterially at the time of TFESI. DSP is completely soluble and microscopically has no potential to obstruct arterioles. When performing cervical TFESI procedures, the administration of insoluble CSs should be avoided. C1 [MacMahon, P. J.; Shelly, M. J.; Eustace, S. J.; Kavanagh, E. C.] Mater Misericordiae Univ Hosp, Dept Radiol, Dublin, Ireland. [Scholz, D.] Univ Coll, Conway Inst, Dublin, Ireland. RP MacMahon, PJ (reprint author), Massachusetts Gen Hosp, Dept Musculoskeletal Imaging & Intervent, YAW 6030, Boston, MA 02114 USA. EM petermacmahon@yahoo.com NR 37 TC 9 Z9 9 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV PY 2011 VL 32 IS 10 BP 1830 EP 1835 DI 10.3174/ajnr.A2656 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 859PM UT WOS:000297888300013 PM 21940803 ER PT J AU Berkhout, B Jeang, KT AF Berkhout, B. Jeang, K. -T. TI MicroRNAs in viral gene regulation Preface SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Editorial Material C1 [Berkhout, B.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Cambridge, MA 02138 USA. [Berkhout, B.] Univ Amsterdam, NL-1012 WX Amsterdam, Netherlands. [Jeang, K. -T.] NIAID, NIH, Bethesda, MD 20892 USA. [Jeang, K. -T.] MIT, Boston, MA USA. RP Berkhout, B (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Cambridge, MA 02138 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 5 Z9 5 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD NOV-DEC PY 2011 VL 1809 IS 11-12 SI SI BP 587 EP 587 DI 10.1016/j.bbagrm.2011.10.009 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 858WP UT WOS:000297834200001 PM 22055652 ER PT J AU Girard, SL Piche, M Chen, HX Schinn, GW Oh, WY Bouma, BE AF Girard, Simon Lambert Piche, Michel Chen, Hongxin Schinn, Gregory W. Oh, Wang-Yuhl Bouma, Brett E. TI SOA Fiber Ring Lasers: Single-Versus Multiple-Mode Oscillation SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE Fiber laser; nonlinear optical device; optical tuning; semiconductor device noise; semiconductor optical amplifiers ID SEMICONDUCTOR-LASER; LINEWIDTH; AMPLIFIERS AB Earlier investigations have demonstrated that a narrow bandwidth intracavity filter in a semiconductor optical amplifier (SOA) fiber ring laser results in an output spectrum comprising multiple longitudinal modes, whereas a large bandwidth filter generally leads to quasi-single-mode oscillation. In this paper, we report on a numerical model simulating the SOA fiber ring laser dynamics and compare its predictions with experimental results obtained with two different SOAs. We demonstrate that the observed experimental behavior results from the interplay between the complex transfer function of the intracavity optical filter, fast gain saturation and four-wave mixing (FWM) due to the linewidth enhancement factor. The dispersion introduced by the complex transfer function of the filter can lead to modulation instability, which plays a key role in the laser dynamics that can evolve into a single-longitudinal mode (SLM) operation. We also simulate the behavior of the laser emission when the wavelength of the optical filter is finely tuned. C1 [Girard, Simon Lambert; Piche, Michel] Univ Laval, Ctr Opt Photon & Laser, Quebec City, PQ G1V 0A6, Canada. [Chen, Hongxin; Schinn, Gregory W.] EXFO Inc, Quebec City, PQ G1M 2K2, Canada. [Oh, Wang-Yuhl; Bouma, Brett E.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Oh, Wang-Yuhl; Bouma, Brett E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Girard, SL (reprint author), Univ Laval, Ctr Opt Photon & Laser, Quebec City, PQ G1V 0A6, Canada. EM simon.lambert-girard.1@ulaval.ca FU Canadian Institute for Photonic Innovations (CIPI); Natural Sciences and Engineering Research Council of Canada (NSERC); EXFO Inc. FX This work was supported by the Canadian Institute for Photonic Innovations (CIPI), the Natural Sciences and Engineering Research Council of Canada (NSERC), and EXFO Inc. NR 18 TC 10 Z9 10 U1 1 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD NOV-DEC PY 2011 VL 17 IS 6 BP 1513 EP 1520 DI 10.1109/JSTQE.2011.2119294 PG 8 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 859FA UT WOS:000297861000006 ER PT J AU Tian, YJ Rich, BE Vena, N Craig, JM MacConaill, LE Rajaram, V Goldman, S Taha, H Mahmoud, M Ozek, M Sav, A Longtine, JA Lindeman, NI Garraway, LA Ligon, AH Stiles, CD Santagata, S Chan, JA Kieran, MW Ligon, KL AF Tian, Yongji Rich, Benjamin E. Vena, Natalie Craig, Justin M. MacConaill, Laura E. Rajaram, Veena Goldman, Stewart Taha, Hala Mahmoud, Madeha Ozek, Memet Sav, Aydin Longtine, Janina A. Lindeman, Neal I. Garraway, Levi A. Ligon, Azra H. Stiles, Charles D. Santagata, Sandra Chan, Jennifer A. Kieran, Mark W. Ligon, Keith L. TI Detection of KIAA1549-BRAF Fusion Transcripts in Formalin-Fixed Paraffin-Embedded Pediatric Low-Grade Gliomas SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID MAPK PATHWAY ACTIVATION; PILOCYTIC ASTROCYTOMAS; BRAF MUTATION; GENE; DUPLICATION; CANCER AB Alterations of BRAF are the most common known genetic aberrations in pediatric gliomas. They frequently are found in pilocytic astrocytomas, where genomic duplications involving BRAF and the poorly characterized gene KIAA1549 create fusion proteins with constitutive B-Raf kinase activity. BRAF V600E point mutations are less common and generally occur in nonpilocytic tumors. The development of BRAF inhibitors as drugs has created an urgent need for robust clinical assays to identify activating lesions in BRAF. KIAA1549-BRAF fusion transcripts have been detected in frozen tissue, however, methods for FFPE tissue have not been reported. We developed a panel of FFPE-compatible quantitative RT-PCR assays for the most common KIAA1549-BRAF fusion transcripts. Application of these assays to a collection of 51 low-grade pediatric gliomas showed 97% sensitivity and 91% specificity compared with fluorescence in situ hybridization or array comparative genomic hybridization. In parallel, we assayed samples for the presence of the BRAF V600E mutation by PCR pyrosequencing. The data further support previous observations that these two alterations of the BRAF, KIAA1549 fusions and V600E point mutations, are associated primarily with pilocytic astrocytomas and nonpilocytic gliomas, respectively. These results show that fusion transcripts and mutations can be detected reliably in standard FFPE specimens and may be useful for incorporation into future studies of pediatric gliomas in basic science or clinical trials. (J Mal Diagn 2011, 13:669-677; DOI: 10.1016/j.jmoldx.2011.07.002) C1 [Tian, Yongji; Rich, Benjamin E.; Vena, Natalie; Craig, Justin M.; MacConaill, Laura E.; Garraway, Levi A.; Ligon, Azra H.; Ligon, Keith L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Stiles, Charles D.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Kieran, Mark W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Vena, Natalie; Ligon, Azra H.; Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02215 USA. [MacConaill, Laura E.; Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Rajaram, Veena] Childrens Mem Hosp, Dept Pathol & Lab Med, Chicago, IL 60614 USA. [Goldman, Stewart] Childrens Mem Hosp, Div NeuroOncol, Chicago, IL 60614 USA. [Taha, Hala; Mahmoud, Madeha] Childrens Canc Hosp, Dept Pediat Oncol & Pathol, Cairo, Egypt. [Ozek, Memet] Acibadem Univ, Med Ctr, Div Pediat Neurosurg, Istanbul, Turkey. [Sav, Aydin] Acibadem Univ, Med Ctr, Dept Pathol, Istanbul, Turkey. [Longtine, Janina A.; Lindeman, Neal I.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Santagata, Sandra; Chan, Jennifer A.; Ligon, Keith L.] Brigham & Womens Hosp, Div Neuropathol, Boston, MA 02115 USA. [Santagata, Sandra; Ligon, Keith L.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kieran, Mark W.] Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. RP Ligon, KL (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM keith_ligon@dfci.harvard.edu OI Ligon, Keith/0000-0002-7733-600X; Kieran, Mark/0000-0003-2184-7692; sav, aydin/0000-0002-7326-7801 FU Pediatric Low Grade Astrocytoma Foundation FX Supported by the Pediatric Low Grade Astrocytoma Foundation. NR 23 TC 30 Z9 30 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2011 VL 13 IS 6 BP 669 EP 677 DI 10.1016/j.jmoldx.2011.07.002 PG 9 WC Pathology SC Pathology GA 856RZ UT WOS:000297662400010 PM 21884820 ER PT J AU Lebrun, AH Moll-Khosrawi, P Pohl, S Makrypidi, G Storch, S Kilian, D Streichert, T Otto, B Mole, SE Ullrich, K Cotman, S Kohlschutter, A Braulke, T Schulz, A AF Lebrun, Anne-Helene Moll-Khosrawi, Parisa Pohl, Sandra Makrypidi, Georgia Storch, Stephan Kilian, Dirk Streichert, Thomas Otto, Benjamin Mole, Sara E. Ullrich, Kurt Cotman, Susan Kohlschuetter, Alfried Braulke, Thomas Schulz, Angela TI Analysis of Potential Biomarkers and Modifier Genes Affecting the Clinical Course of CLN3 Disease SO MOLECULAR MEDICINE LA English DT Article ID NEURONAL CEROID-LIPOFUSCINOSES; BATTEN-DISEASE; LYSOSOMAL DISORDERS; MOUSE MODEL; EXPRESSION; SPECIFICITY; PHOSPHATASE; PROTEINS; C3G; MITOCHONDRIAL AB Mutations in the CLN3 gene lead to juvenile neuronal ceroid lipofuscinosis, a pediatric neurodegenerative disorder characterized by visual loss, epilepsy and psychomotor deterioration, Although most CLN3 patients carry the same 1-kb deletion in the CLN3 gene, their disease phenotype can be variable. The aims of this study were to (i) study the clinical phenotype in CLN3 patients with identical genotype, (ii) identify genes that are dysregulated in CLN3 disease regardless of the clinical course that could be useful as biomarkers, and (iii) find modifier genes that affect the progression rate of the disease. A total of 25 CLN3 patients homozygous for the 1-kb deletion were classified into groups with rapid, average or slow disease progression using an established clinical scoring system. Genome-wide expression profiling was performed in eight CLN3 patients with different disease progression and matched controls. The study showed high phenotype variability in CLN3 patients. Five genes were dysregulated in all CLN3 patients and present candidate biomarkers of the disease. Of those, dual specificity phosphatase 2 (DUSP2) was also validated in acutely CLN3-depleted cell models and in CbCln3(Delta ex7/8) cerebellar precursor cells. A total of 13 genes were upregulated in patients with rapid disease progression and downregulated in patients with slow disease progression; one gene showed dysregulation in the opposite way. Among these potential modifier genes, guanine nucleotide exchange factor 1 for small GTPases of the Ras family (RAPGEF1) and transcription factor Spi-B (SPIB) were validated in an acutely CLN3-depleted cell model. These findings indicate that differential perturbations of distinct signaling pathways might alter disease progression and provide insight into the molecular alterations underlying neuronal dysfunction in CLN3 disease and neurodegeneration in general. (C) 2011 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.molmed.org doi: 10.2119/molmed.2010.00241 C1 [Lebrun, Anne-Helene; Moll-Khosrawi, Parisa; Pohl, Sandra; Makrypidi, Georgia; Storch, Stephan; Kilian, Dirk; Ullrich, Kurt; Kohlschuetter, Alfried; Braulke, Thomas; Schulz, Angela] Univ Med Ctr Hamburg Eppendorf, Childrens Hosp, D-20246 Hamburg, Germany. [Streichert, Thomas; Otto, Benjamin] Univ Med Ctr Hamburg Eppendorf, Array Serv Ctr, D-20246 Hamburg, Germany. [Mole, Sara E.] UCL, Med Res Council Lab Mol Cell Biol, Mol Med Unit, UCL Inst Child Hlth, London, England. [Mole, Sara E.] UCL, Dept Genet Evolut & Environm, London, England. [Cotman, Susan] Massachusetts Gen Hosp, Ctr Human Genet, Boston, MA 02114 USA. RP Schulz, A (reprint author), Univ Med Ctr Hamburg Eppendorf, Childrens Hosp, Martinistr 52, D-20246 Hamburg, Germany. EM an.schulz@uke.de OI Mole, Sara/0000-0003-4385-4957 FU Deutsche Forschungsgemeinschaft [SCHU1597/2-1]; Nachstenliebe e.V.; NCL-Gruppe Deutschland e.V. FX We thank the affected and control families for participating in this study and Johannes Brand for technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft (grant SCHU1597/2-1) and the parent organizations Nachstenliebe e.V. and NCL-Gruppe Deutschland e.V. NR 35 TC 15 Z9 15 U1 0 U2 4 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD NOV-DEC PY 2011 VL 17 IS 11-12 BP 1253 EP 1261 DI 10.2119/molmed.2010.00241 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 860OY UT WOS:000297958800016 PM 21863212 ER PT J AU Odierna, DH Afable-Munsuz, A Ikediobi, O Beattie, M Knight, S Ko, M Wilson, A Ponce, NA AF Odierna, Donna H. Afable-Munsuz, Aimee Ikediobi, Ogechi Beattie, Mary Knight, Sara Ko, Michelle Wilson, Adrienne Ponce, Ninez A. TI Early developments in gene-expression profiling of breast tumors: potential for increasing black-white patient disparities in breast cancer outcomes? SO PERSONALIZED MEDICINE LA English DT Article DE African-American women; breast cancer mortality; gene-expression profiling; personalized medicine; racial disparities; social determinants of health ID POLYMERASE-CHAIN-REACTION; CORE BIOPSY-TISSUE; SOCIOECONOMIC-STATUS; AFRICAN-AMERICAN; PROGNOSTIC ROLE; UNITED-STATES; ONCOTYPE DX; SURVIVAL; WOMEN; STAGE AB New prognostic tests, such as gene-expression profiling (GEP) of breast tumors, are expected to prolong survival and improve the quality of life for many breast cancer patients. In this article, we argue that GEP has not been adequately validated in minority populations, and that both biological and social factors might affect the broad utility of these tests in diverse populations. We suggest that the widespread use of this technology could potentially lead to suboptimal treatment for black women, resulting in a further increase in black-white patient disparities in treatment response, morbidity and mortality rates. We argue for the need to build a large and diverse evidence base for GEP and other emerging technologies in personalized medicine. C1 [Odierna, Donna H.; Afable-Munsuz, Aimee] SUNY Downstate Sch Publ Hlth, Dept Community Hlth Sci, Brooklyn, NY 11203 USA. [Odierna, Donna H.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco Branch, UC Cochrane Ctr, San Francisco, CA 94118 USA. [Beattie, Mary; Wilson, Adrienne] Univ Calif San Francisco, Div Gen Internal Med, UCSF Canc Risk Program, San Francisco, CA 94143 USA. [Knight, Sara] Univ Calif San Francisco, Hlth Serv Res & Dev Serv, San Francisco Vet Affairs Med Ctr, Dept Psychiat, San Francisco, CA 94143 USA. [Knight, Sara] Univ Calif San Francisco, Hlth Serv Res & Dev Serv, San Francisco Vet Affairs Med Ctr, Dept Urol, San Francisco, CA 94143 USA. [Ko, Michelle; Ponce, Ninez A.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90095 USA. RP Odierna, DH (reprint author), Univ Calif San Francisco, Dept Clin Pharm, San Francisco Branch, UC Cochrane Ctr, 3333 Calif St,Box 0613, San Francisco, CA 94118 USA. EM Donna.Odierna@ucsf.edu OI Odierna, Donna H/0000-0003-4156-1456; Ponce, Ninez/0000-0001-5151-6718 FU UCSF Center for Translational and Policy Research on Personalized Medicine (TRANSPERS), National Cancer Institute (NCI) [P01 CA130818-02A1, P01 CA 130818]; UCSF Clinical and Translational Science Institute, NIH/NCRR UCSF-CTSI [UL-1 RR024131]; Health Services Research and Development, Interdisciplinary Program [IIR 09-135]; UCSF [NCI 2P50 058207]; Avon Foundation; CSF Center for Clinical and Translational Research; Flight Attendant Medical Research Foundation FX The study was supported by the UCSF Center for Translational and Policy Research on Personalized Medicine (TRANSPERS P01 CA130818-02A1) National Cancer Institute (NCI) P01 CA 130818 (principal investigator: K Phillips). The study was also supported by the UCSF Clinical and Translational Science Institute, NIH/NCRR UCSF-CTSI Grant Number UL-1 RR024131. Health Services Research and Development, Interdisciplinary Program to Improve Health Care for Veterans with Complex Comorbid Conditions and Health Services Research and Development Investigator Initiated Award (IIR 09-135). Mary Beattie is also funded by the UCSF Breast Specialized Program of Research Excellence (SPORE NCI 2P50 058207) and the Avon Foundation. Adrienne Wilson is funded by the Avon Foundation. Donna H Odierna is funded by the UCSF Center for Clinical and Translational Research and the Flight Attendant Medical Research Foundation. Sara Knight is employed by the Health Services Research and Development Service San Francisco Veterans Affairs Medical Center. This paper is the responsibility of the authors and the perspectives expressed within do not necessarily reflect the views of the Department of Veterans Affairs. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 84 TC 2 Z9 2 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD NOV PY 2011 VL 8 IS 6 BP 669 EP 679 DI 10.2217/PME.11.67 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 853ZI UT WOS:000297463800016 PM 22190978 ER PT J AU Greene, ER Huang, S Serhan, CN Panigrahy, D AF Greene, Emily R. Huang, Sui Serhan, Charles N. Panigrahy, Dipak TI Regulation of inflammation in cancer by eicosanoids SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Review DE Eicosanoids; Inflammation; Cancer; Metastasis; Tumor microenvironment ID SOLUBLE EPOXIDE HYDROLASE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; 15-HYDROXYPROSTAGLANDIN DEHYDROGENASE EXPRESSION; SUPPRESSES TUMOR-GROWTH; HUMAN COLORECTAL-CANCER; ARACHIDONIC-ACID; CELL-PROLIFERATION; BREAST-CANCER; COLON-CANCER; EPOXYEICOSATRIENOIC ACIDS AB Inflammation in the tumor microenvironment is now recognized as one of the hallmarks of cancer. Endogenously produced lipid autacoids, locally acting small molecule lipid mediators, play a central role in inflammation and tissue homeostasis, and have recently been implicated in cancer. A well-studied group of autacoid mediators that are the products of arachidonic acid metabolism include: the prostaglandins, leukotrienes, lipoxins and cytochrome P450 (CYP) derived bioactive products. These lipid mediators are collectively referred to as eicosanoids and are generated by distinct enzymatic systems initiated by cyclooxygenases (COX 1 and 2), lipoxygenases (5-LOX, 12-LOX, 15-LOXa, 15-LOXb), and cytochrome P450s, respectively. These pathways are the target of approved drugs for the treatment of inflammation, pain, asthma, allergies, and cardiovascular disorders. Beyond their potent anti-inflammatory and anti-cancer effects, non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 specific inhibitors have been evaluated in both preclinical tumor models and clinical trials. Eicosanoid biosynthesis and actions can also be directly influenced by nutrients in the diet, as evidenced by the emerging role of omega-3 fatty acids in cancer prevention and treatment. Most research dedicated to using eicosanoids to inhibit tumor-associated inflammation has focused on the COX and LOX pathways. Novel experimental approaches that demonstrate the anti-tumor effects of inhibiting cancer-associated inflammation currently include: eicosanoid receptor antagonism, overexpression of eicosanoid metabolizing enzymes, and the use of endogenous anti-inflammatory lipid mediators. Here we review the actions of eicosanoids on inflammation in the context of tumorigenesis. Eicosanoids may represent a missing link between inflammation and cancer and thus could serve as therapeutic target(s) for inhibiting tumor growth. (C) 2011 Elsevier Inc. All rights reserved. C1 [Greene, Emily R.; Panigrahy, Dipak] Harvard Univ, Sch Med, Childrens Hosp Boston, Vasc Biol Program, Boston, MA 02115 USA. [Greene, Emily R.; Panigrahy, Dipak] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. [Huang, Sui] Univ Calgary, Inst Biocomplex & Informat, Calgary, AB, Canada. [Serhan, Charles N.] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. RP Panigrahy, D (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Vasc Biol Program, Boston, MA 02115 USA. EM emily.greene@childrens.harvard.edu; sui.huang@ucalgary.ca; cnserhan@zeus.bwh.harvard.edu; dipak.panigrahy@childrens.harvard.edu FU National Cancer Institute [RO1CA148633-01A1] FX We thank Aria Kaipainen and Gabrielle Fredman for suggestions in preparing the manuscript; Danielle Stanton for preparation of the figure. This work was supported by National Cancer Institute grant RO1CA148633-O1A1 (DP). NR 183 TC 89 Z9 91 U1 2 U2 41 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-8823 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD NOV PY 2011 VL 96 IS 1-4 SI SI BP 27 EP 36 DI 10.1016/j.prostaglandins.2011.08.004 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 860RC UT WOS:000297964400006 PM 21864702 ER PT J AU Garzon, B Emblem, KE Mouridsen, K Nedregaard, B Due-Tonnessen, P Nome, T Hald, JK Bjornerud, A Haberg, AK Kvinnsland, Y AF Garzon, Benjamin Emblem, Kyrre E. Mouridsen, Kim Nedregaard, Beard Due-Tonnessen, Pauline Nome, Terje Hald, John K. Bjornerud, Atle Haberg, Asta K. Kvinnsland, Yngve TI Multiparametric analysis of magnetic resonance images for glioma grading and patient survival time prediction SO ACTA RADIOLOGICA LA English DT Article DE MR imaging; perfusion; brain; primary neoplasms ID CEREBRAL BLOOD-VOLUME; HISTOGRAM ANALYSIS; TUMOR GRADE; MR; OLIGODENDROGLIOMAS; PROGRESSION; MANAGEMENT; MAPS AB Background: A systematic comparison of magnetic resonance imaging (MRI) options for glioma diagnosis is lacking. Purpose: To investigate multiple MR-derived image features with respect to diagnostic accuracy in tumor grading and survival prediction in glioma patients. Material and Methods: T1 pre- and post-contrast, T2 and dynamic susceptibility contrast scans of 74 glioma patients with histologically confirmed grade were acquired. For each patient, a set of statistical features was obtained from the parametric maps derived from the original images, in a region-of-interest encompassing the tumor volume. A forward stepwise selection procedure was used to find the best combinations of features for grade prediction with a cross-validated logistic model and survival time prediction with a cox proportional-hazards regression. Results: Presence/absence of enhancement paired with kurtosis of the FM (first moment of the first-pass curve) was the feature combination that best predicted tumor grade (grade II vs. grade III-IV; median AUC = 0.96), with the main contribution being due to the first of the features. A lower predictive value (median AUC = 0.82) was obtained when grade IV tumors were excluded. Presence/absence of enhancement alone was the best predictor for survival time, and the regression was significant (P < 0.0001). Conclusion: Presence/absence of enhancement, reflecting transendothelial leakage, was the feature with highest predictive value for grade and survival time in glioma patients. C1 [Garzon, Benjamin; Haberg, Asta K.] NTNU, Dept Circulat & Med Imaging, Trondheim, Norway. [Emblem, Kyrre E.; Bjornerud, Atle] Oslo Univ Hosp, Rikshosp, Intervent Ctr, Oslo, Norway. [Emblem, Kyrre E.] Massachusetts Gen Hosp, Dept Radiol, MGH HST AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Emblem, Kyrre E.] Harvard Univ, Sch Med, Boston, MA USA. [Mouridsen, Kim] Aarhus Univ, Ctr Functionally Integrat Neurosci, Aarhus, Denmark. [Nedregaard, Beard; Due-Tonnessen, Pauline; Nome, Terje; Hald, John K.] Oslo Univ Hosp, Rikshosp, Dept Radiol & Nucl Med, Oslo, Norway. [Haberg, Asta K.] St Olavs Hosp, Dept Med Imaging, Trondheim, Norway. [Kvinnsland, Yngve] NordicImagingLab, Bergen, Norway. RP Garzon, B (reprint author), NTNU, Dept Circulat & Med Imaging, Trondheim, Norway. EM benjamin.garzon@ntnu.no RI Emblem, Kyrre/H-6691-2012; OI Emblem, Kyrre/0000-0002-6580-9519; Garzon, Benjamin/0000-0002-4647-7280 FU Rikshospitalet, Oslo University Hospital (Oslo, Norway) FX We thank David Scheie, from Rikshospitalet, Oslo University Hospital (Oslo, Norway), for contributions to this work. NR 34 TC 7 Z9 8 U1 0 U2 11 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0284-1851 J9 ACTA RADIOL JI Acta Radiol. PD NOV PY 2011 VL 52 IS 9 BP 1052 EP 1060 DI 10.1258/ar.2011.100510 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 854IW UT WOS:000297489200020 PM 21969702 ER PT J AU Healy, JM Patel, T Lee, S Sanchez-Reilly, S AF Healy, Jennifer M. Patel, Taral Lee, Shuko Sanchez-Reilly, Sandra TI Do Symptoms Matter When Considering Patients for Phase I Clinical Trials? A Pilot Study of Older Adults With Advanced Cancer SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE phase I; palliative care; symptoms; quality of life; older adults ID COOPERATIVE-ONCOLOGY-GROUP; PROGNOSTIC-FACTORS; BREAST-CANCER; CHEMOTHERAPY; TOXICITY; SURVIVAL; BENEFITS; CRITERIA; AGE AB Older adults (OA) with advanced cancer (AC) undergoing phase 1 clinical trials (PICT) have poor prognosis. There are no studies which describe symptoms experienced by OA. Methods: Retrospective chart review of PICT participants > 60 years. OA were compared by age (> 65 vs 60-65) and by number of symptoms (> 3 vs <= 3). Results: N = 56. Mean age = 67.09; 48.21% female. Median life-expectancy = 5 months (interquartile range = 2-9 months); 80.36% had pain; of those 64% without pain scale. Most did not have interdisciplinary professionals or hospice referrals. Older adults with > 3 symptoms had more admissions (37.5% vs 14.29%; P = .0335), complications (46.43% vs 16.07%; P = .0026), and greater decline in functional status (24 participants > 3 symptoms vs 8; P = .0173). There were no significant differences comparing OA by age. Conclusions: Older adults enrolled in PICT with more symptoms may sacrifice QOL for experimental treatment. C1 [Healy, Jennifer M.; Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Geriatr Gerontol & Palliat Care, San Antonio, TX 78229 USA. [Patel, Taral; Lee, Shuko; Sanchez-Reilly, Sandra] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Healy, JM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Geriatr Gerontol & Palliat Care, 7703 Floyd Curl Dr,MC 7875, San Antonio, TX 78229 USA. EM Healyj@uthscsa.edu NR 18 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2011 VL 28 IS 7 BP 463 EP 466 DI 10.1177/1049909111400723 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 854IA UT WOS:000297487000002 PM 21398266 ER PT J AU Zimmerman, K Rudolph, J Salow, M Skarf, LM AF Zimmerman, Kristin Rudolph, James Salow, Marci Skarf, L. Michal TI Delirium in Palliative Care Patients: Focus on Pharmacotherapy SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Review DE delirium; palliative care; assessment; pharmacotherapy; symptom management; anticholinergic ID SERUM ANTICHOLINERGIC ACTIVITY; ILL CANCER-PATIENTS; ELDERLY-PATIENTS; ASSESSMENT SCALE; TERMINAL CANCER; PREDICTION RULE; COMPLICATIONS; MEDICATIONS; HYDRATION; ASSOCIATION AB Patients receiving palliative care often possess multiple risk factors and predisposing conditions for delirium. The impact of delirium on patient care in this population may also be far-reaching: affecting not only quality of remaining life but the dying process experienced by patients, caregivers, and the medical team as well. As palliative care focuses on comfort and symptom management, the approach to assessment and subsequent treatment of delirium in palliative care patients may prove difficult for providers to navigate. This article summarizes the multifactorial nature, numerous predisposing medical risk factors, neuropsychiatric adverse effects of palliative medications, pharmacokinetic changes, and challenges complicating delirium assessment and provides a systematic framework for assessment. The benefits, risks, and patient-specific considerations for treatment selection are also discussed. C1 [Zimmerman, Kristin; Rudolph, James; Salow, Marci; Skarf, L. Michal] VA Boston Healthcare Syst, Dept Pharm, Boston, MA USA. [Zimmerman, Kristin; Rudolph, James; Salow, Marci; Skarf, L. Michal] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Zimmerman, Kristin; Rudolph, James; Salow, Marci; Skarf, L. Michal] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. RP Zimmerman, K (reprint author), VA Boston Healthcare Syst, Dept Pharm, 940 Belmont St,119, Brockton, MA 02301 USA. EM Zimmerman.Kristin@gmail.com NR 74 TC 5 Z9 5 U1 0 U2 3 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 NOV PY 2011 VL 28 IS 7 BP 501 EP 510 DI 10.1177/1049909111403732 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 854IA UT WOS:000297487000008 PM 21454319 ER PT J AU Tranah, GJ Blackwell, T Stone, KL Ancoli-Israel, S Paudel, ML Ensrud, KE Cauley, JA Redline, S Hillier, TA Cummings, SR Yaffe, K AF Tranah, Gregory J. Blackwell, Terri Stone, Katie L. Ancoli-Israel, Sonia Paudel, Misti L. Ensrud, Kristine E. Cauley, Jane A. Redline, Susan Hillier, Teresa A. Cummings, Steven R. Yaffe, Kristine CA SOF Res Grp TI Circadian activity rhythms and risk of incident dementia and mild cognitive impairment in older women SO ANNALS OF NEUROLOGY LA English DT Article ID NURSING-HOME PATIENTS; SLEEP-WAKE PATTERNS; AGE-RELATED-CHANGES; CONSTANT DIM LIGHT; ALZHEIMERS-DISEASE; SUPRACHIASMATIC NUCLEUS; OSTEOPOROTIC FRACTURES; LOCUS-COERULEUS; WRIST ACTIVITY; OREXIN AB Objective: Previous cross-sectional studies have observed alterations in activity rhythms in dementia patients but the direction of causation is unclear. We determined whether circadian activity rhythms measured in community-dwelling older women are prospectively associated with incident dementia or mild cognitive impairment (MCI). C1 [Tranah, Gregory J.] UCSF, San Francisco Coordinating Ctr, Calif Pacific Med Ctr Res Inst, San Francisco, CA 94107 USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Paudel, Misti L.; Ensrud, Kristine E.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Redline, Susan] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Hillier, Teresa A.] Kaiser Permanente Ctr Hlth Res NW Hawaii, Portland, OR USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94107 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94107 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94107 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Tranah, GJ (reprint author), UCSF, San Francisco Coordinating Ctr, Calif Pacific Med Ctr Res Inst, 185 Berry St,Lobby 4,Suite 5700, San Francisco, CA 94107 USA. EM gtranah@sfcc-cpmc.net OI Cauley, Jane A/0000-0003-0752-4408 FU National Institutes of Health [AG05407/NIA, AR35582/NIAMS, AG05394/NIA, AR35583/NIAMS, AG005 407/NIA, AG027576-22/NIA, AG00539422A1, AG08415/NIA, AG030474/NIA, AG027574-22A1/NIA, AG026 720/NIA]; National Institute of Aging [K24 AG031155/NIA]; Novartis Pharmaceuticals; NIA; NIH; Alzheimer Association; DOD; AHAF; California Pacific Medical Center; Roche Molecular Systems; Sepracor and Litbebook, Inc.; NIAMSD FX The Study of Osteoporotic Fractures (SOF) and SOF-WISE is supported by the National Institutes of Health funding (AG05407/NIA/S.R.C., AR35582/NIAMS/J.A.C., AG05394/NIA/K.E.E., AR35583/NIAMS/S.A-I., AG005 407/NIA/S.R.C., AG027576-22/NIA/J.A.C., AG00539422A1/NIA/K.E.E., AG08415/NIA/S.A-I., AG030474/NIA/G.J.T., AG027574-22A1/NIA/J.A.C., and AG026 720/NIA/K.L.S.). Dr Kristine Yaffe is supported in part by the National Institute of Aging grant K24 AG031155/NIA/K.Y. and an Independent Investigator Award from the Alzheimer's Association.; J.A.C. receives research funding and consulting fees from Novartis Pharmaceuticals. K.Y. has received a grant from the NIA; has been a board member at Pfizer, Medivation, NIMH, and Beeson Scientific Advisory; has grants/grants pending from the NIH, Alzheimer Association, DOD, and AHAF; has received travel/accommodations/meeting expenses from the Alzheimer Association, NIH, Beeson, Japan Geriatrics Society, Wake Forest University, and State of California DHS. K.E.E. has received a grant from the NIA; is a federal employee of the Veterans Affairs Medical Center in Minneapolis, MN; and has received research support from California Pacific Medical Center, which receives funding from Roche Molecular Systems. S.R.C., K.L.S., T.B., and G.J.T. are employees of the California Pacific Medical Center and receive research support from Roche Molecular Systems. T.B., J.A.C., G.J.T., and K.L.S. have received a grant from the NIH. S.A.-I. has received a grant from the NIH; has received grants from Sepracor and Litbebook, Inc.; has served as an advisor or consultant to Ferring Pharmaceuticals, Inc., GlaxoSmithKline, Merck, NeuroVigil, Inc., Neurocrine Biosciences, Pfizer, Philips Respironics, sanofi-aventis, Sepracor, Inc., Schering-Plough, and Purdue Pharma LP. T.H. has received grants from the NIH (from the NIAMSD and the NIA). S.R. has been under subcontract from the NIH via California Pacific and is also a recipient of an endowed professorship at Harvard Medical School, donated by Dr. Peter C. Farrell, the CEO of RosMed, Inc. NR 94 TC 99 Z9 100 U1 7 U2 22 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2011 VL 70 IS 5 BP 722 EP 732 DI 10.1002/ana.22468 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 857TB UT WOS:000297741600009 PM 22162057 ER PT J AU Mainero, C Boshyan, J Hadjikhani, N AF Mainero, Caterina Boshyan, Jasmine Hadjikhani, Nouchine TI Altered functional magnetic resonance imaging resting-state connectivity in periaqueductal gray networks in migraine SO ANNALS OF NEUROLOGY LA English DT Article ID VOXEL-BASED MORPHOMETRY; BRAIN-STEM ACTIVATION; GREY-MATTER CHANGES; CUTANEOUS ALLODYNIA; CORTICAL HYPEREXCITABILITY; HEADACHE; PAIN; CORTEX; STIMULATION; ABNORMALITIES AB Objective: The periaqueductal gray matter (PAG), a known modulator of somatic pain transmission, shows evidence of interictal functional and structural abnormalities in migraineurs, which may contribute to hyperexcitability along spinal and trigeminal nociceptive pathways, and lead to the migraine attack. The aim of this study was to examine functional connectivity of the PAG in migraine. C1 [Mainero, Caterina; Boshyan, Jasmine; Hadjikhani, Nouchine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Hadjikhani, Nouchine] Swiss Fed Inst Technol, Brain Mind Inst, CH-1015 Lausanne, Switzerland. RP Hadjikhani, N (reprint author), Martinos Ctr Biomed Imaging, Bldg149,13th St,Room 2301, Charlestown, MA 02129 USA. EM nouchine@nmr.mgh.harvard.edu RI Hadjikhani, Nouchine/C-2018-2008 OI Hadjikhani, Nouchine/0000-0003-4075-3106 FU NIH, National Institute of Neurological Disorders and Stroke (NINDS) [5P01 NS 35611-09] FX This work was supported by NIH, National Institute of Neurological Disorders and Stroke (NINDS) grant 5P01 NS 35611-09. NR 42 TC 103 Z9 115 U1 1 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2011 VL 70 IS 5 BP 838 EP 845 DI 10.1002/ana.22537 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 857TB UT WOS:000297741600018 PM 22162064 ER PT J AU Foster, MC Yang, Q Hwang, SJ Hoffmann, U Fox, CS AF Foster, Meredith C. Yang, Qiong Hwang, Shih-Jen Hoffmann, Udo Fox, Caroline S. TI Heritability and genome-wide association analysis of renal sinus fat accumulation in the Framingham Heart Study SO BMC MEDICAL GENETICS LA English DT Article ID BODY-MASS INDEX; CHRONIC KIDNEY-DISEASE; METABOLIC SYNDROME; RISK; CKD; CIRCUMFERENCE; LIPODYSTROPHY; LINKAGE; OBESITY; VARIANT AB Background: Ectopic fat accumulation in the renal sinus is associated with chronic kidney disease and hypertension. The genetic contributions to renal sinus fat accumulation in humans have not been well characterized. Methods: The present analysis consists of participants from the Framingham Offspring and Third Generation who underwent computed tomography; renal sinus fat and visceral adipose tissue (VAT) were quantified. Renal sinus fat was natural log transformed and sex- and cohort-specific residuals were created, adjusted for (1) age, (2) age and body mass index (BMI), and (3) age and VAT. Residuals were pooled and used to calculate heritability using variance-components analysis in SOLAR. A genome-wide association study (GWAS) for renal sinus fat was performed using an additive model with approximately 2.5 million imputed single nucleotide polymorphisms (SNPs). Finally, we identified the associations of renal sinus fat in our GWAS results with validated SNPs for renal function (n = 16), BMI (n = 32), and waist-to-hip ratio (WHR, n = 14), and applied a multi-SNP genetic risk score method to determine if the SNPs for each renal and obesity trait were in aggregate associated with renal sinus fat. Results: The heritability of renal sinus fat was 39% (p < 0.0001); results were not materially different after adjustment for BMI (39%) or VAT (40%). No SNPs reached genome-wide significance in our GWAS. In our candidate gene analysis, we observed nominal, direction consistent associations with renal sinus fat for one SNP associated with renal function (p = 0.01), two associated with BMI (p < 0.03), and two associated with WHR (p < 0.03); however, none remained significant after accounting for multiple testing. Finally, we observed that in aggregate, the 32 SNPs associated with BMI were nominally associated with renal sinus fat (multi-SNP genetic risk score p = 0.03). Conclusions: Renal sinus fat is a heritable trait, even after accounting for generalized and abdominal adiposity. This provides support for further research into the genetic determinants of renal sinus fat. While our study was underpowered to detect genome-wide significant loci, our candidate gene BMI risk score results suggest that variability in renal sinus fat may be associated with SNPs previously known to be associated with generalized adiposity. C1 [Foster, Meredith C.; Hwang, Shih-Jen; Fox, Caroline S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA 01702 USA. [Foster, Meredith C.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA. [Foster, Meredith C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA. RP Fox, CS (reprint author), Natl Heart Lung & Blood Inst Framingham Heart Stu, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov RI Yang, Qiong/G-5438-2014 FU National Heart, Lung and Blood Institute [N01-HC-25195] FX We would like to acknowledge and thank Toby Johnson for sharing his method for creating the multi-SNP genetic risk score test statistic. The Framingham Heart Study is supported by the National Heart, Lung and Blood Institute (N01-HC-25195). The funding body did not play a role in the study design, collection, analysis, and interpretation of data, in the writing of the manuscript, or the decision to submit the manuscript for publication. NR 33 TC 3 Z9 3 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD NOV 1 PY 2011 VL 12 AR 148 DI 10.1186/1471-2350-12-148 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 856UT UT WOS:000297669900001 PM 22044751 ER PT J AU Mintzer, J O'Neill, C AF Mintzer, Jacobo O'Neill, Courtney TI Depression in Alzheimer's disease: consequence or contributing factor? SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Editorial Material DE Alzheimer's disease; cognitive impairment; dementia; depression ID SERTRALINE; CRITERIA C1 [Mintzer, Jacobo] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [O'Neill, Courtney] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. RP Mintzer, J (reprint author), Ralph H Johnson VA Med Ctr, Charleston, SC USA. EM mintzerj@musc.edu FU NIMH NIH HHS [U01MH066136] NR 10 TC 1 Z9 1 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 EI 1744-8360 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD NOV PY 2011 VL 11 IS 11 BP 1501 EP 1503 DI 10.1586/ERN.11.145 PG 3 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 856HP UT WOS:000297629900001 PM 22014127 ER PT J AU Jiang, BN Struthers, A Sun, Z Feng, Z Zhao, XQ Zhao, KY Dai, WZ Zhou, XB Berens, ME Zhang, L AF Jiang, Beini Struthers, Allan Sun, Zhe Feng, Zhuo Zhao, Xuqian Zhao, Kaiyong Dai, Weizhong Zhou, Xiaobo Berens, Michael E. Zhang, Le TI Employing graphics processing unit technology, alternating direction implicit method and domain decomposition to speed up the numerical diffusion solver for the biomedical engineering research SO INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING LA English DT Article DE graphics processing unit (GPU); alternating direction implicit method (ADI); parallel computing; domain decomposition ID CYLINDRICAL SKIN-STRUCTURE; BRAIN-TUMORS; PRECONDITIONED RICHARDSON; MULTICELLULAR PATTERNS; MULTISCALE; MODEL; PHENOTYPES; GLIOMAS; GROWTH; CANCER AB Diffusion of biological compounds, including nutrients, oxygen, and chemoattractants, is a common component of biomedical engineering models. Conventional numerical schemes, such as alternating direction implicit (ADI) for diffusion, are frequently the computational bottleneck. Our study employs graphics processing unit (GPU) technology to accelerate the diffusion model simulation. We tailor, implement, analyze, and test several parallel ADI algorithms on the highly parallel computational and data architecture of the GPU. Our study confirms that the proposed algorithms provide fast, high-quality simulation results suitable for inclusion in numerous bioengineering simulations. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Jiang, Beini; Struthers, Allan; Zhang, Le] Michigan Tech Univ, Dept Math Sci, Houghton, MI 49931 USA. [Sun, Zhe] Massachusetts Gen Hosp, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA USA. [Feng, Zhuo; Zhao, Xuqian] Michigan Tech Univ, Dept Elect & Comp Engn, Houghton, MI 49931 USA. [Zhao, Kaiyong] Hong Kong Baptist Univ, Dept Comp Sci, Hong Kong, Hong Kong, Peoples R China. [Dai, Weizhong] Louisiana Tech Univ, Coll Engn & Sci, Ruston, LA 71270 USA. [Zhou, Xiaobo] Methodist Hosp, Dept Pathol, Res Inst, Houston, TX 77030 USA. [Zhou, Xiaobo] Methodist Hosp, Res Inst, Ctr Bioinformat, Houston, TX 77030 USA. [Zhou, Xiaobo] Weill Cornell Med Coll, Houston, TX USA. [Berens, Michael E.] TGen, Translat Genom Res Inst, Canc & Cell Biol Div, Phoenix, AZ 85005 USA. RP Zhang, L (reprint author), Michigan Tech Univ, Dept Math Sci, Fisher Hall 216, Houghton, MI 49931 USA. EM mberens@tgen.org; zhangle@mtu.edu FU Mathematical Department Michigan Tech University; Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging; Department of Radiology at Massachusetts General Hospital and Translational Genomic Research Institute FX This work has been supported by startup funding of Mathematical Department Michigan Tech University, the Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital and Translational Genomic Research Institute. NR 58 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2040-7939 J9 INT J NUMER METH BIO JI Int. J. Numer. Meth. Biomed. PD NOV PY 2011 VL 27 IS 11 BP 1829 EP 1849 DI 10.1002/cnm.1444 PG 21 WC Engineering, Biomedical; Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Engineering; Mathematical & Computational Biology; Mathematics GA 853YG UT WOS:000297461000008 ER PT J AU Potsidis, E Berson, EL Sandberg, MA AF Potsidis, Emorfily Berson, Eliot L. Sandberg, Michael A. TI Disease Course of Patients with Unilateral Pigmentary Retinopathy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINITIS-PIGMENTOSA; MUTATIONS; RATES; GENE AB PURPOSE. To evaluate the change in ocular function by eye in patients with unilateral pigmentary retinopathy. METHODS. Longitudinal regression was used to estimate mean exponential rates of change in Goldmann visual field area (V4e white test light) and in full-field electroretinogram (ERG) amplitudes to 0.5- and 30-Hz white flashes in 15 patients with unilateral pigmentary retinopathy. Snellen visual acuity was assessed case by case. RESULTS. Mean annual rates of change for the affected eyes were -4.9% for visual field area, -4.7% for ERG amplitude to 0.5-Hz flashes, and -4.6% for ERG amplitude to 30-Hz flashes. All three rates were faster than the corresponding age-related rates of change for the fellow normal eyes (P = 0.0006, P = 0.003, P = 0.03, respectively). An initial cone ERG implicit time to 30-Hz flashes in affected eyes >= 40 ms predicted a faster mean rate of decline of visual field area and of ERG amplitude to 0.5- and 30-Hz flashes (P < 0.0001 for all three measures). The visual acuity of affected eyes was more likely to decrease in patients presenting at >35 years of age than in patients presenting at a younger age (P = 0.0004). CONCLUSIONS. The affected eye in unilateral pigmentary retinopathy shows a progressive loss of peripheral retinal function that cannot be attributed to aging alone and that is faster in eyes with a more prolonged initial cone ERG implicit time. Patients presenting at >35 years of age are at greater risk for losing visual acuity. (Invest Ophthalmol Vis Sci. 2011;52:9244-9249) DOI: 10.1167/iovs.11-7892 C1 [Potsidis, Emorfily; Berson, Eliot L.; Sandberg, Michael A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Berman Gund Lab, Study Retinal Degenerat,Med Sch, Boston, MA 02114 USA. RP Sandberg, MA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Berman Gund Lab, Study Retinal Degenerat,Med Sch, 243 Charles St, Boston, MA 02114 USA. EM michael_sandberg@meei.harvard.edu FU National Eye Institute [EY00169, EY019767]; The Foundation Fighting Blindness (Columbia, MD) FX Supported in part by National Eye Institute Grants EY00169 and EY019767 and The Foundation Fighting Blindness (Columbia, MD). NR 17 TC 2 Z9 2 U1 0 U2 3 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 NOV PY 2011 VL 52 IS 12 BP 9244 EP 9249 DI 10.1167/iovs.11-7892 PG 6 WC Ophthalmology SC Ophthalmology GA 856IB UT WOS:000297631400060 PM 21989720 ER PT J AU Sels, JWEM Tonino, PAL Siebert, U Fearon, WF Van't Veer, M De Bruyne, B Pijls, NHJ AF Sels, Jan-Willem E. M. Tonino, Pim A. L. Siebert, Uwe Fearon, William F. Van't Veer, Marcel De Bruyne, Bernard Pijls, Nico H. J. TI Fractional Flow Reserve in Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction Experience From the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) Study SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE FAME study; FFR; multivessel disease; NSTEMI; PCI; unstable angina ID PERCUTANEOUS CORONARY INTERVENTION; ARTERY-DISEASE; LESIONS; ANGIOPLASTY; REVASCULARIZATION; SEVERITY; PECTORIS AB Objectives The aim of this study was to study whether there is a difference in benefit of fractional flow reserve (FFR) guidance for percutaneous coronary intervention (PCI) in multivessel coronary disease in patients with unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI), compared with stable angina (SA). Background The use of FFR to guide PCI has been well established for patients with SA. Its use in patients with UA or NSTEMI has not been investigated prospectively. Methods In the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) study 1,005 patients with multivessel disease amenable to PCI were included and randomized to either angiography-guided PCI of all lesions >= 50% or FFR-guided PCI of lesions with an FFR >= 0.80. Patients admitted for UA or NSTEMI with positive troponin but total creatine kinase < 1,000 U/I were eligible for inclusion. We determined 2-year major adverse cardiac event rates of these patients and compared it with stable patients. Results Of 1,005 patients, 328 had UA or NSTEMI. There was no evidence for heterogeneity among the subgroups for any of the outcome variables (all p values > 0.05). Using FFR to guide PCI resulted in similar risk reductions of major adverse cardiac events and its components in patients with UA or NSTEMI, compared with patients with SA (absolute risk reduction of 5.1% vs. 3.7%, respectively, p = 0.92). In patients with UA or NSTEMI, the number of stents was reduced without increase in hospital stay or procedure time and with less contrast use, in similarity to stable patients. Conclusions The benefit of using FFR to guide PCI in multivessel disease does not differ between patients with UA or NSTEMI, compared with patients with SA. (J Am Coll Cardiol Intv 2011;4: 1133-9) (C) 2011 by the American College of Cardiology Foundation C1 [Pijls, Nico H. J.] Univ Technol, Catharina Hosp, Dept Cardiol, NL-5602 ZA Eindhoven, Netherlands. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Fearon, William F.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [De Bruyne, Bernard] Cardiovasc Ctr Aalst, Aalst, Belgium. RP Pijls, NHJ (reprint author), Univ Technol, Catharina Hosp, Dept Cardiol, Michelangelolaan 2,POB 1350, NL-5602 ZA Eindhoven, Netherlands. EM carias@cze.nl FU Radi Medical Systems, Uppsala, Sweden; Stichting Vrienden van het Hart Zuidoost Brabant, the Netherlands; St. Jude Medical FX The FAME study was supported by unrestricted research grants from Radi Medical Systems, Uppsala, Sweden and Stichting Vrienden van het Hart Zuidoost Brabant, the Netherlands. Dr. Tonino has received lecture fees from St. Jude Medical. Drs. Fearon and De Bruyne report institutional research grants from St. Jude Medical. Dr. Pip received an educational grant for the Catharina Hospital from St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 24 TC 54 Z9 57 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD NOV PY 2011 VL 4 IS 11 BP 1183 EP 1189 DI 10.1016/j.jcin.2011.08.008 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 856RW UT WOS:000297662100004 PM 22115657 ER PT J AU Don, CW House, J White, C Kiernan, T Weideman, M Ruggiero, N McCann, A Rosenfield, K AF Don, Creighton W. House, John White, Christopher Kiernan, Thomas Weideman, Mary Ruggiero, Nicholas McCann, Andrew Rosenfield, Kenneth TI Carotid Revascularization immediately Before Urgent Cardiac Surgery Practice Patterns Associated With the Choice of Carotid Artery Stenting or Endarterectomy: A Report From the CARE (Carotid Artery Revascularization and Endarterectomy) Registry SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE carotid artery stenting; carotid endarterectomy; carotid revascularization ID SINGLE-CENTER EXPERIENCE; CORONARY-BYPASS; HIGH-RISK; STENOSIS; OUTCOMES; ANGIOPLASTY; DISEASE AB Objectives We describe characteristics associated with use of endarterectomy (CEA) versus stenting (CAS) in patients before urgent cardiac surgery. Background The optimal modality of carotid revascularization preceding cardiac surgery is unknown. Methods Retrospective evaluation of the CARE (Carotid Artery Revascularization and Endarterectomy) registry from January 2005 to April 2010 was performed on patients undergoing CEA or CAS preceding urgent cardiac surgery within 30 days. Baseline characteristics were compared, and multivariate adjustment was performed. Results Of 451 patients who met study criteria, 255 underwent CAS and 196 underwent CEA. Both procedures increased over time to a similar degree (p = 0.18). Patients undergoing CAS had more frequent history of peripheral artery disease (38.2% vs. 26.5%, p < 0.01), neck surgery (5.5% vs. 1.0%, p = 0.01), neck radiation (4.3% vs. 1.0%, p = 0.04), left-main coronary disease (34.8% vs. 23.5%, p < 0.01), neurological events (45.8% vs. 31.3%, p < 0.01), carotid intervention (20.8% vs. 7.6%, p < 0.01), and higher baseline creatinine (1.3 vs. 1.1 mg/dl, p = 0.02). The target carotid arteries of CAS patients were more likely to be symptomatic in the 6 months before revascularization and have restenosis from prior CEA. Patients undergoing CAS had a lower American Society of Anesthesiology grade. Midwest hospitals were less likely to perform CAS than CEA, whereas in the other regions CAS was more common (p < 0.01). Non-Caucasian race, a history of heart failure, previous carotid procedures, prior stroke, left main coronary artery stenosis, lower American Society of Anesthesiology grade, and teaching hospital were independent predictors of patients who would receive CAS. Conclusions Carotid artery stenting and CEA have increased among patients undergoing urgent cardiac surgery. Patients who underwent CAS had more vascular disease but lower acute pre-surgical risk. Significant regional variation in procedure selection exists. (J Am Coll Cardiol Intv 2011;4: 1200-8) (C) 2011 by the American College of Cardiology Foundation C1 [Don, Creighton W.] Univ Washington, Med Ctr, Div Cardiol, Seattle, WA 98195 USA. [House, John] St Lukes Mid Amer Heart & Vasc Inst, Kansas City, MO USA. [White, Christopher] Ochsner Heart & Vasc Clin, New Orleans, LA USA. [Weideman, Mary] Amer Coll Cardiol, Washington, DC USA. [Kiernan, Thomas] Natl Univ Ireland Univ Coll Cork, Sch Med, Cork Univ Hosp, Cork, Ireland. [Ruggiero, Nicholas] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [McCann, Andrew] Princess Alexandra Hosp, Brisbane, Qld 4102, Australia. [Rosenfield, Kenneth] Massachusetts Gen Hosp, Cardiac & Vasc Invas Serv, Boston, MA 02114 USA. RP Don, CW (reprint author), Univ Washington, Med Ctr, Med Div Cardiol, 1959 NE Pacific St, Seattle, WA 98195 USA. EM cwdon@u.washington.edu RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 FU NCRR [5 KL2 RR025015]; Abbott Vascular; Lutonix; Atrium; IDEV FX This study was funded under NCRR Grant 5 KL2 RR025015. Dr. Rosenfield is a consultant for Abbott Vascular; has received royalty for Angioguard from Cordis; and has received research support from Abbott Vascular, Lutonix, Atrium, and IDEV. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. George W. Vetrovec, MD, has served as Guest Editor for this paper. NR 21 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD NOV PY 2011 VL 4 IS 11 BP 1200 EP 1208 DI 10.1016/j.jcin.2011.09.010 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 856RW UT WOS:000297662100007 PM 22115660 ER PT J AU Wood, MJ AF Wood, Malissa J. TI NADPH oxidase: short-term foe, long-term friend SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Editorial Material ID MYOCARDIAL INJURY; BOSTON-MARATHON; OXYGEN RADICALS; EXERCISE; CARDIOPROTECTION; INCREASES C1 Massachusetts Gen Hosp, MGH Heart Ctr, Corrigan Womens Heart Hlth Program, Boston, MA 02114 USA. RP Wood, MJ (reprint author), Massachusetts Gen Hosp, MGH Heart Ctr, Corrigan Womens Heart Hlth Program, 55 Fruit St Blake 256, Boston, MA 02114 USA. EM mjwood@partners.org NR 9 TC 0 Z9 0 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 2011 VL 111 IS 5 BP 1231 EP 1232 DI 10.1152/japplphysiol.01060.2011 PG 2 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 856ZX UT WOS:000297684500002 PM 21885801 ER PT J AU de Prost, N Costa, EL Wellman, T Musch, G Winkler, T Tucci, MR Harris, RS Venegas, JG Melo, MFV AF de Prost, Nicolas Costa, Eduardo L. Wellman, Tyler Musch, Guido Winkler, Tilo Tucci, Mauro R. Harris, R. Scott Venegas, Jose G. Melo, Marcos F. Vidal TI Effects of surfactant depletion on regional pulmonary metabolic activity during mechanical ventilation SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE fluorodeoxyglucose F18; positron emission tomography; pulmonary edema; pulmonary surfactant; respiratory distress syndrome; adult; ventilator-induced lung injury ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; POSITRON-EMISSION-TOMOGRAPHY; END-EXPIRATORY PRESSURE; REPETITIVE COLLAPSE; EXPERIMENTAL-MODEL; F-18-FDG UPTAKE; TIDAL VOLUMES; ANIMAL-MODELS; SHEEP LUNGS AB de Prost N, Costa EL, Wellman T, Musch G, Winkler T, Tucci MR, Harris RS, Venegas JG, Vidal Melo MF. Effects of surfactant depletion on regional pulmonary metabolic activity during mechanical ventilation. J Appl Physiol 111: 1249-1258, 2011. First published July 28, 2011; doi:10.1152/japplphysiol.00311.2011.-Inflammation during mechanical ventilation is thought to depend on regional mechanical stress. This can be produced by concentration of stresses and cyclic recruitment in low-aeration dependent lung. Positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) allows for noninvasive assessment of regional metabolic activity, an index of neutrophilic inflammation. We tested the hypothesis that, during mechanical ventilation, surfactant-depleted low-aeration lung regions present increased regional (18)F-FDG uptake suggestive of in vivo increased regional metabolic activity and inflammation. Sheep underwent unilateral saline lung lavage and were ventilated supine for 4 h (positive end-expiratory pressure = 10 cmH(2)O, tidal volume adjusted to plateau pressure = 30 cmH(2)O). We used PET scans of injected (13)N-nitrogen to compute regional perfusion and ventilation and injected (18)F-FDG to calculate (18)F-FDG uptake rate. Regional aeration was quantified with transmission scans. Whole lung (18)F-FDG uptake was approximately two times higher in lavaged than in nonlavaged lungs (2.9 +/- 0.6 vs. 1.5 +/- 0.3 10(-3)/min; P < 0.05). The increased (18)F-FDG uptake was topographically heterogeneous and highest in dependent low-aeration regions (gas fraction 10-50%, P < 0.001), even after correction for lung density and wet-to-dry lung ratios. (18)F-FDG uptake in low-aeration regions of lavaged lungs was higher than that in low-aeration regions of nonlavaged lungs (P < 0.05). This occurred despite lower perfusion and ventilation to dependent regions in lavaged than nonlavaged lungs (P < 0.001). In contrast, (18)F-FDG uptake in normally aerated regions was low and similar between lungs. Surfactant depletion produces increased and heterogeneously distributed pulmonary (18)F-FDG uptake after 4 h of supine mechanical ventilation. Metabolic activity is highest in poorly aerated dependent regions, suggesting local increased inflammation. C1 [de Prost, Nicolas; Costa, Eduardo L.; Wellman, Tyler; Musch, Guido; Winkler, Tilo; Tucci, Mauro R.; Venegas, Jose G.; Melo, Marcos F. Vidal] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Harris, R. Scott] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Harris, R. Scott] Harvard Univ, Sch Med, Boston, MA USA. [Costa, Eduardo L.; Tucci, Mauro R.] Univ Sao Paulo, Sch Med, Resp Intens Care Unit, Sao Paulo, Brazil. [Wellman, Tyler] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM mvidalmelo@partners.org RI Winkler, Tilo/B-5337-2009; OI Winkler, Tilo/0000-0002-7276-5550; de Prost, Nicolas/0000-0002-4833-4320 FU National Heart, Lung, and Blood Institute [HL-5R01HL086827]; Fondation Recherche Medicale (FRM); College des Enseignants de Pneumologie (CEP); AstraZeneca; CAPES (Brazilian Ministry of Education); [5K08HL076464] FX This study was supported by National Heart, Lung, and Blood Institute Grant HL-5R01HL086827. G. Musch received salary support from 5K08HL076464, N. de Prost received a scholarship from the Fondation Recherche Medicale (FRM) and from the College des Enseignants de Pneumologie (CEP) with the support of AstraZeneca, and M. R. Tucci received a scholarship from CAPES (Brazilian Ministry of Education). NR 69 TC 23 Z9 23 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 2011 VL 111 IS 5 BP 1249 EP 1258 DI 10.1152/japplphysiol.00311.2011 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 856ZX UT WOS:000297684500006 PM 21799132 ER PT J AU Beinart, R Abbara, S Blum, A Ferencik, M Heist, K Ruskin, J Mansour, M AF Beinart, Roy Abbara, Suhny Blum, Andrew Ferencik, Maros Heist, Kevin Ruskin, Jeremy Mansour, Moussa TI Left Atrial Wall Thickness Variability Measured by CT Scans ?in Patients Undergoing Pulmonary Vein Isolation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; catheter ablation; CT scan; left atrium; pulmonary vein isolation ID RADIOFREQUENCY CATHETER ABLATION; FIBRILLATION ABLATION; FISTULA; ANATOMY; HEART; PREVENTION; ESOPHAGUS; VOLUME; MODEL; TRIAL AB Left Atrial Wall Thickness Variability Measured by CT Scans. Introduction: Successful catheter ablation of atrial fibrillation (AF) requires the creation of transmural lesions in the left atrium (LA). In addition, cardiac perforation is more likely to occur in areas of thin walls. The LA wall thickness is thus relevant both for procedural efficacy and safety. This study sought to evaluate the regional LA wall thickness in patients with AF. Methods: The LA muscular wall thickness (excluding fat) was measured by 64 slice cardiac computed tomography (CT) in 60 patients with persistent AF prior to catheter ablation procedures. Measurements were performed in all patients at 12 distinct LA locations, including 3 at the roof (right, middle left), 3 at the floor (right, middle, left), 4 at the posterior wall (right, middle, middle-superior, left), 1 at the left lateral ridge (LLR), and 1 at the mitral isthmus. Results: There was a large range of LA wall thickness (average thickness 1.89 +/- 0.48 mm, range 0.53.5 mm). In addition, there were significant regional differences in LA wall thickness. In particular, the LA roof was significantly thicker than the posterior wall and floor (P < 0.001), the LLR was significantly thicker than most regions (P < 0.04), and themitral isthmus was also significantly thicker than the posterior wall (P < 0.001) and floor (P < 0.001). Conclusions: In patients with persistent AF, there is inter-and intra-patient variability in the thickness of the LA muscular wall. In most patients, however, the roof, mitral isthmus, and the ridge between the pulmonary veins and appendage are thicker compared to the posterior wall and floor. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1232-1236, November 2011) C1 [Beinart, Roy; Abbara, Suhny; Blum, Andrew; Ferencik, Maros; Heist, Kevin; Ruskin, Jeremy; Mansour, Moussa] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Ctr Heart, Boston, MA 02114 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Ctr Heart, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org FU Deane Institute for Integrative Research in Stroke and Atrial Fibrillation FX This work has been partially supported by the Deane Institute for Integrative Research in Stroke and Atrial Fibrillation. NR 37 TC 24 Z9 24 U1 0 U2 2 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 NOV PY 2011 VL 22 IS 11 BP 1232 EP 1236 DI 10.1111/j.1540-8167.2011.02100.x PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 858XQ UT WOS:000297837000008 PM 21615817 ER PT J AU Sharma, AK Chander, R Singh, JP AF Sharma, Ajay K. Chander, Ravi Singh, Jagmeet P. TI AV Nodal Ablation-Induced Gerbode Defect (LV-RA Shunt) SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE AV nodal ablation; Gerbode defect; LV-RA shunt ID RIGHT ATRIAL SHUNT AB Ventriculoatrial Shunt After Nodal Ablation. A Gerbode defect that comprises a left ventricular to right atrial shunt is usually a congenital cardiac condition. Rarely, acquired Gerbode defects secondary to aortic or tricuspid valve endocarditis have been reported. We present a case of a Gerbode defect caused by catheter ablation of the AV node in a patient with a severely dilated cardiomyopathy and refractory atrial fibrillation. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1288-1289, November 2011) C1 [Singh, Jagmeet P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Sharma, Ajay K.] Charlton Mem Hosp, Dept Internal Med, Fall River, MA USA. [Chander, Ravi] Charlton Mem Hosp, Dept Cardiol, Fall River, MA USA. [Singh, Jagmeet P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org FU Boston Scientific, Biotronik, Medtronic, St. Jude Medical FX Dr. Singh reports participation on research grants supported by Boston Scientific, Biotronik, Medtronic, St. Jude Medical, and Sorin Group. Other authors: no disclosures. NR 6 TC 7 Z9 7 U1 1 U2 2 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 NOV PY 2011 VL 22 IS 11 BP 1288 EP 1289 DI 10.1111/j.1540-8167.2011.02111.x PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 858XQ UT WOS:000297837000019 PM 21649778 ER PT J AU Peacock, ZS Resnick, CM Faquin, WC Kaban, LB AF Peacock, Zachary S. Resnick, Cory M. Faquin, William C. Kaban, Leonard B. TI Accessory Mandibular Condyle at the Coronoid Process SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Mandibular condyle; Jacob disease; accessory condyle; coronoid hyperplasia; mandibular hypomobility ID PROCESS JACOBS-DISEASE; CRANIAL NEURAL CREST; OF-THE-LITERATURE; BIFID CONDYLE; DUPLICATION; OSTEOCHONDROMA; HYPERPLASIA; NEUROCRISTOPATHY; MAXILLARY; GROWTH AB Coronoid process hyperplasia is a rare cause of mandibular hypomobility. It can result from temporalis muscle hyperactivity, trauma, and neoplasia, but often is idiopathic. Enlargement of the coronoid process leading to pseudojoint formation with the zygomatic arch is known as Jacob's disease. It results most commonly from an osteochondroma of the coronoid process. This is the first reported case of a non-neoplastic accessory mandibular condyle located at the coronoid process articulating with the zygoma. C1 [Peacock, Zachary S.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Peacock, ZS (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM zpeacock@partners.org OI Resnick, Cory/0000-0002-6391-9618 NR 38 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD NOV PY 2011 VL 22 IS 6 BP 2168 EP 2171 DI 10.1097/SCS.0b013e3182323fed PG 4 WC Surgery SC Surgery GA 857TE UT WOS:000297741900065 PM 22075815 ER PT J AU Beinart, R Kabra, R Heist, KE Blendea, D Barrett, CD Danik, SB Collins, R Ruskin, JN Mansour, M AF Beinart, Roy Kabra, Rajesh Heist, Kevin E. Blendea, Dan Barrett, Conor D. Danik, Stephan B. Collins, Ryan Ruskin, Jeremy N. Mansour, Moussa TI Respiratory compensation improves the accuracy of electroanatomic mapping of the left atrium and pulmonary veins during atrial fibrillation ablation SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Article DE Atrial fibrillation; Catheter ablation; Cardiac mapping ID CATHETER ABLATION; COMPUTED-TOMOGRAPHY; IMAGE INTEGRATION; VENOUS ANATOMY; HEART RHYTHM; IMPACT AB Background The creation of accurate electroanatomic maps (EAM) of the left atrium and pulmonary veins is important for atrial fibrillation (AF) ablation to guide ablative lesions and improve the safety and efficacy of the procedure. Respiratory motion of the heart and the pulmonary veins affects the accuracy of these maps. Purpose This study aims to assess changes in the left atrial and pulmonary venous anatomy due to respiration and to evaluate their implication for EAM acquisition. Methods Two separate EAM were created using the CARTO 3 mapping system in 22 consecutive patients (63% males; mean age, 63 +/- 8 years) undergoing AF ablation at our center: a non-respiratory compensation (RC) map in which endocardial points were collected irrespective of respiratory phase and an RC map in which the points were collected during end expiration only. These maps were compared to pre-procedural cardiac CT/MRI images. Results Non-RC mapping required 3.2 +/- 1.0 min versus 7.8 +/- 2.1 min for the maps with RC. In comparison to the pre-procedural CT/MRI images, maps without RC significantly overestimated the dimensions of the pulmonary veins' ostia compared to maps with RC in both long and short axes. Distances between the pulmonary veins were not significantly different when comparing non-RC to RC mapping at the left atrial roof or floor. Conclusions Respiratory compensation at the time of EAM acquisition during AF ablation more accurately represents the true anatomical dimensions of the pulmonary vein ostia. The resulting more accurate maps may improve the safety and efficacy of atrial fibrillation ablation. C1 [Mansour, Moussa] Massachusetts Gen Hosp, Cardiac Arrhythmia Unit, Boston, MA 02114 USA. [Beinart, Roy; Kabra, Rajesh; Heist, Kevin E.; Blendea, Dan; Barrett, Conor D.; Danik, Stephan B.; Ruskin, Jeremy N.; Mansour, Moussa] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. [Collins, Ryan] Biosense Webster Incorp, Diamond Bar, CA USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Unit, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org FU MGH Deane Institute for Integrative Research in Stroke and Atrial Fibrillation FX This work was supported in part by the MGH Deane Institute for Integrative Research in Stroke and Atrial Fibrillation. NR 15 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1383-875X J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PD NOV PY 2011 VL 32 IS 2 BP 105 EP 110 DI 10.1007/s10840-011-9583-z PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 855II UT WOS:000297556800005 PM 21607726 ER PT J AU Buckner, RL Krienen, FM Castellanos, A Diaz, JC Yeo, BTT AF Buckner, Randy L. Krienen, Fenna M. Castellanos, Angela Diaz, Julio C. Yeo, B. T. Thomas TI The organization of the human cerebellum estimated by intrinsic functional connectivity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE somatotopy; motor control; prefrontal; functional magnetic resonance imaging; default network; connectome ID HUMAN CEREBRAL-CORTEX; BRAINS DEFAULT NETWORK; SURFACE-BASED ANALYSIS; DEMENTED OLDER-ADULTS; OPEN ACCESS SERIES; RHESUS-MONKEY; CORTICAL SURFACE; MOTOR CORTEX; CORTICOPONTINE PROJECTION; GEOMETRICALLY ACCURATE AB Buckner RL, Krienen FM, Castellanos A, Diaz JC, Yeo BT. The organization of the human cerebellum estimated by intrinsic functional connectivity. J Neurophysiol 106: 2322-2345, 2011. First published July 27, 2011; doi:10.1152/jn.00339.2011.-The cerebral cortex communicates with the cerebellum via polysynaptic circuits. Separate regions of the cerebellum are connected to distinct cerebral areas, forming a complex topography. In this study we explored the organization of cerebrocerebellar circuits in the human using resting-state functional connectivity MRI (fcMRI). Data from 1,000 subjects were registered using nonlinear deformation of the cerebellum in combination with surface-based alignment of the cerebral cortex. The foot, hand, and tongue representations were localized in subjects performing movements. fcMRI maps derived from seed regions placed in different parts of the motor body representation yielded the expected inverted map of somatomotor topography in the anterior lobe and the upright map in the posterior lobe. Next, we mapped the complete topography of the cerebellum by estimating the principal cerebral target for each point in the cerebellum in a discovery sample of 500 subjects and replicated the topography in 500 independent subjects. The majority of the human cerebellum maps to association areas. Quantitative analysis of 17 distinct cerebral networks revealed that the extent of the cerebellum dedicated to each network is proportional to the network's extent in the cerebrum with a few exceptions, including primary visual cortex, which is not represented in the cerebellum. Like somatomotor representations, cerebellar regions linked to association cortex have separate anterior and posterior representations that are oriented as mirror images of one another. The orderly topography of the representations suggests that the cerebellum possesses at least two large, homotopic maps of the full cerebrum and possibly a smaller third map. C1 [Buckner, Randy L.; Krienen, Fenna M.; Castellanos, Angela; Yeo, B. T. Thomas] Harvard Univ, Ctr Brain Sci, Dept Psychol, Cambridge, MA 02138 USA. [Buckner, Randy L.; Castellanos, Angela; Diaz, Julio C.] Howard Hughes Med Inst, Cambridge, England. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Buckner, Randy L.; Krienen, Fenna M.; Yeo, B. T. Thomas] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Diaz, Julio C.] Univ Miami, Dept Biol, Miami, FL USA. RP Buckner, RL (reprint author), Harvard Univ, Ctr Brain Sci, Dept Psychol, 52 Oxford St,Northwest Bldg 280-06, Cambridge, MA 02138 USA. EM randy_buckner@harvard.edu OI Yeo, B.T. Thomas/0000-0002-0119-3276 FU Department of Defense; Ashford Graduate Fellowship in the Sciences; Sackler Scholars Program in Psychobiology; Howard Hughes Medical Institute; National Institutes of Health [AG021910, P41 RR14074, K08 MH067966]; Massachusetts General Hospital-University of California [U54MH091665]; Simons Foundation FX We thank Jeremy Schmahmann for discussion, the Harvard Center for Brain Science Neuroimaging Core and the Athinoula A. Martinos Center for imaging support, the Harvard FAS Research Computing Group (in particular James Cuff, Jerry Lotto, and Jeff Chang), and the Neuroinformatics Research Group (Gabriele Fariello, Timothy O'Keefe, and Victor Petrov). We thank Haderer & Muller Biomedical Art for assistance with Fig. 5. F. M. Krienen was supported by fellowships from the Department of Defense, an Ashford Graduate Fellowship in the Sciences, and the Sackler Scholars Program in Psychobiology. A. Castellanos and J. C. Diaz were supported by the Howard Hughes Medical Institute Exceptional Research Opportunities Program.; This work was supported by National Institutes of Health Grants AG021910, P41 RR14074, and K08 MH067966, the Massachusetts General Hospital-University of California, Los Angeles Human Connectome Project (U54MH091665), the Howard Hughes Medical Institute, and the Simons Foundation. NR 111 TC 326 Z9 327 U1 6 U2 58 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2011 VL 106 IS 5 BP 2322 EP 2345 DI 10.1152/jn.00339.2011 PG 24 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 857CA UT WOS:000297690500019 PM 21795627 ER PT J AU Cokol, M Chua, HN Tasan, M Mutlu, B Weinstein, ZB Suzuki, Y Nergiz, ME Costanzo, M Baryshnikova, A Giaever, G Nislow, C Myers, CL Andrews, BJ Boone, C Roth, FP AF Cokol, Murat Chua, Hon Nian Tasan, Murat Mutlu, Beste Weinstein, Zohar B. Suzuki, Yo Nergiz, Mehmet E. Costanzo, Michael Baryshnikova, Anastasia Giaever, Guri Nislow, Corey Myers, Chad L. Andrews, Brenda J. Boone, Charles Roth, Frederick P. TI Systematic exploration of synergistic drug pairs SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE chemical genetics; drug combinations; drug discovery; genetic interactions ID GENETIC INTERACTION; COMBINATIONS; YEAST; NETWORK; THERAPEUTICS; ANTIBIOTICS; INFECTIONS; DISCOVERY; RELEVANT AB Drug synergy allows a therapeutic effect to be achieved with lower doses of component drugs. Drug synergy can result when drugs target the products of genes that act in parallel pathways ('specific synergy'). Such cases of drug synergy should tend to correspond to synergistic genetic interaction between the corresponding target genes. Alternatively, 'promiscuous synergy' can arise when one drug non-specifically increases the effects of many other drugs, for example, by increased bioavailability. To assess the relative abundance of these drug synergy types, we examined 200 pairs of antifungal drugs in S. cerevisiae. We found 38 antifungal synergies, 37 of which were novel. While 14 cases of drug synergy corresponded to genetic interaction, 92% of the synergies we discovered involved only six frequently synergistic drugs. Although promiscuity of four drugs can be explained under the bioavailability model, the promiscuity of Tacrolimus and Pentamidine was completely unexpected. While many drug synergies correspond to genetic interactions, the majority of drug synergies appear to result from non-specific promiscuous synergy. Molecular Systems Biology 7: 544; published online 8 November 2011; doi:10.1038/msb.2011.71 C1 [Cokol, Murat; Mutlu, Beste; Weinstein, Zohar B.] Sabanci Univ, Biol Sci & Bioengn Program, Fac Engn & Nat Sci, TR-34956 Istanbul, Turkey. [Cokol, Murat; Chua, Hon Nian; Tasan, Murat; Suzuki, Yo; Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Chua, Hon Nian; Tasan, Murat; Costanzo, Michael; Baryshnikova, Anastasia; Giaever, Guri; Nislow, Corey; Andrews, Brenda J.; Boone, Charles; Roth, Frederick P.] Univ Toronto, Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada. [Suzuki, Yo] J Craig Venter Inst, Dept Synthet Biol & Bioenergy, San Diego, CA USA. [Nergiz, Mehmet E.] Zirve Univ, Dept Comp Engn, Fac Engn, Gaziantep, Turkey. [Giaever, Guri; Nislow, Corey; Andrews, Brenda J.; Boone, Charles; Roth, Frederick P.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada. [Giaever, Guri] Univ Toronto, Dept Pharmaceut Sci, Toronto, ON M5S 3E1, Canada. [Myers, Chad L.] Univ Minnesota Twin Cities, Dept Comp Sci & Engn, Minneapolis, MN USA. [Roth, Frederick P.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Roth, Frederick P.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Cokol, M (reprint author), Sabanci Univ, Biol Sci & Bioengn Program, Fac Engn & Nat Sci, TR-34956 Istanbul, Turkey. EM cokol@sabanciuniv.edu; fritz.roth@utoronto.edu RI Giaever, Guri/D-3930-2009; Roth, Frederick/H-6308-2011; OI Baryshnikova, Anastasia/0000-0002-0123-2052; Roth, Frederick/0000-0002-6628-649X FU NIH [GM086115, HG004098, HG005853-01, HG003224, HG004756, CA130266, MH087394, HG004233]; FP7 Marie Curie IRG Grant [268440]; Scientific and Technological Research Council of Turkey [110S209]; Agency of Science, Technology and Research, Singapore; Canadian Institutes of Health [MOP-81340, MOP-84305]; Canadian Institute for Advanced Research; Canada Excellence Research Chair FX We are indebted to the anonymous reviewers, whose initial comments substantially changed the direction of this study. We thank F Ozbay, C Cenik, I Iossifov, M Yildirim, E Demir, J Mellor, R Deo, and Y Bulut for their valuable comments, and to S Buratowski, N Gray, and C Shamu for providing reagents. M Cokol (MC1) and MT were supported by NIH Fellowships (GM086115 and HG004098, respectively). MC1 was supported by a FP7 Marie Curie IRG Grant (268440) and Scientific and Technological Research Council of Turkey (110S209). HNC was supported by the Agency of Science, Technology and Research, Singapore. CN and GG were supported by the Canadian Institutes of Health (MOP-81340 and MOP-84305). M Costanzo (MC2), AB, CLM, BJA, and CB were supported by a grant from the National Institutes of Health (HG005853-01). FPR was supported by NIH grants (HG003224, HG004756, CA130266, MH087394 and HG004233), a Canadian Institute for Advanced Research Fellowship and a Canada Excellence Research Chair. NR 32 TC 80 Z9 80 U1 1 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD NOV PY 2011 VL 7 AR 544 DI 10.1038/msb.2011.71 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 857AK UT WOS:000297685900001 PM 22068327 ER PT J AU Hirschberg, R Giacino, JT AF Hirschberg, Ron Giacino, Joseph T. TI The Vegetative and Minimally Conscious States: Diagnosis, Prognosis and Treatment SO NEUROLOGIC CLINICS LA English DT Article DE Consciousness; Vegetative state; Traumatic brain injury; Neuroimaging; Outcomes ID TRAUMATIC BRAIN-INJURY; FOLLOW-UP; DISORDERS; ZOLPIDEM; RECOVERY; SCALE; COMA; RECOMMENDATIONS; REHABILITATION; AMANTADINE AB Severe acquired brain injury has profound impact on alertness, cognition, and behavior. Among those who survive the initial injury, a significant minority fail to fully recover self and environmental awareness, and go on to experience prolonged disorders of consciousness (DOC) that can last a lifetime. Although there are no standards of care to guide clinical management, a growing body of empirical evidence is beginning to accrue to inform clinical decision making. In this article, we review the state of the science as it pertains to diagnosis, prognosis, and treatment of patients with DOC. C1 [Hirschberg, Ron; Giacino, Joseph T.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Hirschberg, Ron; Giacino, Joseph T.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02115 USA. [Hirschberg, Ron] Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Giacino, Joseph T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Giacino, JT (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. EM jgiacino@partners.org NR 51 TC 32 Z9 40 U1 0 U2 22 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD NOV PY 2011 VL 29 IS 4 BP 773 EP + DI 10.1016/j.ncl.2011.07.009 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 853BN UT WOS:000297401300006 PM 22032660 ER PT J AU Wilson, MR Roos, KL AF Wilson, Michael R. Roos, Karen L. TI Infectious Diseases and Impaired Consciousness SO NEUROLOGIC CLINICS LA English DT Article DE Neuroinfectious diseases; Infectious disease; Disorders of consciousness; Impaired consciousness ID RECONSTITUTION INFLAMMATORY SYNDROME; NERVOUS-SYSTEM INFECTIONS; STATUS EPILEPTICUS; PNEUMOCOCCAL MENINGITIS; CEREBROSPINAL-FLUID; UNITED-STATES; SEVERE SEPSIS; ENCEPHALITIS; EPIDEMIOLOGY; INFLUENZA AB Any of a number of neuroinfectious diseases can cause a disorder of consciousness. The priority in the care of the patient is to identify an infectious disease that is treatable. This article examines disorders of consciousness that may be caused by a septic encephalopathy, bacterial meningoencephalitis, viral encephalitis, tick-borne bacterial disease, fungal meningitis, tuberculous meningitis, a focal infectious mass lesion, such as a brain abscess, or an autoimmune-mediated disorder as a complication of infection. C1 [Roos, Karen L.] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. [Wilson, Michael R.] Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Roos, KL (reprint author), Indiana Univ Sch Med, Dept Neurol, Suite 1711,550 N Univ Blvd, Indianapolis, IN 46202 USA. EM kroos@iupui.edu RI Wilson, Michael/E-8095-2013 NR 42 TC 1 Z9 1 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 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD NOV PY 2011 VL 29 IS 4 BP 927 EP + DI 10.1016/j.ncl.2011.07.013 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 853BN UT WOS:000297401300013 PM 22032667 ER PT J AU Rubin, EB Bernat, JL AF Rubin, Emily B. Bernat, James L. TI Ethical Aspects of Disordered States of Consciousness SO NEUROLOGIC CLINICS LA English DT Article DE Disordered consciousness; Coma; Minimally conscious state; Vegetative state; Traumatic brain injury; Ethics; Surrogate decision making; End-of-life care ID PERSISTENT VEGETATIVE STATE; LIFE-SUSTAINING TREATMENT; ARTIFICIAL NUTRITION; MEDICAL FUTILITY; DECISION-MAKING; CRITICAL-CARE; BRAIN-INJURY; SUPPORT; PATIENT; LAWS AB The medical care of patients in disordered states of consciousness, including vegetative and minimally conscious states, raises some of the most intricate ethical questions in medicine. There is inherent ambiguity and uncertainty involved in diagnosing such patients and evaluating their level of awareness and prognosis for recovery. The care of these patients requires the weighing of competing ethical values, including respect for personal autonomy, protection of vulnerable patients, nonmaleficence, and the just use of limited medical resources. We highlight some of the major ethical issues in caring for patients with severe brain injury. C1 [Rubin, Emily B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bernat, James L.] Dartmouth Med Sch, Hanover, NH 03755 USA. [Bernat, James L.] Dartmouth Hitchcock Med Ctr, Dept Neurol, Lebanon, NH 03756 USA. RP Rubin, EB (reprint author), 29 Lawrence St,Apartment B, Cambridge, MA 02139 USA. EM erubin3@partners.org NR 48 TC 3 Z9 3 U1 1 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 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD NOV PY 2011 VL 29 IS 4 BP 1055 EP + DI 10.1016/j.ncl.2011.07.007 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 853BN UT WOS:000297401300019 PM 22032673 ER PT J AU Gladd, DK Saunders, GH AF Gladd, Dana K. Saunders, Gabrielle H. TI Ambient noise levels in the chemotherapy clinic SO NOISE & HEALTH LA English DT Article DE Chemotherapy; cisplatin; noise disturbance; noise ID OFFICE NOISE; STRESS; OTOTOXICITY; CISPLATIN; EXPOSURE AB Many of the drugs used for chemotherapy treatments are known to be ototoxic, and can result in permanent hearing threshold shifts. The degree of ototoxic damage can be influenced by many factors including dosage, duration of exposure, genetics, and coadministration with other ototoxic agents. Cisplatin is known for its ototoxic effects on hearing thresholds, particularly in the high frequencies. Recent studies have indicated a synergistic relationship between Cisplatin administration and moderate to high noise level exposure starting between 70-85 dB SPL. This study measured the noise levels in the Portland Veterans Affairs Medical Centers outpatient chemotherapy clinic. Average (LAeq) and peak (LCpeak) noise measures were recorded every minute from 7 am until 6 pm on the two busiest clinic days. Patients, visitors, and staff members filled out anonymous surveys regarding their reactions to noise levels. Cumulative noise levels were not at levels known to interact with Cisplatin for a significant period of time. Noise measurement analysis indicated that levels were at or above 70 dB SPL for less than ten minutes during the 11-hour recording window. The patient and visitor surveys indicated that both groups were unbothered by noise in the clinic. However, most staff members were bothered by or concerned about noise levels, and many felt that it caused stress and difficulty communicating on the phone. C1 [Gladd, Dana K.; Saunders, Gabrielle H.] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR USA. RP Gladd, DK (reprint author), 3710 SW US Vet Hosp Rd NCRAR, Portland, OR 97239 USA. EM dana.koltenuk@gmail.com FU NIH [T35 DC008764]; VA RR and D Grant [C4844C] FX Support for this work was provided by NIH Predoctoral Training Grant T35 DC008764 and VA RR and D Grant # C4844C. We thank Patricia Pulliam, A.N.P., and other staff and patients of the Portland VA Medical Center Chemotherapy outpatient clinic for their participation, Roger Ellingson for his assistance with the equipment and Sarah Weidman for her assistance with data collection. NR 19 TC 4 Z9 4 U1 0 U2 2 PU MEDKNOW PUBLICATIONS PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1463-1741 J9 NOISE HEALTH JI Noise Health PD NOV-DEC PY 2011 VL 13 IS 55 BP 444 EP 451 DI 10.4103/1463-1741.90322 PG 8 WC Audiology & Speech-Language Pathology; Public, Environmental & Occupational Health SC Audiology & Speech-Language Pathology; Public, Environmental & Occupational Health GA 855WE UT WOS:000297596000010 PM 22122961 ER PT J AU Tang, PA Heng, DYC Choueiri, TK AF Tang, Patricia A. Heng, Daniel Y. C. Choueiri, Toni K. TI Impact of Body Composition on Clinical Outcomes in Metastatic Renal Cell Cancer SO ONCOLOGIST LA English DT Editorial Material ID MASS INDEX; CARCINOMA; OBESITY; SORAFENIB; TRIALS; TUMORS; RISK C1 [Tang, Patricia A.; Heng, Daniel Y. C.] Univ Calgary, Tom Baker Canc Ctr, Dept Oncol, Calgary, AB T2N 4N2, Canada. [Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA USA. RP Tang, PA (reprint author), Univ Calgary, Tom Baker Canc Ctr, Dept Oncol, 1331 29 St NW, Calgary, AB T2N 4N2, Canada. EM patricia.tang@albertahealthservices.ca RI Inov Farmaceutica, Inct/K-2313-2013 NR 26 TC 6 Z9 6 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD NOV PY 2011 VL 16 IS 11 BP 1484 EP 1486 DI 10.1634/theoncologist.2011-0337 PG 3 WC Oncology SC Oncology GA 859EZ UT WOS:000297860900002 PM 22020214 ER PT J AU Kwak, E AF Kwak, Eunice TI The Role of Irreversible HER Family Inhibition in the Treatment of Patients with Non-Small Cell Lung Cancer SO ONCOLOGIST LA English DT Article DE Irreversible EGFR/HER-2 tyrosine kinase inhibitors; Non-small cell lung cancer; Resistance; Afatinib (BIBW 2992); PF00299804 ID EPIDERMAL-GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; PHASE-III TRIAL; PREVIOUSLY TREATED PATIENTS; ADVANCED SOLID TUMORS; BIBW 2992; RESISTANCE MUTATION; ACQUIRED-RESISTANCE; 1ST-LINE GEFITINIB; RANDOMIZED-TRIAL AB Small-molecule tyrosine kinase inhibitors (TKIs) of the human epidermal growth factor receptor (HER) include the reversible epidermal growth factor receptor (EGFR/HER-1) inhibitors gefitinib and erlotinib. EGFR TKIs have demonstrated activity in the treatment of patients with non-small cell lung cancer (NSCLC) harboring activating EGFR mutations; however, multiple mechanisms of resistance limit the benefit of these drugs. Although resistance to EGFR TKIs can be intrinsic and correlated with molecular lesions such as in Kirsten rat sarcoma viral oncogene homolog (KRAS; generally observed in a wild-type EGFR background), acquired resistance to EGFR TKIs can evolve in the setting of activating EGFR mutations, such as in the case of EGFR T790M mutations. Several irreversible inhibitors that target multiple members of the HER family simultaneously are currently in clinical development for NSCLC and may have a role in the treatment of TKI-sensitive and TKI-resistant disease. These include PF00299804, an inhibitor of EGFR/HER-1, HER-2, and HER-4, and afatinib (BIBW 2992), an inhibitor of EGFR/HER-1, HER-2, and HER-4. Results of large, randomized trials of these agents may help to determine their potential for the treatment of NSCLC. The Oncologist 2011; 16: 1498-1507 C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Kwak, E (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,YAW 7, Boston, MA 02114 USA. EM ekwak@partners.org RI Inov Farmaceutica, Inct/K-2313-2013; Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 FU Boehringer Ingelheim Pharmaceuticals, Inc (BIPI) FX This work was supported by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI). The author received no compensation related to the development of the manuscript. NR 87 TC 29 Z9 29 U1 0 U2 7 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD NOV PY 2011 VL 16 IS 11 BP 1498 EP 1507 DI 10.1634/theoncologist.2011-0087 PG 10 WC Oncology SC Oncology GA 859EZ UT WOS:000297860900004 PM 22016476 ER PT J AU Chan, CC Rubenstein, JL Coupland, SE Davis, JL Harbour, JW Johnston, PB Cassoux, N Touitou, V Smith, JR Batchelor, TT Pulido, JS AF Chan, Chi-Chao Rubenstein, James L. Coupland, Sarah E. Davis, Janet L. Harbour, J. William Johnston, Patrick B. Cassoux, Nathalie Touitou, Valerie Smith, Justine R. Batchelor, Tracy T. Pulido, Jose S. TI Primary Vitreoretinal Lymphoma: A Report from an International Primary Central Nervous System Lymphoma Collaborative Group Symposium SO ONCOLOGIST LA English DT Article ID PRIMARY INTRAOCULAR LYMPHOMA; PRIMARY CNS LYMPHOMA; B-CELL LYMPHOMA; ATTRACTING CHEMOKINE-1 CXCL13; POLYMERASE-CHAIN-REACTION; NON-HODGKINS-LYMPHOMA; INTRAVITREAL METHOTREXATE; MALIGNANT-LYMPHOMA; GENE-EXPRESSION; RITUXIMAB INJECTIONS AB Primary vitreoretinal lymphoma (PVRL), also known as primary intraocular lymphoma, is a rare malignancy typically classified as a diffuse large B-cell lymphoma and most frequently develops in elderly populations. PVRL commonly masquerades as posterior uveitis and has a unique tropism for the retina and central nervous system (CNS). Over 15% of primary CNS lymphoma patients develop intraocular lymphoma, usually occurring in the retina and/or vitreous. Conversely, 65%-90% of PVRL patients develop CNS lymphoma. Consequently, PVRL is often fatal because of ultimate CNS association. Current PVRL animal models are limited and require further development. Typical clinical findings include vitreous cellu-lar infiltration (lymphoma and inflammatory cells) and subretinal tumor infiltration as determined using dilated fundoscopy, fluorescent angiography, and optical coherent tomography. Currently, PVRL is most often diagnosed using both histology to identify lymphoma cells in the vitreous or retina and immunohistochemistry to indicate monoclonality. Additional adjuncts in diagnosing PVRL exist, including elevation of interleukin-10 levels in ocular fluids and detection of Ig H or T-cell receptor gene rearrangements in malignant cells. The optimal therapy for PVRL is not defined and requires the combined effort of oncologists and ophthalmologists. PVRL is sensitive to radiation therapy and exhibits high responsiveness to intravitreal methotrexate or rituximab. Although systemic chemotherapy alone can result in high response rates in patients with PVRL, there is a high relapse rate. Because of the disease rarity, international, multicenter, collaborative efforts are required to better understand the biology and pathogenesis of PVRL as well as to define both diagnostic markers and optimal therapies. The Oncologist 2011;16:1589-1599 C1 [Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Rubenstein, James L.] Univ Calif San Francisco, Sch Med, Div Hematol & Oncol, San Francisco, CA USA. [Coupland, Sarah E.] Royal Liverpool Hosp, Dept Cell & Mol Pathol, Liverpool L7 8XP, Merseyside, England. [Davis, Janet L.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA. [Johnston, Patrick B.] Mayo Clin, Dept Hematol & Internal Med, Rochester, MN USA. [Pulido, Jose S.] Mayo Clin, Dept Ophthalmol, Rochester, MN USA. [Harbour, J. William] Washington Univ, Sch Med, Barnes Retina Inst, Ocular Oncol Serv, St Louis, MO USA. [Cassoux, Nathalie; Touitou, Valerie] Hop La Pitie Salpetriere, Dept Ophthalmol, Paris, France. [Cassoux, Nathalie] Inst Curie, Dept Ophthalmol, Paris, France. [Smith, Justine R.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Batchelor, Tracy T.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Batchelor, Tracy T.] Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov RI Inov Farmaceutica, Inct/K-2313-2013 FU Novartis; Genentech; NIH; Pfizer; Millennium; AstraZeneca; Wyeth; National Cancer Institute [1R13CA124293-01]; National Eye Institute FX Disclosures: Chi-Chao Chan: None; James L. Rubenstein: None; Sarah E. Coupland: None; Janet L. Davis: Centocor (C/A), Novartis (C/A, RF); J. William Harbour: None; Patrick B. Johnston: Daiichi Sankyo, Spectrum Pharmaceutical (C/A); Nathalie Cassoux: None; Valerie Touitou: None; Justine R. Smith: Genentech (RF); Tracy T. Batchelor: Merck, Roche/Genentech, Imedex, Educational Concepts (H); NIH, Pfizer, Millennium, AstraZeneca, Wyeth (RF); Jose S. Pulido: None.; This work was partially supported by a grant from the National Cancer Institute (1R13CA124293-01) and the National Eye Institute intramural research program. NR 94 TC 80 Z9 87 U1 2 U2 8 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD NOV PY 2011 VL 16 IS 11 BP 1589 EP 1599 DI 10.1634/theoncologist.2011-0210 PG 11 WC Oncology SC Oncology GA 859EZ UT WOS:000297860900015 PM 22045784 ER PT J AU Niederman, R Richards, D AF Niederman, Richard Richards, Derek TI What is Evidence-Based Dentistry, and Do Oral Infections Increase Systemic Morbidity or Mortality? SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Evidence-based dentistry; Oral infections; Molecular medicine; Inflammation ID LOW-BIRTH-WEIGHT; DISEASE; THERAPY; HEALTH; TEETH; RISK AB From Celsus' first reports of rubor, calor, dolor, tumor, and functio laesa, has come an understanding of inflammation's manifestations at the organ, tissue, vascular, cellular, genetic, and molecular levels. Molecular medicine now raises the opposite question: can local oral infections and their inflammatory mediators increase systemic morbidity or mortality? From these perspectives we examine the clinical evidence relating caries, periodontal disease, and pericoronitis to systemic disease. Widespread affirmation of an oral-systemic linkage remains elusive, raising sobering cautions. C1 [Niederman, Richard] Forsyth Inst, Ctr Evidence Based Dent, Cambridge, MA 02142 USA. [Richards, Derek] Univ Oxford, Ctr Evidence Based Dent, Oxford OX1 2JA, England. RP Niederman, R (reprint author), Forsyth Inst, Ctr Evidence Based Dent, 245 1st St, Cambridge, MA 02142 USA. EM rniederman1@gmail.com OI niederman, richard/0000-0001-6674-1774 NR 29 TC 1 Z9 1 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1042-3699 J9 ORAL MAXIL SURG CLIN JI Oral Maxillofac. Surg. Clin. N. Am. PD NOV PY 2011 VL 23 IS 4 BP 491 EP + DI 10.1016/j.coms.2011.07.001 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 856DJ UT WOS:000297616900002 PM 21982600 ER PT J AU Susarla, SM Sharaf, B Dodson, TB AF Susarla, Srinivas M. Sharaf, Basel Dodson, Thomas B. TI Do Antibiotics Reduce the Frequency of Surgical Site Infections After Impacted Mandibular Third Molar Surgery? SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Third molars; Antibiotics; Surgical site infection; Impacted teeth ID CONTROLLED CLINICAL-TRIAL; INFLAMMATORY COMPLICATIONS; PROPHYLACTIC ANTIBIOTICS; PREVENTION; REMOVAL; METRONIDAZOLE; CLINDAMYCIN; TINIDAZOLE; NECESSITY; OPINION AB Surgical removal of impacted third molars remains the most common procedure performed by oral and maxillofacial surgeons. Given the abundance of host bacteria within the operative sites, surgical site infections are among the most common complications of third molar removal, with an estimated frequency of 1% to 30%. In this setting, significant controversy has surrounded the use of prophylactic antibiotics in the surgical management of impacted third molars. This article provides a comprehensive review of the available data on antibiotic prophylaxis in impacted third molar surgery and offers specific recommendations on antibiotic use. C1 [Susarla, Srinivas M.; Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Investigat, Boston, MA 02114 USA. [Sharaf, Basel] SUNY Buffalo, Buffalo Gen Hosp, Sch Med & Biomed Sci, Dept Surg, Buffalo, NY 14203 USA. RP Susarla, SM (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Investigat, 55 Fruit St,WACC230, Boston, MA 02114 USA. EM smsusarla@gmail.com OI Susarla, Srinivas/0000-0003-0155-8260 NR 29 TC 10 Z9 10 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1042-3699 J9 ORAL MAXIL SURG CLIN JI Oral Maxillofac. Surg. Clin. N. Am. PD NOV PY 2011 VL 23 IS 4 BP 541 EP + DI 10.1016/j.coms.2011.07.007 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 856DJ UT WOS:000297616900008 PM 21982606 ER PT J AU Sharaf, B Dodson, TB AF Sharaf, Basel Dodson, Thomas B. TI Does the Use of Prophylactic Antibiotics Decrease Implant Failure? SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Prophylactic antibiotics; Implant dentistry; Implant failure; Dental implants ID RANDOMIZED CLINICAL-TRIAL; DENTAL IMPLANTS; PERIOPERATIVE ANTIBIOTICS; ORAL IMPLANTS; SURGERY; PLACEMENT AB The use of prophylactic antibiotics in implant dentistry is controversial. Given the known risks of antibiotic treatment and lack of consensus on using antibiotics at the time of implant insertion, the purpose of this article was to review available studies on use of perioperative prophylactic antibiotics at the time of implant placement and to provide evidence-based recommendations for antibiotic use. The reviewed studies suggest that a single preoperative dose of 2 g amoxicillin 1 hour before implant placement or 1 g amoxicillin 1 hour preoperatively and 500 mg 4 times daily 2 days postoperatively can reduce the rate of implant failure. C1 [Sharaf, Basel] SUNY Buffalo, Buffalo Gen Hosp, Dept Surg, Sch Med & Biomed Sci, Buffalo, NY 14203 USA. [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Ctr Appl Clin Investigat, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Dodson, Thomas B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sharaf, B (reprint author), SUNY Buffalo, Buffalo Gen Hosp, Dept Surg, Sch Med & Biomed Sci, 100 High St,Room C381, Buffalo, NY 14203 USA. EM sharafddsmd@gmail.com NR 12 TC 2 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 1042-3699 J9 ORAL MAXIL SURG CLIN JI Oral Maxillofac. Surg. Clin. N. Am. PD NOV PY 2011 VL 23 IS 4 BP 547 EP + DI 10.1016/j.coms.2011.07.008 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 856DJ UT WOS:000297616900009 PM 21982607 ER PT J AU Palmason, S Marty, FM Treister, NS AF Palmason, Stefan Marty, Francisco M. Treister, Nathaniel S. TI How Do We Manage Oral Infections in Allogeneic Stem Cell Transplantation and Other Severely Immunocompromised Patients? SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Immunocompromise; Neutropenia; Infection; Odontogenic; Oral ID HERPES-SIMPLEX-VIRUS; BONE-MARROW-TRANSPLANTATION; EPSTEIN-BARR-VIRUS; VARICELLA-ZOSTER-VIRUS; POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDER; INVASIVE FUNGAL-INFECTIONS; LIPOSOMAL AMPHOTERICIN-B; PLACEBO-CONTROLLED TRIAL; BLOOD-STREAM INFECTIONS; RANDOMIZED DOUBLE-BLIND AB The oral cavity is among the sites in the body most susceptible to infections. In the immunocompetent population these are most frequently localized odontogenic infections caused by bacteria. In severely immunocompromised patients, such as those undergoing allogeneic stem cell transplantation, fungal and viral infections become especially prominent. Infections in this population can present in an unusual fashion, can spread rapidly to other organs in the body, and are more frequently resistant to therapies. This article discusses the current knowledge of the most frequent presentations of infections in this patient population and reviews contemporary approaches to prevention, diagnosis, and management. C1 [Palmason, Stefan; Treister, Nathaniel S.] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02120 USA. [Palmason, Stefan; Treister, Nathaniel S.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Marty, Francisco M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Infect Dis,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Palmason, S (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 1620 Tremont St, Boston, MA 02120 USA. EM spalmason@partners.org NR 204 TC 3 Z9 3 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 1042-3699 J9 ORAL MAXIL SURG CLIN JI Oral Maxillofac. Surg. Clin. N. Am. PD NOV PY 2011 VL 23 IS 4 BP 579 EP + DI 10.1016/j.coms.2011.07.012 PG 22 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 856DJ UT WOS:000297616900013 PM 21982611 ER PT J AU Khan, S Lefevre, J Ammari, H Baillet, S AF Khan, Sheraz Lefevre, Julien Ammari, Habib Baillet, Sylvain TI Feature detection and tracking in optical flow on non-flat manifolds SO PATTERN RECOGNITION LETTERS LA English DT Article DE Optical flow; Helmholtz-Hodge decomposition; Feature detection; Image processing; Riemannian formalism; Vector fields ID HODGE-HELMHOLTZ DECOMPOSITION; FIELD DECOMPOSITION; MOTION FIELDS AB Optical flow is a classical approach to estimating the velocity vector fields associated to illuminated objects traveling onto manifolds. The extraction of rotational (vortices) or curl-free (sources or sinks) features of interest from these vector fields can be obtained from their Helmholtz-Hodge decomposition (HHD). However, the applications of existing HHD techniques are limited to flat, 2D domains. Here we demonstrate the extension of the HHD to vector fields defined over arbitrary surface manifolds. We propose a Riemannian variational formalism, and illustrate the proposed methodology with synthetic and empirical examples of optical-flow vector field decompositions obtained on a variety of surface objects. (C) 2011 Elsevier B.V. All rights reserved. C1 [Khan, Sheraz; Baillet, Sylvain] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. [Lefevre, Julien] Aix Marseille Univ, Dept Informat Luminy CNRS, LSIS, UMR 6168, F-13397 Marseille, France. [Khan, Sheraz; Ammari, Habib] Ecole Polytech, Ctr Appl Math, F-91128 Palaiseau, France. [Khan, Sheraz] MGH Harvard Med Sch, Dept Neurol, Boston, MA USA. [Baillet, Sylvain] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. RP Khan, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. EM sheraz@nmr.mgh.harvard.edu RI Lefevre, Julien/G-1789-2013; OI Khan, Sheraz/0000-0002-6792-3577 NR 16 TC 3 Z9 3 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8655 J9 PATTERN RECOGN LETT JI Pattern Recognit. Lett. PD NOV 1 PY 2011 VL 32 IS 15 BP 2047 EP 2052 DI 10.1016/j.patrec.2011.09.017 PG 6 WC Computer Science, Artificial Intelligence SC Computer Science GA 859OO UT WOS:000297885900013 ER PT J AU New, AS AF New, Antonia S. TI Partial Success? SO PERSONALITY AND MENTAL HEALTH LA English DT Editorial Material ID PERSONALITY-DISORDER; DSM-IV C1 [New, Antonia S.] Mt Sinai Sch Med, New York, NY USA. [New, Antonia S.] James J Peters VAMC, Mental Illness Res Educ & Clin Care Ctr, Bronx, NY USA. RP New, AS (reprint author), Mt Sinai Sch Med, New York, NY USA. EM antonia.new@mssm.edu NR 4 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1932-8621 J9 PERSONAL MENT HEALTH JI Personal. Ment. Health PD NOV PY 2011 VL 5 IS 4 SI SI BP 301 EP 303 DI 10.1002/pmh.188 PG 3 WC Psychiatry; Psychology, Social SC Psychiatry; Psychology GA 854OS UT WOS:000297504700010 ER PT J AU Zhang, F Wang, SP Gan, L Vosler, PS Gao, YQ Zigmond, MJ Chen, J AF Zhang, Feng Wang, Suping Gan, Li Vosler, Peter S. Gao, Yanqin Zigmond, Michael J. Chen, Jun TI Protective effects and mechanisms of sirtuins in the nervous system SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE SIRT1; Deacetylation; Cell death; Cerebral ischemia; Neurodegenerative disease; Neuroprotection ID NF-KAPPA-B; GLOBAL CEREBRAL-ISCHEMIA; OXYGEN-GLUCOSE DEPRIVATION; ACTIVATED RECEPTOR-ALPHA; NITRIC-OXIDE SYNTHASE; BASE-EXCISION-REPAIR; FATTY-ACID OXIDATION; SIR2 HISTONE/PROTEIN DEACETYLASES; AMYOTROPHIC-LATERAL-SCLEROSIS; STRESS-RESPONSIVE DEACETYLASE AB Silent information regulator two proteins (sirtuins or SIRTs) are a group of histone deacetylases whose activities are dependent on and regulated by nicotinamide adenine dinucleotide (NAD(+)). They suppress genome-wide transcription, yet upregulate a select set of proteins related to energy metabolism and pro-survival mechanisms, and therefore play a key role in the longevity effects elicited by calorie restriction. Recently, a neuroprotective effect of sirtuins has been reported for both acute and chronic neurological diseases. The focus of this review is to summarize the latest progress regarding the protective effects of sirtuins, with a focus on SIRT1. We first introduce the distribution of sirtuins in the brain and how their expression and activity are regulated. We then highlight their protective effects against common neurological disorders, such as cerebral ischemia, axonal injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Finally, we analyze the mechanisms underlying sirtuin-mediated neuroprotection, centering on their non-histone substrates such as DNA repair enzymes, protein kinases, transcription factors, and coactivators. Collectively, the information compiled here will serve as a comprehensive reference for the actions of sirtuins in the nervous system to date, and will hopefully help to design further experimental research and expand sirtuins as therapeutic targets in the future. Published by Elsevier Ltd. C1 [Zhang, Feng; Wang, Suping; Vosler, Peter S.; Gao, Yanqin; Zigmond, Michael J.; Chen, Jun] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Zhang, Feng; Wang, Suping; Gao, Yanqin; Zigmond, Michael J.; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. [Zhang, Feng; Wang, Suping; Gao, Yanqin; Zigmond, Michael J.; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200032, Peoples R China. [Gan, Li] Univ Calif San Francisco, Gladstone Inst Neurol Dis, Dept Neurol, San Francisco, CA 94158 USA. [Zhang, Feng; Wang, Suping; Vosler, Peter S.; Gao, Yanqin; Zigmond, Michael J.; Chen, Jun] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. EM zhanfx2@upmc.edu; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819 FU Chinese Ministry of Science Technology; National Institutes of Health [NS36736, NS43802, NS45048, NS62157]; American Heart Association [10SDG2560122] FX This work was supported by Special Research Funds from Chinese Ministry of Science & Technology to State Key laboratories (Y. G., M. Z., and J.C.), grants from the National Institutes of Health (NS36736, NS43802, NS45048 and NS62157 to J.C.), and the American Heart Association (10SDG2560122 to F.Z.). We thank Pat Strickler for secretarial support and Carol Culver for editorial assistance. NR 327 TC 69 Z9 74 U1 2 U2 31 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD NOV PY 2011 VL 95 IS 3 BP 373 EP 395 DI 10.1016/j.pneurobio.2011.09.001 PG 23 WC Neurosciences SC Neurosciences & Neurology GA 856CJ UT WOS:000297614000005 PM 21930182 ER PT J AU Kacmarek, RM AF Kacmarek, Robert M. TI Ventilator Software Version Markedly Affects Time to Trigger and Time Delay respond SO RESPIRATORY CARE LA English DT Letter C1 Massachusetts Gen Hosp, Resp Care Dept, Boston, MA 02114 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Dept, Boston, MA 02114 USA. NR 0 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 NOV PY 2011 VL 56 IS 11 BP 1867 EP 1867 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 859TQ UT WOS:000297899100024 ER PT J AU Nigwekar, SU Waikar, SS AF Nigwekar, Sagar U. Waikar, Sushrut S. TI Diuretics in Acute Kidney Injury SO SEMINARS IN NEPHROLOGY LA English DT Review DE Acute kidney injury; diuretics; fenoldopam; natriuretic peptides ID ACUTE-RENAL-FAILURE; CRITICALLY-ILL PATIENTS; ATRIAL-NATRIURETIC-PEPTIDE; ACUTE TUBULAR-NECROSIS; INTENSIVE-CARE-UNIT; HIGH-DOSE FRUSEMIDE; LOOP DIURETICS; DOUBLE-BLIND; CARDIAC-SURGERY; REPLACEMENT THERAPY AB Acute kidney injury (AKI) is common in hospitalized patients and is associated with significant morbidity and mortality. The incidence of AKI is increasing and despite clinical advances there has been little change in the outcomes associated with AKI. A variety of interventions, including loop diuretics, have been tested for the prevention and treatment of AKI; however, none to date have shown convincing benefits in clinical studies, and the management of AKI remains largely supportive. In this article, we review the pharmacology and experimental and clinical evidence for loop diuretics in the management of AKI. In addition, we also review evidence for other agents with diuretic and/or natriuretic properties such as thiazide diuretics, mannitol, fenoldopam, and natriuretic peptides in both the prevention and treatment of AKI. Implications for current clinical practice are outlined to guide clinical decisions in this field. Semin Nephrol 31:523-534 (C) 2011 Elsevier Inc. All rights reserved. C1 [Nigwekar, Sagar U.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Waikar, Sushrut S.] Harvard Univ, Sch Med, Scholars Clin Sci Program, Boston, MA USA. RP Nigwekar, SU (reprint author), Massachusetts Gen Hosp, Div Nephrol, 55 Fruit St,Bulfinch 127, Boston, MA 02114 USA. EM sagarnigs@gmail.com NR 129 TC 6 Z9 8 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD NOV PY 2011 VL 31 IS 6 BP 523 EP 534 DI 10.1016/j.semnephrol.2011.09.007 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 858FI UT WOS:000297780900007 PM 22099509 ER PT J AU Lebl, DR Bono, CM Metkar, US Grottkau, BE Wood, KB AF Lebl, Darren R. Bono, Christopher M. Metkar, Umesh S. Grottkau, Brian E. Wood, Kirkham B. TI Bioabsorbable anterior cervical plate fixation for single-level degenerative disorders: early clinical and radiographic experience SO SPINE JOURNAL LA English DT Article DE Bioabsorbable; Cervical; Fusion; Spinal instrumentation ID BIOMECHANICAL EVALUATION; INTERBODY FUSION; SPINE; DISKECTOMY; COMPLICATIONS; STABILIZATION; ALLOGRAFT; OUTCOMES; IMPLANT; SCREW AB BACKGROUND CONTEXT: Increased fusion rates have been reported with the addition of an anterior cervical plate (ACP) to anterior cervical discectomy and fusion (ACDF). Bioabsorbable implants have become increasingly used in orthopedic and spine surgical procedures. There are limited data regarding the outcomes of bioabsorbable ACP (bACP) with ACDF. PURPOSE: To compare the clinical and radiographic outcomes of patients undergoing ACDF for single-level degenerative disorders with a bACP versus a conventional metal ACP (mACP). STUDY DESIGN: Retrospective comparative cohort study. PATIENT SAMPLE: Thirty-one patients undergoing ACDF for a single-level degenerative disorder (ie, disc herniation or spondylotic neural compression). OUTCOME MEASURES: Incidence of early (within 2 weeks) complications, postoperative sagittal alignment, Odom's criteria, and pseudarthrosis rate. METHODS: The authors retrospectively reviewed the results of a consecutive series of patients undergoing ACDF for symptomatic single-level disc herniation or spondylotic neural compression with either a bACP or an mACP over a 3-year period. Operative notes, clinical charts, and radiographs were analyzed. Radiographic outcomes were assessed for intersegmental alignment, graft subsidence, fusion rate, prevertebral soft-tissue shadow, and graft containment. Clinical outcome was evaluated by Odom's criteria. RESULTS: Fourteen patients underwent ACDF with a bACP and 15 with an mACP. Radiographic outcomes at the most recent follow-up demonstrated pseudarthrosis in 4 of 14 patients (29%) in the bACP group and 0 of 15 patients in the mACP group. Graft extrusion and anterior displacement was present in three of four pseudarthroses (75%). Comparing preoperative and final radiographs, cervical lordosis was maintained at the operative segment in only 3 of 14 bACP patients (21%) compared with 8 of 15 patients (53%) in the mACP group. The mean Cobb angle was 2.4 degrees +/- 1.9 degrees lordosis in the mACP group and -2.7 degrees +/- 2.5 degrees kyphosis in the bACP group (p=.12). In the mACP group, 14 of 15 patients had good or excellent results. In the bACP group, only 7 of 14 patients had good or excellent results. CONCLUSIONS: Bioabsorbable ACP fixation was associated with a high rate of graft extrusion and early loss of intersegmental cervical alignment. Inferior clinical outcomes were observed in patients in the bACP group compared with the mACP group. Based on these findings, continued use of the bACP used in this study cannot be recommended. (C) 2011 Elsevier Inc. All rights reserved. C1 [Metkar, Umesh S.; Grottkau, Brian E.; Wood, Kirkham B.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. [Lebl, Darren R.] Hosp Special Surg, New York, NY 10021 USA. [Bono, Christopher M.] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Wood, KB (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr Outpatient Care, 32 Fruit St, Boston, MA 02114 USA. EM kbwood@partners.org NR 29 TC 4 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 J9 SPINE J JI Spine Journal PD NOV PY 2011 VL 11 IS 11 BP 1002 EP 1008 DI 10.1016/j.spinee.2011.09.010 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 859GG UT WOS:000297864300003 PM 22000725 ER PT J AU Elfiky, AA Cho, DC McDermott, DF Rosenberg, JE Fortner, B Antras, L Chen, K Duh, MS Jayawant, SS Oh, WK Atkins, MB Choueiri, TK AF Elfiky, Aymen A. Cho, Daniel C. McDermott, David F. Rosenberg, Jonathan E. Fortner, Barry Antras, Lucia Chen, Kristina Duh, Mei Sheng Jayawant, Sujata S. Oh, William K. Atkins, Michael B. Choueiri, Toni K. TI Predictors of response to sequential sunitinib and the impact of prior VEGF-targeted drug washout in patients with metastatic clear-cell renal cell carcinoma SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Sunitinib; Sorafenib; Bevacizumab; Angiogenesis inhibitors; Sequential therapy ID ENDOTHELIAL GROWTH-FACTOR; PHASE-III TRIAL; PROGNOSTIC-FACTORS; ANTITUMOR-ACTIVITY; SORAFENIB; THERAPY; ANGIOGENESIS; PROGRESSION; RECEPTOR AB Objective: To identify factors that can be used to identify metastatic clear cell RCC patients more likely to benefit from sequential sunitinib. Patients and methods: We identified patients who failed sorafenib or bevacizumab and subsequently received sunitinib. We looked at objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) to sunitinib in relation to baseline clinical variables. Results: Seventy-one patients received sunitinib sequential therapy. Median duration of follow-up after starting sunitinib was 9.3 months. Median PFS was 5.8 months; median OS was not reached. Significantly higher ORR was seen in patients with normal hemoglobin (25.6%) [defined as >12 gm/dl for female; >13 gm/dl for male]. In addition, a shorter PFS for patients with low hemoglobin, and patients with time from diagnosis to first treatment <= 1 year was found. There was a shorter OS for patients >= 60 years old, with brain metastasis, low hemoglobin, and time from diagnosis to treatment <= 1 year. There was no difference in ORR, PFS, or OS in patients who started sunitinib after or within a 30-day period. Conclusions: Metastatic clear-cell RCC patients with anemia have less clinical benefit from sequential sunitinib after failure of bevacizumab or sorafenib. Other factors associated with poor outcome include brain metastases, older age, and <1 year between diagnosis and first treatment. Importantly, no difference in outcomes was observed if sequential therapy was initiated within or after 30 days. External validation and prospective evaluation are needed to confirm these findings. (C) 2011 Elsevier Inc. All rights reserved. C1 [Elfiky, Aymen A.; Cho, Daniel C.; McDermott, David F.; Rosenberg, Jonathan E.; Oh, William K.; Atkins, Michael B.; Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. [Fortner, Barry] P4 Healthcare, Lakeland, TN 38002 USA. [Antras, Lucia; Chen, Kristina; Duh, Mei Sheng; Jayawant, Sujata S.] Anal Grp Inc, Boston, MA 02115 USA. RP Choueiri, TK (reprint author), Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. EM Toni_Choueiri@dfci.harvard.edu FU DF/HCC Kidney Cancer SPORE FX This research was supported in part by the DF/HCC Kidney Cancer SPORE. NR 18 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV-DEC PY 2011 VL 29 IS 6 BP 756 EP 763 DI 10.1016/j.urolonc.2010.01.008 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 853RL UT WOS:000297443300025 PM 20451414 ER PT J AU Schutzer, WE Xue, H Reed, J Oyama, T Beard, DR Anderson, S Mader, SL AF Schutzer, William E. Xue, Hong Reed, John Oyama, Terry Beard, Douglas R. Anderson, Sharon Mader, Scott L. TI Age-related beta-adrenergic receptor-mediated vasorelaxation is changed by altering G protein receptor kinase 2 expression SO VASCULAR PHARMACOLOGY LA English DT Article DE Adenovirus; Adrenergic-beta; Aging; Fischer 344; Vasorelaxation; G protein receptor kinase (GRK) ID VASCULAR SMOOTH-MUSCLE; RAT AORTA; BETA(2)-ADRENERGIC RECEPTOR; BLOOD-PRESSURE; PLASMA-MEMBRANE; GENE-TRANSFER; DESENSITIZATION; MECHANISMS; RELAXATION; PHOSPHORYLATION AB Beta-adrenergic receptor- (beta-AR) mediated vasorelaxation declines with age. This change is likely related to receptor desensitization, rather than down regulation. One kinase responsible for desensitization is G protein receptor kinase 2 (GRK2). We have shown that GRK expression and activity increases with age in Fischer 344 rat aorta. In this study we validated that carotid arteries have similar age-related changes in the beta-AR signaling axis as aorta. This finding allowed use of in vivo infection and delivery of two adenovirus vectors to carotid arteries of 2-month-old (2 M) and 12-month-old (12 M) male Fischer 344 rats. Adeno-GRK2 was used to overexpress GRK2, and adeno-beta-ARK-ct was used to inhibit GRK2 function. Following a five-day infection, vessels were collected and ex vivo tissue bath was used to evaluate vasoreactivity. We used KCl contracted segments, and determined that overexpression of GRK2 significantly impaired isoproterenol (ISO)-mediated vasorelaxation in both age groups. Maximum relaxation (MA)() to ISO in vessels from 2 M decreased from 44% to 21%. MAX to ISO in vessels from 12 M decreased from 12% to 6%. Sensitivity (ED50) in vessels from 2 M and 12 M was also impaired 57%, and 30% respectively. We also determined that expression of adeno-beta-ARK-ct significantly improved ISO-mediated vasorelaxation in both age groups. MAX in vessels from 2 M increased from 44% to 58%. MAX in vessels from 12 M increased from 15% to 69%. ED50 in vessels from 2 M and 12 M was also improved 46%, and 50% respectively. These findings further implicate age-related increases in GRK2 expression as an important regulator of the age-related decline in beta-AR-mediated vasorelaxation. Published by Elsevier Inc. C1 [Schutzer, William E.; Xue, Hong; Reed, John; Oyama, Terry; Beard, Douglas R.; Anderson, Sharon; Mader, Scott L.] Portland VA Med Ctr, Res Serv, Portland, OR 97239 USA. [Schutzer, William E.; Anderson, Sharon; Mader, Scott L.] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97239 USA. RP Mader, SL (reprint author), Portland VA Med Ctr, Res Serv, RD26,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM scott.mader@va.gov FU Research Service, Department of Veterans Affairs FX This work was supported by the Research Service, Department of Veterans Affairs. We thank Mohammed Gaballa, PhD, Banner Sun Health Research Institute, Sun City, AZ for his guidance with the adenovirus delivery surgical procedures. NR 53 TC 5 Z9 5 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1537-1891 EI 1879-3649 J9 VASC PHARMACOL JI Vasc. Pharmacol. PD NOV-DEC PY 2011 VL 55 IS 5-6 BP 178 EP 188 DI 10.1016/j.vph.2011.09.001 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 858EF UT WOS:000297778000010 PM 21951806 ER PT J AU Weston, A Barton, C Lesselyong, J Yaffe, K AF Weston, Andrea Barton, Cynthia Lesselyong, Julia Yaffe, Kristine TI Functional deficits among patients with mild cognitive impairment SO ALZHEIMERS & DEMENTIA LA English DT Article DE Mild cognitive impairment; Dementia; Functional impairment; Instrumental activities of daily living; Activities of daily living ID DEMENTIA AB Background: Diagnostic criteria for mild cognitive impairment (MCI) include no significant functional decline, but recent studies have suggested that subtle deficits often exist. It is not known whether these differ by MCI type. We investigated the level and type of functional impairment among patients with MCI. Methods: We studied 498 patients, evaluated at the Alzheimer's Disease Research Centers of California between 2006 and 2009, who had multidisciplinary evaluations by experts, including neurologic examination and neuropsychological testing. Patients were diagnosed with MCI and subtype was determined using cognitive domain scores. In a cross-sectional descriptive study, we examined whether functional impairment differed by MCI subtype, using the Blessed Roth Dementia Rating Scale (range: 0-17, higher scores indicating more impairment). Results: Among the participants, the mean age was 75.4 years, 50.7% were women, and 81.7% were white. Patients with amnestic- (n = 392, 78.7%) and nonamnestic-type (n = 106, 21.3%) MCI had similar total Blessed Roth Dementia Rating Scale (1.6 and 1.5, respectively; P = .84) and MiniMental State Examination (26.5 and 26.7, respectively; P = .60) scores. Patients with amnestic MCI were more likely to have difficulty in remembering lists and recalling recent events (P < .05 for both) and less likely to have difficulty in eating and with continence (P = .01 for both), as compared with those with nonamnestic MCI. Conclusions: Despite the MCI diagnostic criteria suggesting no functional impairment, our results indicate that patients with MCI experience mild functional deficits that vary according to the type of MCI. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Weston, Andrea; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Weston, Andrea; Barton, Cynthia; Lesselyong, Julia; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Barton, Cynthia; Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Lesselyong, Julia] No Calif Inst Res & Educ, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Weston, A (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. EM andrea.weston@ucsf.edu FU National Institute of Aging [K24AG031155]; Mental Illness Research, Educational, and Clinical Cente; Sierra Pacific Veterans Integrated Service Network (VISN) Veteran's Administration FX Dr. Yaffe is supported in part by a Grant from the National Institute of Aging (K24AG031155) and by a Mental Illness Research, Educational, and Clinical Center Grant from the Sierra Pacific Veterans Integrated Service Network (VISN) Veteran's Administration. NR 15 TC 4 Z9 5 U1 0 U2 5 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 NOV PY 2011 VL 7 IS 6 BP 611 EP 614 DI 10.1016/j.jalz.2010.12.011 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 852WD UT WOS:000297387300008 PM 22055977 ER PT J AU Chou, SW Marousek, G Auerochs, S Stamminger, T Milbradt, J Marschall, M AF Chou, Sunwen Marousek, Gail Auerochs, Sabrina Stamminger, Thomas Milbradt, Jens Marschall, Manfred TI The unique antiviral activity of artesunate is broadly effective against human cytomegaloviruses including therapy-resistant mutants SO ANTIVIRAL RESEARCH LA English DT Article DE Human cytomegalovirus; Antiviral activity of artesunate; Artesunate-related drugs; Therapy-resistant virus mutants; Synergistic effect ID STEM-CELL TRANSPLANTATION; DRUG-RESISTANCE; MARIBAVIR; RECOMBINANT; REPLICATION; INFECTIONS; RECIPIENTS; MUTATIONS; POTENT AB Current therapy options to treat infections with human cytomegalovirus face severe limitations leading to a continued search for novel drug candidates. Here, we describe novel characteristics of the strong antiviral potency of the drug artesunate. In vitro virus replication systems were applied to analyze a number of laboratory and clinically relevant strains of human cytomegalovirus. An inhibitory block at a very early stage of infection was demonstrated. Time-of-addition experiments indicated that the antiviral efficacy could be optimized when artesunate was applied as fractional doses consecutively added post-infection. Artesunate showed a clearly higher anti-cytomegaloviral activity than its parental drug artemisinin (approximately 10-fold) or other artesunate-related compounds. Mean IC(50) values of artesunate for a variety of standard therapy-resistant virus mutants were within a 2-fold range compared to wild-type virus. Furthermore, a synergistic effect was identified when artesunate was combined with the mechanistically distinct antiviral compound maribavir. These findings point to unique antiviral properties of artesunate which may offer an advantage over standard antiviral therapy particularly in cases of drug resistance. (C) 2011 Published by Elsevier B.V. C1 [Auerochs, Sabrina; Stamminger, Thomas; Milbradt, Jens; Marschall, Manfred] Univ Erlangen Nurnberg, Inst Clin & Mol Virol, D-91054 Erlangen, Germany. [Chou, Sunwen] Oregon Hlth & Sci Univ, Div Infect Dis, Portland, OR 97201 USA. [Chou, Sunwen; Marousek, Gail] US Dept Vet Affairs, Med Ctr, Portland, OR USA. RP Marschall, M (reprint author), Univ Erlangen Nurnberg, Inst Clin & Mol Virol, Schlossgarten 4, D-91054 Erlangen, Germany. EM manfred.marschall@viro.med.uni-erlangen.de FU Department of Veterans Affairs (USA); Deutsche Forschungsgemeinschaft [MA 1289/7-1, SFB 796 C3/B3]; HHV-6 Foundation (Santa Barbara, CA, USA [M.M. 2009]; Bayerische Forschungsstiftung [4SC-2010] FX We like to thank Herwig Jansen (Dafra Pharma, Turhout, Belgium) and Duong Ngoc Ha (Saokim Pharma, Hanoi, Vietnam) for kindly providing ART, ART-related drugs and product information. We appreciate the cooperations with Thomas Efferth (Inst. Pharmacy and Biochem., Univ. Mainz, Germany) and Dana Wolf (Clin. Virol. Unit, Dept. Clin. Microbiol. Inf. Diseases, Hadassah Univ. Jerusalem, Israel) in the molecular and clinical evaluation of ART, respectively. This work was supported by the Department of Veterans Affairs (USA), Deutsche Forschungsgemeinschaft (Grant MA 1289/7-1 and SFB 796 C3/B3), HHV-6 Foundation (Santa Barbara, CA, USA, Grant M.M. 2009) and Bayerische Forschungsstiftung (Grant 4SC-2010). NR 26 TC 19 Z9 20 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD NOV PY 2011 VL 92 IS 2 BP 364 EP 368 DI 10.1016/j.antiviral.2011.07.018 PG 5 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 853LG UT WOS:000297427200027 PM 21843554 ER PT J AU Rehman, M Jenkins, KJ Juraszek, AL Connor, JA Gauvreau, K Muneeb, M Sena, LM Colan, SD Saia, T Kieran, MW AF Rehman, Maliha Jenkins, Kathy J. Juraszek, Amy L. Connor, Jean A. Gauvreau, Kimberlee Muneeb, Muhammad Sena, Laureen M. Colan, Steven D. Saia, Terry Kieran, Mark W. TI A Prospective Phase II Trial of Vinblastine and Methotrexate in Multivessel Intraluminal Pulmonary Vein Stenosis in Infants and Children SO CONGENITAL HEART DISEASE LA English DT Article DE Chemotherapy; PVS; Myofibroblasts ID LOW-DOSE CHEMOTHERAPY; DESMOID TUMOR; CONGENITAL STENOSIS; MYOFIBROMATOSIS; FIBROMATOSIS; CHILDHOOD; RECURRENT; REPAIR; BONE AB Objective. To determine the safety and efficacy of the chemotherapeutic agents vinblastine and methotrexate in the treatment of children with progressive multivessel intraluminal pulmonary vein stenosis (PVS). Methods. Children received weekly vinblastine and methotrexate for a period of 1 year. Outcomes (for patients receiving >= 1 month of chemotherapy) were classified separately for patients with isolated PVS and PVS with congenital heart disease (CHD). Primary efficacy outcome was "response to treatment" categorized by echocardiographic criteria of response. Survival to 1 year was also evaluated. All adverse events were classified according to Cancer Therapy Evaluation Program, Common Terminology Criteria version 3.0. Events were further classified as related to chemotherapy, cardiac, or other causes. Results. Among 29 patients enrolled, 28 received at least one dose of chemotherapy and were evaluable for toxicity, while 23 were evaluable for response (21 CHD, 2 isolated). Both patients in the isolated group had progressive disease and died. Overall, 33% (7/21) of patients with PVS and CHD had stable disease; 1-year survival of 38%; and four patients continue in remission (93, 96, 124, and 125 months after treatment initiation). While both cardiac-related (19%) and chemotherapy-related (53%) toxicities were common, most were asymptomatic laboratory changes. Grade 3 (13%) and grade 4 (4%) toxicities were reversible, and no treatment-related grade 5 toxicities were observed. Conclusion. We report on the first prospective trial of chemotherapy for infants and children targeting the presence of myofibroblastic cells within the lesions of PVS based on myofibroblastic proliferation associated with desmoid tumors of infancy. The toxicity profile resulted in numerous treatment delays and interruptions that, combined with limited information on the natural history of PVS in this patient population, hampered our ability to determine the true efficacy of this approach. These results will be important as a baseline for clinical trials in this patient population. C1 [Kieran, Mark W.] Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02215 USA. [Rehman, Maliha; Jenkins, Kathy J.; Connor, Jean A.; Gauvreau, Kimberlee; Muneeb, Muhammad; Colan, Steven D.; Saia, Terry] Childrens Hosp, Dept Cardiol, Boston, MA 02215 USA. [Sena, Laureen M.] Childrens Hosp, Dept Radiol, Boston, MA 02215 USA. [Juraszek, Amy L.] UT SW Med Ctr, Dept Pediat, Dallas, TX USA. [Juraszek, Amy L.] UT SW Med Ctr, Dept Pathol, Dallas, TX USA. RP Kieran, MW (reprint author), Dana Farber Canc Inst, Div Hematol Oncol, 450 Brookline Ave,Room SW331, Boston, MA 02215 USA. EM Mark_Kieran@dfci.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 NR 34 TC 10 Z9 10 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1747-079X J9 CONGENIT HEART DIS JI Congenit. Heart Dis. PD NOV-DEC PY 2011 VL 6 IS 6 BP 608 EP 623 DI 10.1111/j.1747-0803.2011.00574.x PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 853GF UT WOS:000297413500008 PM 22073909 ER PT J AU Haase, A Rigosi, E Frasnelli, E Trona, F Tessarolo, F Vinegoni, C Anfora, G Vallortigara, G Antolini, R AF Haase, Albrecht Rigosi, Elisa Frasnelli, Elisa Trona, Federica Tessarolo, Francesco Vinegoni, Claudio Anfora, Gianfranco Vallortigara, Giorgio Antolini, Renzo TI A multimodal approach for tracing lateralisation along the olfactory pathway in the honeybee through electrophysiological recordings, morpho-functional imaging, and behavioural studies SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Article DE Apis mellifera; Antennal lobe; Olfactory learning; Brain asymmetry; PER; SEM; EAG; Two-photon microscopy ID APIS-MELLIFERA; ANTENNAL LOBES; INSECT BRAIN; ODOR REPRESENTATION; NERVOUS-SYSTEM; NEURONS; MEMORY; BEE; MICROSCOPY; ADVANTAGES AB Recent studies have revealed asymmetries between the left and right sides of the brain in invertebrate species. Here we present a review of a series of recent studies from our laboratories, aimed at tracing asymmetries at different stages along the honeybee's (Apis mellifera) olfactory pathway. These include estimates of the number of sensilla present on the two antennae, obtained by scanning electron microscopy, as well as electroantennography recordings of the left and right antennal responses to odorants. We describe investigative studies of the antennal lobes, where multi-photon microscopy was used to search for possible morphological asymmetries between the two brain sides. Moreover, we report on recently published results obtained by two-photon calcium imaging for functional mapping of the antennal lobe aimed at comparing patterns of activity evoked by different odours. Finally, possible links to the results of behavioural tests, measuring asymmetries in single-sided olfactory memory recall, are discussed. C1 [Haase, Albrecht; Tessarolo, Francesco; Antolini, Renzo] Univ Trent, Dept Phys, I-38050 Povo, TN, Italy. [Haase, Albrecht; Tessarolo, Francesco; Antolini, Renzo] Univ Trent, Biotech Res Ctr, I-38050 Povo, TN, Italy. [Rigosi, Elisa; Vallortigara, Giorgio] Univ Trent, CIMeC, Ctr Mind Brain Sci, I-38068 Rovereto, Italy. [Rigosi, Elisa; Trona, Federica; Anfora, Gianfranco] Fdn Edmund Mach, Sustainable Agroecosyst & Bioresources Dept, IASMA Res & Innovat Ctr, I-38010 San Michele All Adige, TN, Italy. [Frasnelli, Elisa] Konrad Lorenz Inst Evolut & Cognit Res, A-3422 Altenberg, Austria. [Vinegoni, Claudio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Vinegoni, Claudio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Haase, A (reprint author), Univ Trent, Dept Phys, Via Sommarive 14, I-38050 Povo, TN, Italy. EM albrecht.haase@unitn.it RI Haase, Albrecht/H-4248-2012; OI Haase, Albrecht/0000-0002-8324-0047; ANFORA, Gianfranco/0000-0003-2545-1409 FU NIBIB NIH HHS [R01 EB006432, R01EB006432] NR 60 TC 7 Z9 8 U1 4 U2 22 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7571 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD NOV PY 2011 VL 40 IS 11 BP 1247 EP 1258 DI 10.1007/s00249-011-0748-6 PG 12 WC Biophysics SC Biophysics GA 852PX UT WOS:000297371000006 PM 21956452 ER PT J AU Toney, JH Stover, E AF Toney, Jeffrey H. Stover, Eric TI Retrospective: Richard Pierre Claude (1934-2011) SO HUMAN RIGHTS QUARTERLY LA English DT Biographical-Item C1 [Toney, Jeffrey H.] Kean Univ, Coll Nat Appl & Hlth Sci, Union, NJ 07083 USA. [Stover, Eric] Human Rights Ctr, Berkeley, CA USA. [Stover, Eric] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Stover, Eric] Amer Assoc Advancement Sci, Sci & Human Rights Program, Washington, DC USA. [Toney, Jeffrey H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Toney, Jeffrey H.] MIT, Cambridge, MA 02139 USA. [Toney, Jeffrey H.] Montclair State Univ, Montclair, NJ 07043 USA. RP Toney, JH (reprint author), Kean Univ, Coll Nat Appl & Hlth Sci, Union, NJ 07083 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0275-0392 J9 HUM RIGHTS QUART JI Hum. Rights Q. PD NOV PY 2011 VL 33 IS 4 BP 1195 EP 1197 PG 3 WC Political Science; Social Issues SC Government & Law; Social Issues GA 846YQ UT WOS:000296939500020 ER PT J AU Stange, JP Eisner, LR Holzel, BK Peckham, AD Dougherty, DD Rauch, SL Nierenberg, AA Lazar, S Deckersbach, T AF Stange, Jonathan P. Eisner, Lori R. Hoelzel, Britta K. Peckham, Andrew D. Dougherty, Darin D. Rauch, Scott L. Nierenberg, Andrew A. Lazar, Sara Deckersbach, Thilo TI Mindfulness-Based Cognitive Therapy for Bipolar Disorder: Effects on Cognitive Functioning SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE bipolar disorder; executive functioning; cognitive functioning; mindfulness; mindfulness-based cognitive therapy (MBCT); psychosocial treatment ID RANDOMIZED CONTROLLED-TRIAL; SHORT-TERM MEDITATION; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; TREATMENT ENHANCEMENT PROGRAM; FAMILY-FOCUSED TREATMENT; SOCIAL RHYTHM THERAPY; ANTERIOR CINGULATE; NEUROCOGNITIVE FUNCTION; RELAPSE PREVENTION; CORTICAL THICKNESS AB Bipolar disorder is associated with impairments in cognition, including difficulties in executive functioning, even when patients are euthymic (neither depressed nor manic). The purpose of this study was to assess changes in self-reported cognitive functioning in patients with bipolar disorder who participated in an open pilot trial of mindfulness-based cognitive therapy (MBCT). Following MBCT, patients reported significant improvements in executive functioning, memory, and ability to initiate and complete tasks, as measured by the Behavior Rating Inventory of Executive Function (BRIEF) and the Frontal Systems Behavior Scale (FrSBe). Changes in cognitive functioning were correlated with increases in mindful, nonjudgmental observance and awareness of thoughts, feelings, and sensations, and were not associated with decreases in depression. Improvements tended to diminish after termination of treatment, but some improvements, particularly those in executive functioning, persisted after 3 months. These results provide preliminary evidence that MBCT may be a treatment option that can be used as an adjunct to medication to improve cognitive functioning in bipolar disorder. (Journal of Psychiatric Practice 2011; 17: 410-419) C1 [Deckersbach, Thilo] Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Stange, Jonathan P.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Eisner, Lori R.; Dougherty, Darin D.; Nierenberg, Andrew A.; Lazar, Sara; Deckersbach, Thilo] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Hoelzel, Britta K.; Peckham, Andrew D.; Rauch, Scott L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [Hoelzel, Britta K.] Univ Giessen, D-35390 Giessen, Germany. [Peckham, Andrew D.; Rauch, Scott L.] McLean Hosp, Belmont, MA USA. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin & Res Program, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM tdeckersbach@partners.org RI Lazar, Sara/G-3809-2012 OI Lazar, Sara/0000-0003-1126-8363 FU NIMH [1K23MH074895-01A2]; European Community FX This work was supported by a K-23 NIMH Career Award 1K23MH074895-01A2 to Thilo Deckersbach. Part of this research was presented at the Association for Behavioral and Cognitive Therapies, San Francisco, 2010, and at the Ninth International Conference on Bipolar Disorder, Pittsburgh, 2011. Britta K. Holzel was supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme. NR 77 TC 26 Z9 26 U1 11 U2 48 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 NOV PY 2011 VL 17 IS 6 BP 410 EP 419 DI 10.1097/01.pra.0000407964.34604.03 PG 10 WC Psychiatry SC Psychiatry GA 853DM UT WOS:000297406400005 PM 22108398 ER PT J AU Rudolph, JL Harrington, MB Lucatorto, MA Chester, JG Francis, J Shay, KJ AF Rudolph, James L. Harrington, Mary Beth Lucatorto, Michelle A. Chester, Jennifer G. Francis, Joseph Shay, Kenneth J. CA Vet Affairs Delirium Working Grp TI Validation of a Medical Record-Based Delirium Risk Assessment SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE delirium; risk; hospitalization; quality measurement ID CONFUSION ASSESSMENT METHOD; ELDER-LIFE-PROGRAM; MINI-MENTAL-STATE; HIP FRACTURE; PREDICTION RULE; CARE; SURGERY; POPULATION; OUTCOMES; SYSTEM AB OBJECTIVES: To improve identification of patients at high risk for delirium, this study developed a chart abstraction tool for delirium risk and validated the tool against clinical expert diagnosis of delirium. DESIGN: Prospective cohort study. SETTING: Tertiary Veterans Affairs hospital in New England. PARTICIPANTS: One hundred veterans admitted to the medical service. MEASUREMENTS: While admitted, each participant underwent serial assessments for delirium by a clinical expert. Using the four criteria of a validated delirium prediction rule (cognitive impairment, sensory deficit, severe illness, and dehydration), chart review terms were selected for each criterion, and delirium risk was the sum of criteria present (range: 0-4; 4 = worst). After discharge, a nurse blinded to the expert's diagnosis completed the chart tool. RESULTS: The participants were mostly male (94%) and older (mean age 81 +/- 7), and 23% developed overall delirium (14% incident). The rate of overall delirium was 11% in participants with zero risk factors, 18% in those with one or two, and 50% in those with three or four (P = .01; c-statistic 0.65, 95% confidence interval (CI) = 0.54-0.76). For incident delirium, the rates were 11%, 13%, and 25%, respectively (P = .53; c-statistic 0.56, 95% CI = 0.42-0.74). Discharge to a rehabilitation center or nursing home increased with increasing delirium risk (0%, 18%, 60%, P = .02). CONCLUSION: A chart abstraction tool was effective at identifying overall delirium risk but not incident delirium risk. Although the tool cannot replace clinical assessment and diagnosis of delirium, the use of this tool as an educational, clinical, or quality measurement aid warrants additional study. J Am Geriatr Soc 59:S289-S294, 2011. C1 [Rudolph, James L.; Harrington, Mary Beth] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA 02130 USA. [Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Lucatorto, Michelle A.; Francis, Joseph] Vet Hlth Adm, Off Qual & Performance, Washington, DC USA. [Shay, Kenneth J.] Vet Hlth Adm, Off Geriatr Programs, Washington, DC USA. [Chester, Jennifer G.] Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Rudolph, JL (reprint author), VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. EM jrudolph@partners.org FU VA Rehabilitation Research Career Development Award; Einstein Research Fellowship; National Institutes of Health [AG026781-05, AG038027]; John A. Hartford Foundation FX Dr. Rudolph is supported by a VA Rehabilitation Research Career Development Award. Ms. Chester was funded by an Einstein Research Fellowship. Additional support was provided by the American Federation for Aging Research, the Boston Medical Student Training in Aging Research Program, and National Institutes of Health Grants AG026781-05 and AG038027. Drs. Rudolph, Harrington, Lucatorto, Shay, and Francis and the VADWG are VA employees. Publication was supported by the John A. Hartford Foundation. The authors maintained independence in the development, execution, and reporting of this study. The views and opinions expressed in this article are those of the authors and do not reflect or represent the official positions or policies of the U.S. Department of Veterans Affairs. NR 28 TC 14 Z9 14 U1 0 U2 8 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 NOV PY 2011 VL 59 SU 2 SI SI BP S289 EP S294 DI 10.1111/j.1532-5415.2011.03677.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 853FH UT WOS:000297411100012 PM 22091575 ER PT J AU Psaila, B Bussel, JB Frelinger, AL Babula, B Linden, MD Li, Y Barnard, MR Tate, C Feldman, EJ Michelson, AD AF Psaila, B. Bussel, J. B. Frelinger, A. L. Babula, B. Linden, M. D. Li, Y. Barnard, M. R. Tate, C. Feldman, E. J. Michelson, A. D. TI Differences in platelet function in patients with acute myeloid leukemia and myelodysplasia compared to equally thrombocytopenic patients with immune thrombocytopenia SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE autoimmunity; bleeding; flow cytometry; hemorrhage; thrombocytopenia; thrombopoiesis ID IB-IX COMPLEX; GLYCOPROTEIN IB; PURPURA ITP; IN-VITRO; AUTOANTIBODIES; REDISTRIBUTION; HETEROGENEITY; TRANSFUSIONS; HEMORRHAGE; PREDICTION AB Background: Severe thrombocytopenia is a major risk factor for hemorrhage, but platelet function and bleeding risk at low platelet counts are poorly understood, because of the limitations of platelet function testing at very low platelet counts. Objectives: To examine and compare platelet function in severely thrombocytopenic patients with acute myeloid leukemia(AML) ormyelodysplasia (MDS) with that in patients with immune thrombocytopenia (ITP). Methods: Whole blood flow cytometric measurement of platelet activation and platelet reactivity to agonists was correlated with the immature platelet fraction (IPF) and bleeding symptoms. Results: Patients with AML/MDS had smaller platelets, lower IPF and substantially lower platelet surface expression of activated glycoprotein (GP) IIb-IIIa and GPIb, both with and without addition of ex vivo ADP or thrombin receptor-activating peptide, than patients with ITP. In both ITP and AML/MDS patients, increased platelet surface GPIb on circulating platelets and expression of activated GPIIb-IIIa and GPIb on ex vivo activated platelets correlated with a higher IPF. Whereas platelet reactivity was higher for AML/MDS patients with bleeding than for those with no bleeding, platelet reactivity was lower for ITP patients with bleeding than for those with no bleeding. Conclusions: AML/MDS patients have lower in vivo platelet activation and ex vivo platelet reactivity than patients with ITP. The proportion of newly produced platelets correlates with the expression of platelet surface markers of activation. These differences might contribute to differences in bleeding tendency between AML/MDS and ITP patients. This study is the first to define differences in platelet function between AML/MDS patients and ITP patients with equivalent degrees of thrombocytopenia. C1 [Bussel, J. B.] Weill Cornell Med Coll, Dept Pediat, Platelet Disorders Ctr, Div Pediat Hematol Oncol, New York, NY 10021 USA. [Psaila, B.] Imperial Coll Sch Med, Dept Haematol, London, England. [Frelinger, A. L.; Linden, M. D.; Li, Y.; Barnard, M. R.; Michelson, A. D.] Univ Massachusetts, Sch Med, Dept Pediat, Ctr Platelet Funct Studies, Worcester, MA USA. [Frelinger, A. L.; Barnard, M. R.; Michelson, A. D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Platelet Res Studies,Div Hematol Oncol,Childr, Boston, MA 02115 USA. [Feldman, E. J.] Weill Cornell Med Coll, Div Hematol & Med Oncol, New York, NY 10021 USA. RP Bussel, JB (reprint author), Weill Cornell Med Coll, Dept Pediat, Platelet Disorders Ctr, Div Pediat Hematol Oncol, 525 E 68th St,P-695, New York, NY 10021 USA. EM jbussel@med.cornell.edu RI Linden, Matthew/G-9644-2012; OI Linden, Matthew/0000-0002-9126-2166; Psaila, Beth/0000-0001-8198-9663 FU GSK; Sysmex America Incorporated; Amgen; Cangene; GlaxoSmithKline; Genzyme; IgG of America; Immunomedics; Ligand; Eisai, Inc.; Shionogi; Sysmex FX This study was supported in part by research funding from GSK and Sysmex America Incorporated. Bussel currently receives clinical research support from the following companies: Amgen, Cangene, GlaxoSmithKline, Genzyme, IgG of America, Immunomedics, Ligand, Eisai, Inc., Shionogi, and Sysmex. J. B. Bussel's family owns stock in Amgen and GlaxoSmithKline, and he has participated in Advisory Boards and/or consults for Amgen, GlaxoSmithKline, Ligand, Shionogi, Eisai, and Portola. The services of M. Lesser and M. Fine were funded in part by GlaxoSmithKline. NR 29 TC 26 Z9 32 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD NOV PY 2011 VL 9 IS 11 BP 2302 EP 2310 DI 10.1111/j.1538-7836.2011.04506.x PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 851SS UT WOS:000297291800021 PM 21920014 ER PT J AU Stepp, CE Heaton, JT Stadelman-Cohen, TK Braden, MN Jette, ME Hillman, RE AF Stepp, Cara E. Heaton, James T. Stadelman-Cohen, Tara K. Braden, Maia N. Jette, Marie E. Hillman, Robert E. TI Characteristics of Phonatory Function in Singers and Nonsingers With Vocal Fold Nodules SO JOURNAL OF VOICE LA English DT Article DE Vocal hyperfunction; Vocal nodules; Neck surface electromyography ID LARYNGEAL MUSCLE-ACTIVITY; TENSION DYSPHONIA; VOICE ONSET; FREQUENCY; ELECTROMYOGRAPHY; DIAGNOSIS; PRESSURE; SPEAKERS; POLYPS AB Purpose. The goals of this study were to determine if there were significant differences between singers and nonsingers in the morphology of vocal nodules and the associated impact on vocal function. Method. Participants were 10 professionally trained singers with nodules, eight nonsingers with nodules, and 10 individuals with healthy normal voice (controls). Surface electromyography (sEMG) from three anterior neck locations and acoustic rise times for vowels /a/ and /i/ were measured in all the participants. In individuals with nodules, dB SPL/cm H2O, glottal airflow, and nodule location and size were also measured. Results. There were no significant differences between singers and nonsingers with nodules in terms of airflow, dB SPL/cm H2O, nodule size, or nodule location. In nonsingers with nodules, airflow and nodule size were significantly correlated, but were not significantly correlated in singers. Vowel rise times and sEMG during vocal tasks did not differentiate among nodule and control groups. Sternocleidomastoid sEMG during initiation of the vowel /a/ was statistically significantly stronger in nonsingers with nodules relative to singers with nodules and controls. Conclusions. Nodule morphology did not differ between singers and nonsingers, although some behavioral aspects of phonation differed between the groups. C1 [Stepp, Cara E.; Hillman, Robert E.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. [Stepp, Cara E.; Heaton, James T.; Stadelman-Cohen, Tara K.; Braden, Maia N.; Jette, Marie E.; Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Heaton, James T.; Hillman, Robert E.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Heaton, James T.; Stadelman-Cohen, Tara K.; Hillman, Robert E.] MGH Inst Hlth Profess, Sch Hlth & Rehabil Sci, Boston, MA USA. RP Stepp, CE (reprint author), Univ Washington, Box 352350, Seattle, WA 98195 USA. EM cstepp@alum.mit.edu OI Jette, Marie/0000-0003-4705-1289 FU NIDCD NIH HHS [T32 DC000038-20, T32 DC000038] NR 34 TC 3 Z9 4 U1 1 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0892-1997 J9 J VOICE JI J. Voice PD NOV PY 2011 VL 25 IS 6 BP 714 EP 724 DI 10.1016/j.jvoice.2010.06.003 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA 851NZ UT WOS:000297279100011 PM 21216129 ER PT J AU Fischer, SEJ Montgomery, TA Zhang, C Fahlgren, N Breen, PC Hwang, A Sullivan, CM Carrington, JC Ruvkun, G AF Fischer, Sylvia E. J. Montgomery, Taiowa A. Zhang, Chi Fahlgren, Noah Breen, Peter C. Hwang, Alexia Sullivan, Christopher M. Carrington, James C. Ruvkun, Gary TI The ERI-6/7 Helicase Acts at the First Stage of an siRNA Amplification Pathway That Targets Recent Gene Duplications SO PLOS GENETICS LA English DT Article ID CAENORHABDITIS-ELEGANS GENOME; PASSENGER-STRAND CLEAVAGE; C-ELEGANS; ENDOGENOUS SIRNAS; RNA INTERFERENCE; CHROMOSOME SEGREGATION; MOUSE OOCYTES; DROSOPHILA; EXPRESSION; REVEALS AB Endogenous small interfering RNAs (siRNAs) are a class of naturally occuring regulatory RNAs found in fungi, plants, and animals. Some endogenous siRNAs are required to silence transposons or function in chromosome segregation; however, the specific roles of most endogenous siRNAs are unclear. The helicase gene eri-6/7 was identified in the nematode Caenorhabditis elegans by the enhanced response to exogenous double-stranded RNAs (dsRNAs) of the null mutant. eri-6/7 encodes a helicase homologous to small RNA factors Armitage in Drosophila, SDE3 in Arabidopsis, and Mov10 in humans. Here we show that eri-6/7 mutations cause the loss of 26-nucleotide (nt) endogenous siRNAs derived from genes and pseudogenes in oocytes and embryos, as well as deficiencies in somatic 22-nucleotide secondary siRNAs corresponding to the same loci. About 80 genes are eri-6/7 targets that generate the embryonic endogenous siRNAs that silence the corresponding mRNAs. These 80 genes share extensive nucleotide sequence homology and are poorly conserved, suggesting a role for these endogenous siRNAs in silencing of and thereby directing the fate of recently acquired, duplicated genes. Unlike most endogenous siRNAs in C. elegans, eri-6/7-dependent siRNAs require Dicer. We identify that the eri-6/7-dependent siRNAs have a passenger strand that is similar to 19 nt and is inset by similar to 3-4 nts from both ends of the 26 nt guide siRNA, suggesting non-canonical Dicer processing. Mutations in the Argonaute ERGO-1, which associates with eri-6/7-dependent 26 nt siRNAs, cause passenger strand stabilization, indicating that ERGO-1 is required to separate the siRNA duplex, presumably through endonucleolytic cleavage of the passenger strand. Thus, like several other siRNA-associated Argonautes with a conserved RNaseH motif, ERGO-1 appears to be required for siRNA maturation. C1 [Fischer, Sylvia E. J.; Montgomery, Taiowa A.; Zhang, Chi; Breen, Peter C.; Hwang, Alexia; Ruvkun, Gary] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol,Dept Genet, Boston, MA 02115 USA. [Fahlgren, Noah; Sullivan, Christopher M.; Carrington, James C.] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA. RP Fischer, SEJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol,Dept Genet, Boston, MA 02115 USA. EM ruvkun@molbio.mgh.harvard.edu RI Carrington, James/A-4656-2012; Fahlgren, Noah/D-4404-2011; OI Carrington, James/0000-0003-3572-129X; Fahlgren, Noah/0000-0002-5597-4537; Montgomery, Taiowa/0000-0001-7857-3253 FU National Institutes of Health [GM44619]; Massachusetts General Hospital Executive Committee; Damon Runyon Cancer Research Foundation [DRG-2029-09] FX This work was supported by National Institutes of Health Grant GM44619 (to GR) and Massachusetts General Hospital Executive Committee of Research Fund for Medical Discovery fellowship awards (to CZ and SEJF). TAM is supported by Damon Runyon Cancer Research Foundation Grant DRG-2029-09. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 28 Z9 31 U1 0 U2 4 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 NOV PY 2011 VL 7 IS 11 AR e1002369 DI 10.1371/journal.pgen.1002369 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 851JM UT WOS:000297264500023 PM 22102828 ER PT J AU Lal, A Thomas, MP Altschuler, G Navarro, F O'Day, E Li, XL Concepcion, C Han, YC Thiery, J Rajani, DK Deutsch, A Hofmann, O Ventura, A Hide, W Lieberman, J AF Lal, Ashish Thomas, Marshall P. Altschuler, Gabriel Navarro, Francisco O'Day, Elizabeth Li, Xiao Ling Concepcion, Carla Han, Yoon-Chi Thiery, Jerome Rajani, Danielle K. Deutsch, Aaron Hofmann, Oliver Ventura, Andrea Hide, Winston Lieberman, Judy TI Capture of MicroRNA-Bound mRNAs Identifies the Tumor Suppressor miR-34a as a Regulator of Growth Factor Signaling SO PLOS GENETICS LA English DT Article ID DOWN-REGULATION; CELL-CYCLE; HEPATOCELLULAR-CARCINOMA; TARGET RECOGNITION; CANCER; GENES; EXPRESSION; APOPTOSIS; PROTEIN; P53 AB A simple biochemical method to isolate mRNAs pulled down with a transfected, biotinylated microRNA was used to identify direct target genes of miR-34a, a tumor suppressor gene. The method reidentified most of the known miR-34a regulated genes expressed in K562 and HCT116 cancer cell lines. Transcripts for 982 genes were enriched in the pull-down with miR-34a in both cell lines. Despite this large number, validation experiments suggested that similar to 90% of the genes identified in both cell lines can be directly regulated by miR-34a. Thus miR-34a is capable of regulating hundreds of genes. The transcripts pulled down with miR-34a were highly enriched for their roles in growth factor signaling and cell cycle progression. These genes form a dense network of interacting gene products that regulate multiple signal transduction pathways that orchestrate the proliferative response to external growth stimuli. Multiple candidate miR-34a-regulated genes participate in RAS-RAF-MAPK signaling. Ectopic miR-34a expression reduced basal ERK and AKT phosphorylation and enhanced sensitivity to serum growth factor withdrawal, while cells genetically deficient in miR-34a were less sensitive. Fourteen new direct targets of miR-34a were experimentally validated, including genes that participate in growth factor signaling (ARAF and PIK3R2) as well as genes that regulate cell cycle progression at various phases of the cell cycle (cyclins D3 and G2, MCM2 and MCM5, PLK1 and SMAD4). Thus miR-34a tempers the proliferative and pro-survival effect of growth factor stimulation by interfering with growth factor signal transduction and downstream pathways required for cell division. C1 [Lal, Ashish; Thomas, Marshall P.; Navarro, Francisco; O'Day, Elizabeth; Thiery, Jerome; Rajani, Danielle K.; Deutsch, Aaron; Lieberman, Judy] Childrens Hosp Boston, Program Cellular & Mol Med, Immune Dis Inst, Boston, MA 02115 USA. [Lal, Ashish; Thomas, Marshall P.; Navarro, Francisco; O'Day, Elizabeth; Thiery, Jerome; Rajani, Danielle K.; Deutsch, Aaron; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Lal, Ashish; Li, Xiao Ling] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Altschuler, Gabriel; Hofmann, Oliver; Hide, Winston] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Concepcion, Carla; Han, Yoon-Chi; Ventura, Andrea] Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, New York, NY 10021 USA. RP Lal, A (reprint author), Childrens Hosp Boston, Program Cellular & Mol Med, Immune Dis Inst, Boston, MA 02115 USA. EM lalas@mail.nih.gov; lieberman@idi.harvard.edu RI Hofmann, Oliver/F-1800-2013; Hide, Winston Hide/C-7217-2009; Lieberman, Judy/A-2717-2015; OI Hofmann, Oliver/0000-0002-7738-1513; Hide, Winston Hide/0000-0002-8621-3271; Deutsch, Aaron/0000-0001-6750-5335; Ventura, Andrea/0000-0003-4320-9907 FU GSK-IDI Alliance; NSF FX This work was supported by a research grant (JL) and fellowship (FN) from the GSK-IDI Alliance and by NSF predoctoral fellowships (MPT, DKR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 91 Z9 92 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD NOV PY 2011 VL 7 IS 11 AR e1002363 DI 10.1371/journal.pgen.1002363 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 851JM UT WOS:000297264500018 PM 22102825 ER PT J AU Huang, AJ Kattapuram, SV AF Huang, Ambrose J. Kattapuram, Susan V. TI Musculoskeletal Neoplasms: Biopsy and Intervention SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Biopsy; Intervention; Tumor; Infection; Spondylodiscitis; Sarcoma; Metastasis ID PERCUTANEOUS RADIOFREQUENCY ABLATION; CORE-NEEDLE-BIOPSY; EXTREMITY COMPARTMENTAL ANATOMY; METASTASES INVOLVING BONE; CT-GUIDED BIOPSY; OSTEOID OSTEOMA; INTRALESIONAL INJECTION; ETHIBLOC INJECTION; CLINICAL-RELEVANCE; FOLLOW-UP AB Percutaneous core needle biopsy and fine-needle aspiration are safe and cost-effective methods and can be important steps in the workup of a bone or soft tissue lesion. These procedures should be performed in collaboration with the orthopedic oncologist who performs the definitive surgery. In the extremities, attention to compartmental anatomy is paramount. With frozen section evaluation at the time of biopsy, the chances of a nondiagnostic specimen necessitating rebiopsy are minimized. The principles underlying the percutaneous approach to various lesions are valuable and can be applied to minimally invasive percutaneous therapy for bone and soft tissue lesions. C1 [Huang, Ambrose J.; Kattapuram, Susan V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kattapuram, SV (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. EM skattapuram@partners.org NR 52 TC 17 Z9 20 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD NOV PY 2011 VL 49 IS 6 BP 1287 EP + DI 10.1016/j.rcl.2011.07.010 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 853OT UT WOS:000297436300012 PM 22024299 ER PT J AU Wen, LS Noble, JA AF Wen, Leana S. Noble, Jeanne A. TI A Case of a Young Girl With Fever and Seizure SO ACADEMIC EMERGENCY MEDICINE LA English DT Editorial Material ID PULMONARY TUBERCULOSIS; EMERGENCY; CHILDREN C1 [Wen, Leana S.] Massachusetts Gen Hosp, Div Emergency Med, Brigham & Womens Hosp, Boston, MA 02114 USA. [Noble, Jeanne A.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. RP Wen, LS (reprint author), Massachusetts Gen Hosp, Div Emergency Med, Brigham & Womens Hosp, Boston, MA 02114 USA. EM wen.leana@gmail.com OI Wen, Leana/0000-0003-0259-0537 NR 13 TC 1 Z9 1 U1 0 U2 2 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 NOV PY 2011 VL 18 IS 11 BP e86 EP e92 DI 10.1111/j.1553-2712.2011.01193.x PG 7 WC Emergency Medicine SC Emergency Medicine GA 849EG UT WOS:000297107800001 PM 22092908 ER PT J AU Kontos, N Querques, J Freudenreich, O AF Kontos, Nicholas Querques, John Freudenreich, Oliver TI Two's Company, Three Hundred Million's a Crowd: Balancing Clinical Integrity and Population Consciousness in Medical Education SO ACADEMIC MEDICINE LA English DT Editorial Material C1 [Kontos, Nicholas; Querques, John] Massachusetts Gen Hosp, Psychosomat Med Consultat Psychiat Fellowship Pro, Boston, MA 02114 USA. [Kontos, Nicholas; Querques, John; Freudenreich, Oliver] Harvard Univ, Sch Med, Boston, MA USA. [Freudenreich, Oliver] Massachusetts Gen Hosp, Episode & Early Psychosis Program 1, Boston, MA 02114 USA. RP Kontos, N (reprint author), Massachusetts Gen Hosp, Psychosomat Med Consultat Psychiat Fellowship Pro, 55 Fruit St,Warren 605, Boston, MA 02114 USA. EM nkontos@partners.org RI liu, jing/D-9482-2012 NR 3 TC 3 Z9 3 U1 0 U2 3 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 NOV PY 2011 VL 86 IS 11 BP 1341 EP 1341 DI 10.1097/ACM.0b013e3182308cea PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 842UB UT WOS:000296624900030 PM 22030640 ER PT J AU Melloni, C James, SK White, JA Giugliano, RP Harrington, RA Huber, K Tricoci, P Armstrong, PW Van de Werf, F Montalescot, G Califf, RM Newby, LK AF Melloni, Chiara James, Stefan K. White, Jennifer A. Giugliano, Robert P. Harrington, Robert A. Huber, Kurt Tricoci, Pierluigi Armstrong, Paul W. Van de Werf, Frans Montalescot, Gilles Califf, Robert M. Newby, L. Kristin CA EARLY ACS Investigators TI Safety and efficacy of adjusted-dose eptifibatide in patients with acute coronary syndromes and reduced renal function SO AMERICAN HEART JOURNAL LA English DT Article ID GLYCOPROTEIN IIB/IIIA INHIBITORS; RAPID RISK STRATIFICATION; SUPPRESS ADVERSE OUTCOMES; PLACEBO-CONTROLLED TRIAL; UNSTABLE ANGINA; MYOCARDIAL-INFARCTION; EARLY IMPLEMENTATION; INTERVENTION; PHARMACOKINETICS; PHARMACODYNAMICS AB Background Dose adjustment of renally excreted antithrombotic drugs is recommended for patients with reduced renal function. We examined the influence of dose modification on bleeding and efficacy. Methods Based on initial study drug infusion rate, Early GP IIb/IIIa Inhibition in non-ST-segment elevation acute coronary syndromes (EARLY ACS) patients were categorized into groups: standard dose (2 mu g/kg/min; estimated creatinine clearance [eCrCl] >= 50 ml/min), adjusted dose (1 mu g/kg/min; eCrCl <50 ml/min, per protocol), excess dose (2 mu g/kg/min; eCrCl <50 ml/min). We explored relationships among initial dosing, randomized treatment assignment, and bleeding and ischemic end points (96-h composite of death, myocardial infarction [MI], recurrent ischemia requiring urgent revascularization or thrombotic bailout, and 30-d death or MI). Results Of 8,708 patients with eCrCl and dosing data, 19% had eCrCl <50 ml/min. Of these, 13% received adjusted dose eptifibatide and 6% received an excess dose. Across all dosing groups, no significant reductions were found in ischemic end points between early versus delayed provisional eptifibatide (OR 1.14, 95% CI 0.80-1.65; OR 1.13, 95% CI 0.81-1.56, respectively, for 96-h and 30-d composite end points). Bleeding risk was not significantly increased in the early versus delayed provisional treatment group in either the adjusted (OR 1.50, 95% CI 0.95-2.39) or excess dose group (OR 1.67, 95% CI 0.85-3.39). There were no significant interactions between dose group and treatment strategy on bleeding or efficacy. Conclusion Similar to observations in practice, despite guidelines recommendations and protocol guidance, 34% of EARLY ACS patients with reduced renal function failed to receive an appropriately adjusted study drug infusion. Use of an appropriately adjusted eptifibatide infusion was not associated with expected reductions in bleeding among patients with renal insufficiency. (Am Heart J 2011;162:884-892.e1.) C1 [Melloni, Chiara; White, Jennifer A.; Harrington, Robert A.; Tricoci, Pierluigi; Newby, L. Kristin] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. [Melloni, Chiara; White, Jennifer A.; Harrington, Robert A.; Tricoci, Pierluigi; Newby, L. Kristin] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27705 USA. [James, Stefan K.] Uppsala Univ, Uppsala Clin Res Ctr, Dept Med Sci, Uppsala, Sweden. [Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Huber, Kurt] Wilhelminenspital Stadt Wien, Dept Med, Vienna, Austria. [Armstrong, Paul W.] Univ Alberta, Edmonton, AB, Canada. [Van de Werf, Frans] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. [Van de Werf, Frans] Leuven Coordinating Ctr, Louvain, Belgium. [Montalescot, Gilles] Hop La Pitie Salpetriere, Inst Cardiol, Paris, France. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC USA. RP Melloni, C (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27705 USA. EM mello004@mc.duke.edu OI Van de Werf, Frans/0000-0001-9479-7767 FU AstraZeneca; Sanofi-Aventis; BMS; Eli Lilly; Schering-Plough; Merck; Bristol-Myers Squibb; Medtronic; Bayer; Boehringer-Ingelheim; Daiichi Sankyo; Fibrex; Portola; Medicines Company; Boston Scientific; Cordis/Johnson Johnson; GlaxoSmithKline; Pfizer; Schering-Plough Research Institute; Portola Pharmaceutical; Roche; Merck through the Duke Clinical Research Institute FX Stefan K. James: Research grants and speaker fees received from AstraZeneca, Sanofi-Aventis, BMS, Eli Lilly, and Schering-Plough.; Robert A. Harrington: Research funding and consulting with Schering-Plough, now Merck. A complete listing of Dr. Harrington's relationships with industry is available at http://www.dcri.duke.edu/research/coi.jsp.; Kurt Huber: Research grants from Bristol-Myers Squibb, Eli Lilly, Medtronic, Sanofi-Aventis; consulting fees from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Fibrex, Eli Lilly, Portola, Sanofi-Aventis, Schering-Plough, and The Medicines Company; lecture fees from AstraZeneca, Boehringer-Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cordis/Johnson & Johnson, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Pfizer, and Sanofi-Aventis.; Paul W. Armstrong: Research grant or contract from Schering-Plough Research Institute, Portola Pharmaceutical, AstraZeneca, and Merck, which partially supports his university salary and/or research projects. A complete listing of Dr. Armstrong's relationships with industry is available at http://www.vigour.ualberta.ca.; Frans Van de Werf: Research grants from Schering-Plough (now Merck) and Roche; advisory board and speakers fee from Schering- Plough, Merck, and Roche.; L. Kristin Newby: Research grant from Schering-Plough and Merck through the Duke Clinical Research Institute; consulting honoraria from Schering-Plough. A complete listing of Dr. Newby's relationships with industry is available at www.dcri.duke.edu/research/coi.jsp. NR 27 TC 2 Z9 3 U1 1 U2 8 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 NOV PY 2011 VL 162 IS 5 DI 10.1016/j.ahj.2011.08.020 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 851DE UT WOS:000297247800014 PM 22093205 ER PT J AU Peacock, WF Nagurney, J Birkhahn, R Singer, A Shapiro, N Hollander, J Glynn, T Nowak, R Safdar, B Miller, C Peberdy, M Counselman, F Chandra, A Kosowsky, J Neuenschwander, J Schrock, J Plantholt, S Lewandrowski, E Wong, V Kupfer, K Diercks, D AF Peacock, W. Frank Nagurney, John Birkhahn, Robert Singer, Adam Shapiro, Nathan Hollander, Judd Glynn, Ted Nowak, Richard Safdar, Basmah Miller, Chadwick Peberdy, Mary Counselman, Francis Chandra, Abhinav Kosowsky, Joshua Neuenschwander, James Schrock, Jon Plantholt, Stephen Lewandrowski, Elizabeth Wong, Vance Kupfer, Ken Diercks, Deborah TI Myeloperoxidase in the diagnosis of acute coronary syndromes: The importance of spectrum SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; UNSTABLE ANGINA-PECTORIS; CHEST-PAIN; EMERGENCY-DEPARTMENT; NEUTROPHIL; PHYSICIANS; OXIDATION; RISK AB Background Myeloperoxidase (MPO) is proposed for risk stratification in patients with suspected acute coronary syndromes (ACSs). We determined if MPO has diagnostic value in patients being evaluated for ACS. Method MIDAS was an 18-center prospective study enrolling suspected ACS emergency department patients who presented <8 hours after symptom onset and in whom serial cardiac markers and objective cardiac perfusion testing were planned. Blinded MPO (Biosite, Inc, San Diego, CA) and troponin I (Triage Cardio 3; Biosite, Inc) were drawn at arrival, and Troponin I (TnI) was measured at 90, 180, and 360 minutes. Final diagnoses were adjudicated by the local investigator blinded to study assay. Results Of 1,018 patients, 54% were male, 26% black, with a mean age of 58 +/- 13 years. Diagnoses were ACS in 288 (23%) and noncardiac chest pain (NCCP) in 788 (77%). Of patients with ACS, 94 (9.2%) had a myocardial infarction (MI) at presentation (69 non-ST-elevation MI, 25 ST-elevation MI), and 136 had unstable angina. Using a cutpoint of 210 ng/mL to provide 90% specificity, MPO had a sensitivity of 0.18; negative predictive value, 0.69; positive predictive value, 0.47; negative likelihood ratio, 0.91; and a positive likelihood ratio of 1.83 to differentiate ACS and NCCP. Because of the large overlap of quartiles, MPO was not clinically useful to predict serial TnI changes. The C statistics +/- 95% CI for MPO differentiating ACS from NCCP and for AMI versus NCCP were 0.629 +/- 0.04 and 0.666 +/- 0.06, respectively. Conclusions Myeloperoxidase has insufficient accuracy for decision making in patients with suspected ACS. (Am Heart J 2011;162:893-9.) C1 [Peacock, W. Frank] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Nagurney, John; Lewandrowski, Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Birkhahn, Robert] New York Methodist Hosp, Brooklyn, NY USA. [Singer, Adam] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Shapiro, Nathan] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Hollander, Judd] Univ Penn, Philadelphia, PA 19104 USA. [Glynn, Ted] Ingham Reg Med Ctr, Lansing, MI USA. [Nowak, Richard] Henry Ford Hlth Syst, Detroit, MI USA. [Safdar, Basmah] Yale Univ, New Haven, CT USA. [Miller, Chadwick] Wake Forrest Baptist Hosp, Winston Salem, NC USA. [Peberdy, Mary] Virginia Commonwealth Univ, Richmond, VA USA. [Counselman, Francis] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Chandra, Abhinav] Duke Univ, Durham, NC USA. [Kosowsky, Joshua] Brigham & Womens Hosp, Boston, MA 02115 USA. [Neuenschwander, James] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Schrock, Jon] Metrohlth Med Ctr, Cleveland, OH USA. [Plantholt, Stephen] St Agnes Hosp, Baltimore, MD USA. [Wong, Vance; Kupfer, Ken] Alere Inc, San Diego, CA USA. [Diercks, Deborah] Univ Calif, Sacramento, CA USA. RP Peacock, WF (reprint author), Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM meltonc@ccf.org RI Shapiro, Nathan/F-1718-2016; OI Hollander, Judd/0000-0002-1318-2785 NR 27 TC 15 Z9 16 U1 0 U2 6 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 NOV PY 2011 VL 162 IS 5 DI 10.1016/j.ahj.2011.08.017 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 851DE UT WOS:000297247800015 PM 22093206 ER PT J AU Scirica, BM Bhatt, DL Braunwald, E Steg, PG Davidson, J Hirshberg, B Ohman, P Price, DL Chen, R Udell, J Raz, I AF Scirica, Benjamin M. Bhatt, Deepak L. Braunwald, Eugene Steg, Ph. Gabriel Davidson, Jaime Hirshberg, Boaz Ohman, Peter Price, Deborah L. Chen, Roland Udell, Jacob Raz, Itamar CA SAVOR-TIMI53 Steering Comm Investi TI The design and rationale of the Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus-Thrombolysis in Myocardial Infarction (SAVOR-TIMI) 53 Study SO AMERICAN HEART JOURNAL LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; IMPROVES GLYCEMIC CONTROL; BLOOD-GLUCOSE CONTROL; CARDIOVASCULAR OUTCOMES; SECONDARY PREVENTION; THERAPY; METFORMIN; DISEASE; ASPIRIN; PIOGLITAZONE AB Objectives Saxagliptin, a dipeptidyl peptidase 4 inhibitor, improves glycemic control in patients with type 2 diabetes mellitus (T2DM) by increasing endogenous active, intact glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide in response to food, which augments insulin secretion and decreases glucagon release. Research Design and Methods SAVOR-TIMI 53 is a phase 4, randomized, double-blind, placebo-controlled trial conducted in 25 countries that is designed to evaluate the safety and efficacy of saxagliptin during long-term treatment of approximately 16,500 patients with T2DM. Eligible patients who are either treatment naive or on any background antidiabetic treatment (except incretin therapy) with history of established cardiovascular (CV) disease or multiple risk factors are randomized 1: 1 to saxagliptin 5 mg QD (2.5 mg in subjects with moderate/severe renal impairment) or matching placebo, stratified by qualifying disease state. The primary end point is the composite of CV death, nonfatal myocardial infarction, or nonfatal ischemic stroke. The trial will continue until approximately 1,040 primary end points accrue, providing 85% power to identify a 17% relative reduction of the primary end point with saxagliptin versus placebo and 98% power to test for noninferiority of saxagliptin versus placebo (reject the upper limit of 95% CI for a hazard ratio <1.3 at a 1-sided alpha of .025). Conclusion SAVOR-TIMI 53 is testing the hypothesis that treatment with saxagliptin is safe and reduces CV events in high-risk patients with T2DM. (Am Heart J 2011;162:818-825.e6.) C1 [Scirica, Benjamin M.; Bhatt, Deepak L.; Braunwald, Eugene; Udell, Jacob] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. [Scirica, Benjamin M.; Bhatt, Deepak L.; Braunwald, Eugene; Udell, Jacob] Harvard Univ, Sch Med, Boston, MA USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Steg, Ph. Gabriel] Univ Paris 07, INSERM, U698, Paris, France. [Steg, Ph. Gabriel] Hop Bichat Claude Bernard, AP HP, F-75877 Paris, France. [Davidson, Jaime] Univ Texas SW Med Ctr Dallas, Div Endocrinol, Dept Internal Med, Dallas, TX 75390 USA. [Hirshberg, Boaz; Ohman, Peter; Price, Deborah L.] AstraZeneca Res & Dev, Wilmington, DE USA. [Chen, Roland] Bristol Myers Squibb Co, Princeton, NJ USA. [Raz, Itamar] Hadassah Univ Hosp, Dept Med, Diabet Unit, IL-91240 Jerusalem, Israel. RP Scirica, BM (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM bscirica@partners.org FU AstraZeneca; Bristol-Myers Squibb; Merck; Johnson Johnson; Bayer Healthcare; Gilead Sciences; Lexicon; Arena Pharmaceuticals; Eisai; Sanofi Aventis; Medicines Company FX Dr Scirica reports research grants from AstraZeneca, Bristol-Myers Squibb, Merck, Johnson & Johnson, Bayer Healthcare, and Gilead Sciences and consultancy fees from Gilead Sciences, Lexicon, and Arena Pharmaceuticals. Dr Bhatt reports research grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Sanofi Aventis, and The Medicines Company. Dr Braunwald reports research grants from AstraZeneca and Bristol-Myers Squibb. Dr Steg reports research grants from Servier. Dr Davidson reports serving on advisory panels for AstraZeneca, Bristol-Myers Squibb, Merck, Johnson & Johnson, Boehringer Ingelheim, Eli Lilly, Generex Biotechnology, Novo Nordisk A/S, Roche Diagnostics, and Takeda Pharmaceutical Company and on the speaker's bureau of Eli Lilly and Takeda Pharmaceutical Company. Drs Hirshberg and Ohman and Ms Price are employees of and hold stock in AstraZeneca. Dr Chen is an employee of and holds stock in Bristol-Myers Squibb. Dr Udell reports no conflicts. Dr Raz has received honoraria/expenses for advisory board participation from AstraZeneca, Bristol-Myers Squibb, Novo Nordisk, Merck Sharp & Dohme, and Eli Lilly; served as a consultant for Andromeda, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, HealOr, Insuline, Teva, and TransPharma; and participated in speakers bureaus for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Novo Nordisk, Johnson & Johnson, and Roche. The authors are solely responsible for the design and conduct of this study, all study analyses, and the drafting and editing of the manuscript and its final contents. NR 32 TC 50 Z9 54 U1 1 U2 13 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 NOV PY 2011 VL 162 IS 5 DI 10.1016/j.ahj.2011.08.006 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 851DE UT WOS:000297247800005 PM 22093196 ER PT J AU Soleimani, M Khazalpour, M Cheng, GM Zhang, ZH Acevedo-Bolton, G Saloner, DA Mishra, R Wallace, AW Guccione, JM Ge, L Ratcliffe, MB AF Soleimani, Mehrdad Khazalpour, Michael Cheng, Guangming Zhang, Zhihong Acevedo-Bolton, Gabriel Saloner, David A. Mishra, Rakesh Wallace, Arthur W. Guccione, Julius M. Ge, Liang Ratcliffe, Mark B. TI Moderate Mitral Regurgitation Accelerates Left Ventricular Remodeling After Posterolateral Myocardial Infarction SO ANNALS OF THORACIC SURGERY LA English DT Article ID MAGNETIC-RESONANCE; 3-DIMENSIONAL ECHOCARDIOGRAPHY; REPAIR; REVASCULARIZATION; QUANTIFICATION; METAANALYSIS; SEVERITY; MYOCYTES; VOLUMES; STRESS AB Background. Chronic ischemic mitral regurgitation (MR) is associated with poor outcome. However, the effect of chronic ischemic MR on left ventricular (LV) remodeling after posterolateral myocardial infarction (MI) remains controversial. We tested the hypothesis that moderate MR accelerates LV remodeling after posterolateral MI. Methods. Posterolateral MI was created in 10 sheep. Cardiac magnetic resonance imaging was performed 2 weeks before and 2, 8, and 16 weeks after MI. Left ventricular and right ventricular volumes were measured, and regurgitant volume was calculated as the difference between LV and right ventricle stroke volumes. Results. Multivariate mixed effects regression showed that LV volumes at end diastole and end systole and LV sphericity were strongly correlated with both regurgitant volume (p < 0.0001, p = 0.0086, and p = 0.0007, respectively) and percent infarct area (p = 0.0156, p = 0.0307, and p < 0.0001, respectively). Conversely, whereas LV hypertrophy (LV wall volume) increased from 2 weeks to 16 weeks after MI, there was no effect of either regurgitant volume or percent infarct. Conclusions. Moderate MR accelerates LV remodeling after posterolateral MI. Further studies are needed to determine whether mitral valve repair is able to slow or reverse MI remodeling after posterolateral MI. (Ann Thorac Surg 2011;92:1614-20) (C) 2011 by The Society of Thoracic Surgeons C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Ratcliffe, MB (reprint author), San Francisco VA Med Ctr, Div Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA. EM mark.ratcliffe@va.gov FU National Institutes of Health [R01-HL-084431, R01-HL-077921] FX This study was supported by National Institutes of Health grants R01-HL-084431 (Dr Ratcliffe) and R01-HL-077921 (Dr Guccione). NR 33 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2011 VL 92 IS 5 BP 1614 EP 1620 DI 10.1016/j.athoracsur.2011.05.117 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 846TF UT WOS:000296925400020 PM 21945222 ER PT J AU Shah, DK Li, Z Park, SJ Daly, RC Dearani, JA Schaff, HV Sundt, TM AF Shah, Dipesh K. Li, Zhuo Park, Soon J. Daly, Richard C. Dearani, Joseph A. Schaff, Hartzell V. Sundt, Thoralf M., III TI Replacement of the Infected Composite Aortic Root Prosthesis SO ANNALS OF THORACIC SURGERY LA English DT Article ID VALVE ENDOCARDITIS; ASCENDING AORTA; EXPERIENCE; REOPERATIONS; ALLOGRAFT; SURGERY; RISK AB Background. We sought to evaluate freedom from reinfection after surgery for infected aortic root replacement (ARR) and the impact of use of synthetic material at reoperation. Methods. Adult patients (aged more than 18 years) undergoing surgery for infected composite aortic root prosthesis at our institution were identified and their perioperative outcomes and late survival evaluated. Results. Between January 1, 1993, and December 31, 2009, 15 patients (male, 87%; mean [SD] age, 57 [16] years) underwent surgery. All but 1 patient (6.7%) underwent reconstruction with a homograft. Eight patients (53.3%) required synthetic material to complete the repair, including 4 patients who underwent hemiarch reconstruction. Ten patients (66.7%) had circulatory arrest (mean [SD] time, 23.3 [11.0] minutes) and 3 (20.0%) underwent concomitant coronary artery bypass grafting. The 30-day mortality rate was 13.3% (n = 2). Three patients (20.0%)-2 of whom had positive blood cultures in hospital after redo ARR-had reinfection, for which 2 underwent re-replacement of the aortic root. Survival was 86.7%, 65.0%, and 50.6%, and freedom from reinfection was 90.9%, 79.5%, and 79.5% at 3, 6, and 12 months, respectively. Freedom from reinfection was less for the patients who had positive blood cultures within 2 weeks of redo ARR (p < 0.03) and for patients who had multiple previous sternotomies (p = 0.006). Use of synthetic graft material had no adverse impact. Conclusions. Infected ARR prostheses can be replaced with a homograft with favorable outcomes. Use of synthetic material to complete the repair does not adversely impact outcome. (Ann Thorac Surg 2011; 92: 1651-6) (C) 2011 by The Society of Thoracic Surgeons C1 [Sundt, Thoralf M., III] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Mayo Clin, Div Cardiovasc Surg, Rochester, MN USA. Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA. RP Sundt, TM (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St, Boston, MA 02114 USA. EM tsundt@partners.org OI Schaff, Hartzell/0000-0003-0994-027X NR 16 TC 3 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2011 VL 92 IS 5 BP 1651 EP 1656 DI 10.1016/j.athoracsur.2011.05.115 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 846TF UT WOS:000296925400028 PM 21937018 ER PT J AU Kim, S Ott, HC Wright, CD Wain, JC Morse, C Gaissert, HA Donahue, DM Mathisen, DJ Lanuti, M AF Kim, Samuel Ott, Harald C. Wright, Cameron D. Wain, John C. Morse, Christopher Gaissert, Henning A. Donahue, Dean M. Mathisen, Douglas J. Lanuti, Michael TI Pulmonary Resection of Metastatic Sarcoma: Prognostic Factors Associated With Improved Outcomes SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 31-FEB 02, 2011 CL San Diego, CA SP Soc Thorac Surg ID SOFT-TISSUE SARCOMA; SURVIVAL; METASTASECTOMY; MANAGEMENT; NUMBER AB Background. There are few data to predict the benefit of pulmonary metastasectomy in patients with extrathoracic sarcoma. This study analyzes prognostic factors associated with improved outcomes. Methods. Between June 2002 and December 2008, 97 patients underwent pulmonary resection for metastatic sarcoma at Massachusetts General Hospital. Eight patients were excluded because of lack of follow-up data. Analysis was performed using Kaplan-Meier estimates of survival, log-rank test, and multivariate Cox model. Results. Overall 5-year survival for the cohort was 50.1%. Patients who had multiple operations for recurrent pulmonary metastases had better 5-year survival compared with patients who had a single operation (69 versus 41%; p = 0.017). Median disease-free survival (DFS) for the reoperation group was 12.9 months compared with 9.1 months for the single-operation group (p < 0.028). Patients with a disease-free interval (DFI) greater than 12 months from detection of primary sarcoma to pulmonary metastasectomy had improved survival compared with those whose DFI was less than 12 months (p < 0.0001). Patients with bilateral metastasectomy had lower 5-year survival compared with metastasectomy for unilateral disease (22% versus 68%; p < 0.0001). Two or more metastases were associated with poorer outcome compared with a single metastasis (p = 0.0007). A positive resection margin portended worse survival compared with a negative resection margin (p = 0.004). Patients with lesions larger than 3 cm had decreased survival compared with patients with lesions smaller than 3 cm (p = 0.017) with no difference in median DFS. Histologic type, grade of tumor, and use of chemotherapy had no effect on survival. Multivariate analysis showed that patients with a DFI greater than 12 months (p = 0.001), single-sided metastasis (p = 0.001), negative margins (p = 0.002), and multiple operations (p = 0.018) had better survival. Conclusions. Pulmonary metastasectomy for sarcoma can be associated with prolonged survival. Tumor resectability, DFI, number of metastases, and laterality are important factors in determining patient selection for curative surgical intervention. Repeated pulmonary metastasectomy in select patients may improve survival despite recurrent disease. (Ann Thorac Surg 2011; 92: 1780-7) (C) 2011 by The Society of Thoracic Surgeons C1 [Kim, Samuel; Ott, Harald C.; Wright, Cameron D.; Wain, John C.; Morse, Christopher; Gaissert, Henning A.; Donahue, Dean M.; Mathisen, Douglas J.; Lanuti, Michael] Harvard Univ, Div Thorac Surg, Sch Med, Massachusetts Gen Hosp, Boston, MA 01478 USA. RP Lanuti, M (reprint author), Harvard Univ, Div Thorac Surg, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,Blake 1570, Boston, MA 01478 USA. EM mlanuti@partners.org NR 21 TC 36 Z9 39 U1 0 U2 1 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 NOV PY 2011 VL 92 IS 5 BP 1780 EP 1786 DI 10.1016/j.athoracsur.2011.05.081 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 846TF UT WOS:000296925400050 PM 22051274 ER PT J AU Raz, DJ Lanuti, M Gaissert, HC Wright, CD Mathisen, DJ Wain, JC AF Raz, Dan J. Lanuti, Michael Gaissert, Henning C. Wright, Cameron D. Mathisen, Douglas J. Wain, John C. TI Outcomes of Patients With Isolated Adrenal Metastasis From Non-Small Cell Lung Carcinoma SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 31-FEB 02, 2011 CL San Diego, CA SP Soc Thorac Surg ID LAPAROSCOPIC ADRENALECTOMY; CANCER AB Background. Long-term survival of patients who undergo surgical resection of isolated adrenal metastasis from non-small cell lung cancer (NSCLC) has been reported. The aim of this study was to compare survival of patients who underwent adrenalectomy with those treated nonoperatively, and to analyze clinical characteristics associated with long-term survival. Methods. Between January 1994 and July 2010, 37 patients with isolated adrenal metastasis from NSCLC were identified. Twenty patients underwent adrenalectomy. Patients did not undergo adrenalectomy owing to suspicion of N2 disease, medical comorbidities, or patient preference. Seven patients (35%) treated surgically had tumors that were ipsilateral to their primary tumor, and 8 (40%) had metachronous metastases. Results. Five-year overall survival was 34% for patients treated operatively and 0% for patients treated nonoperatively (p = 0.002). Among patients treated with adrenalectomy, patients with ipsilateral metastases had a 5-year survival of 83% compared with 0% for patients with contralateral metastases (p = 0.003). Patients without mediastinal nodal disease had a 5-year survival of 52% compared with 0% for patients with mediastinal nodal disease (p = 0.008). Survival of patients who underwent adrenalectomy for synchronous and metachronous adrenal metastases was not significantly different (p = 0.81). Conclusions. Surgical resection of isolated adrenal metastasis from lung cancer provides a survival benefit in well-selected patients compared with nonoperative management. No patient with contralateral adrenal metastases or mediastinal nodal disease survived long term after adrenalectomy. The time interval between treatment of the primary lung cancer and adrenal metastasis was not significantly associated with survival, but the cohort size was small. (Ann Thorac Surg 2011; 92: 1788 -93) (C) 2011 by The Society of Thoracic Surgeons C1 [Raz, Dan J.; Lanuti, Michael; Gaissert, Henning C.; Wright, Cameron D.; Mathisen, Douglas J.; Wain, John C.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Raz, DJ (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM draz@partners.org NR 10 TC 27 Z9 30 U1 0 U2 3 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 NOV PY 2011 VL 92 IS 5 BP 1788 EP 1792 DI 10.1016/j.athoracsur.2011.05.116 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 846TF UT WOS:000296925400052 PM 21944257 ER PT J AU Rajbanshi, BG Rodrigues, E Lynch, JJ Gulati, R Sundt, TM AF Rajbanshi, Bijoy G. Rodrigues, Eduardo Lynch, James J. Gulati, Rajiv Sundt, Thoralf M., III TI Coronary Artery Spasm After Cryo Maze III Procedure SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID ATRIAL-FIBRILLATION; CATHETER ABLATION AB The Cox Maze III procedure has been simplified with the availability of tissue ablation devices; however, complications related to their use are recognized. We report a case of 45-year-old woman who underwent mitral valve repair and concomitant Cryo-Maze procedure. She had reversible right coronary artery spasm develop after the procedure demonstrated by ST-segment elevation changes and coronary angiography, which was reversed with intracoronary nitroglycerin. The region of spasm suggested it as a consequence of proximity of the right coronary artery to the right atrial ablation lines. (Ann Thorac Surg 2011; 92: 1884-7) (C) 2011 by The Society of Thoracic Surgeons C1 [Sundt, Thoralf M., III] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02117 USA. Mayo Clin & Mayo Fdn, Div Cardiovasc Surg, Dept Anesthesiol, Rochester, MN USA. Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, Rochester, MN USA. RP Sundt, TM (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St,POB 652, Boston, MA 02117 USA. EM tsundt@partners.org NR 8 TC 1 Z9 3 U1 0 U2 1 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 NOV PY 2011 VL 92 IS 5 BP 1884 EP 1887 DI 10.1016/j.athoracsur.2011.04.113 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 846TF UT WOS:000296925400075 PM 22051287 ER PT J AU Chang, AY Piette, EW Foering, KP Tenhave, TR Okawa, J Werth, VP AF Chang, Aileen Y. Piette, Evan W. Foering, Kristen P. Tenhave, Thomas R. Okawa, Joyce Werth, Victoria P. TI Response to Antimalarial Agents in Cutaneous Lupus Erythematosus SO ARCHIVES OF DERMATOLOGY LA English DT Article ID SEVERITY INDEX; DISEASE AREA; QUINACRINE; RESISTANT; HYDROXYCHLOROQUINE; CHLOROQUINE; DERMATOLOGY; CLASSIFICATION; ASSOCIATION; THERAPY AB Objective: To demonstrate response to antimalarial agents in patients with cutaneous lupus erythematosus (CLE) using activity scores from the Cutaneous Lupus Erythematosus Disease Area and Severity Index, a validated outcome measure. Design: Prospective, longitudinal cohort study. Setting: University cutaneous autoimmune disease clinic. Participants: A total of 128 patients with CLE who presented from January 2007 to July 2010 and had at least 2 visits with activity scores. Intervention: Administration of antimalarial agents. Main Outcome Measures: Response was defined by a 4-point or 20% decrease in activity score. Response to initiation was determined by the difference between the scores before treatment and at the first visit at least 2 months after treatment. Response to continuation was determined by the difference between the scores at the first visit and the most recent visit while undergoing treatment. Results: Of 11 patients who initiated treatment with hydroxychloroquine, 55% were responders (n = 6), showing a decrease in median (interquartile range [IQR]) activity score from 8.0 (3.5-13.0) to 3.0 (1.8-7.3) (P = .03). Of 15 patients for whom hydroxychloroquine failed, 67% were responders to initiation of hydroxychloroquine-quinacrine therapy (n = 10), showing a decrease in median (IQR) activity score from 6.0 (4.8-8.3) to 3.0 (0.75-5.0) (P = .004). Nine of 21 patients who continued hydroxychloroquine treatment (43%), and 9 of 21 patients who continued hydroxychloroquine-quinacrine (43%) were responders, showing a decrease in median (IQR) activity score from 6.0 (1.5-9.5) to 1.0 (0.0-4.5) (P = .01) and 8.5 (4.25-17.5) to 5.0 (0.5-11.5) (P = .01), respectively. Conclusions: The use of quinacrine with hydroxychloroquine is associated with response in patients for whom hydroxychloroquine monotherapy fails. Further reduction in disease activity can be associated with continuation of treatment with antimalarial agents. C1 [Chang, Aileen Y.; Piette, Evan W.; Foering, Kristen P.; Okawa, Joyce; Werth, Victoria P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Chang, Aileen Y.; Piette, Evan W.; Foering, Kristen P.; Okawa, Joyce; Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Foering, Kristen P.] Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Tenhave, Thomas R.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Perelman Ctr Adv Med, Dept Dermatol, 3400 Civ Ctr Blvd,Ste 1-330A, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU National Institutes of Health [NIH K24-AR 18 02207]; Doris Duke Charitable Foundation FX This work was supported by National Institutes of Health grant NIH K24-AR 18 02207 (Dr Werth) and a grant from the Doris Duke Charitable Foundation to the Perelman School of Medicine at the University of Pennsylvania to fund Clinical Research Fellow Ms Chang. NR 30 TC 30 Z9 32 U1 0 U2 0 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 NOV PY 2011 VL 147 IS 11 BP 1261 EP 1267 DI 10.1001/archdermatol.2011.191 PG 7 WC Dermatology SC Dermatology GA 850UW UT WOS:000297226000003 PM 21768444 ER PT J AU Wan, J Abuabara, K Kurd, SK Musiek, A Steinemann, JM Vittorio, CC Gelfand, JM AF Wan, Joy Abuabara, Katrina Kurd, Shanu K. Musiek, Amy Steinemann, Jane M. Vittorio, Carmela C. Gelfand, Joel M. TI Reliability and Validity of a Photographic Method for Measuring Facial Hair Density in Men SO ARCHIVES OF DERMATOLOGY LA English DT Letter C1 [Wan, Joy; Abuabara, Katrina; Kurd, Shanu K.; Musiek, Amy; Steinemann, Jane M.; Vittorio, Carmela C.; Gelfand, Joel M.] Univ Penn, Dept Dermatol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Abuabara, Katrina; Kurd, Shanu K.] Univ Penn, Dept Internal Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gelfand, Joel M.] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Musiek, Amy] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Gelfand, JM (reprint author), 1471 Penn Tower,1 Convent Ave, Philadelphia, PA 19104 USA. EM Joel.Gelfand@uphs.upenn.edu FU NIAMS NIH HHS [T32-AR07465, T32 AR007465] NR 5 TC 1 Z9 1 U1 0 U2 0 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 NOV PY 2011 VL 147 IS 11 BP 1328 EP 1329 PG 2 WC Dermatology SC Dermatology GA 850UW UT WOS:000297226000020 PM 22106126 ER PT J AU Rosenbaum, JT Davey, MP AF Rosenbaum, James T. Davey, Michael P. TI Time for a Gut Check: Evidence for the Hypothesis That HLA-B27 Predisposes to Ankylosing Spondylitis by Altering the Microbiome SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID ACUTE ANTERIOR UVEITIS; HUMAN MONOCYTIC CELLS; IMMUNE-RESPONSE; TRANSGENIC RATS; T-CELLS; DISEASE; KLEBSIELLA; BACTERIA; ARTHRITIS; PEPTIDES C1 [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Davey, Michael P.] Portland VA Med Ctr, Portland, OR USA. RP Rosenbaum, JT (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,L467Ad, Portland, OR 97239 USA. EM rosenbaj@ohsu.edu FU NEI NIH HHS [R01 EY019604, R01 EY019604-01, R01-EY-019604] NR 44 TC 24 Z9 26 U1 1 U2 17 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 NOV PY 2011 VL 63 IS 11 BP 3195 EP 3198 DI 10.1002/art.30558 PG 4 WC Rheumatology SC Rheumatology GA 850TC UT WOS:000297221100002 PM 21792826 ER PT J AU Shahouri, SH Michaud, K Mikuls, TR Caplan, L Shaver, TS Anderson, JD Weidensaul, DN Busch, RE Wang, S Wolfe, F AF Shahouri, Shadi H. Michaud, Kaleb Mikuls, Ted R. Caplan, Liron Shaver, Timothy S. Anderson, James D. Weidensaul, David N. Busch, Ruth E. Wang, Shirley Wolfe, Frederick TI Remission of Rheumatoid Arthritis in Clinical Practice Application of the American College of Rheumatology/European League Against Rheumatism 2011 Remission Criteria SO ARTHRITIS AND RHEUMATISM LA English DT Article ID HEALTH-ASSESSMENT QUESTIONNAIRE; MULTILEVEL LOGISTIC-REGRESSION; DISEASE-ACTIVITY SCORE; TRIALS; DEFINITION; AGREEMENT; INDEX; CARE AB Objective. To describe use of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) remission criteria in clinical practice. Methods. Remission was examined using data on 1,341 patients with RA (91% men) from the US Department of Veterans Affairs RA (VARA) registry (total of 9,700 visits) and 1,153 patients with RA (25.8% men) in a community rheumatology practice (Arthritis and Rheumatology Clinics of Kansas [ARCK]) (total of 6,362 visits). Cross-sectional and cumulative probabilities were studied, and agreement between the various remission criteria was assessed. Aspects of reliability of the criteria were determined using Boolean-based definitions, as well as the Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) scoring methods proposed by the ACR/EULAR joint committee. Results. When the 3-variable ACR/EULAR definition of remission recommended for use in community practice (swollen and tender joint counts <= 1, and visual analog scale score for patient's global assessment of disease activity <= 1) was applied, cross-sectional remission was 7.5% (95% confidence interval [95% CI] 6.4, 8.7%) for ARCK and 8.9% (95% CI 7.9, 9.9%) for VARA, and cumulative remission (remission at any observation) was 18.0% (for ARCK) and 24.4% (for VARA), over a mean followup of similar to 2.2 years. Addition of the erythrocyte sedimentation rate or C-reactive protein level to the criteria set reduced remission to 5.0-6.2%, and use of the CDAI/SDAI increased the proportions to 6.9-10.1%. Moreover, 1.8-4.6% of the patients met remission criteria at >= 2 visits. Agreement between criteria definitions was good, as assessed by kappa statistics and Jaccard coefficients. Among patients in remission, the probability of a remission lasting 2 years was 6.0-14.1%. Among all patients, the probability of a remission lasting 2 years was <3%. Remission status and examination results for each patient varied substantially among physicians, as determined by multilevel analyses. Conclusion. Cross-sectional remission occurred in 5.0-10.1% of the patients in these cohorts, with cumulative remission being 2-3 times greater; however, long-term remission was rare. Problems with reliability and agreement limit the usefulness of these criteria in the individual patient. However, the criteria can be an effective method for measuring clinical status and treatment effect in groups of patients in the community. C1 [Michaud, Kaleb; Wolfe, Frederick] Natl Data Bank Rheumat Dis, Wichita, KS 67214 USA. [Shahouri, Shadi H.; Shaver, Timothy S.; Anderson, James D.; Weidensaul, David N.; Busch, Ruth E.; Wang, Shirley] Arthrit Clin Kansas, Wichita, KS USA. [Shahouri, Shadi H.; Shaver, Timothy S.; Anderson, James D.; Weidensaul, David N.; Busch, Ruth E.; Wang, Shirley] Rheumatol Clin Kansas, Wichita, KS USA. [Shahouri, Shadi H.; Shaver, Timothy S.; Anderson, James D.; Weidensaul, David N.; Wang, Shirley; Wolfe, Frederick] Univ Kansas, Sch Med, Wichita, KS 67214 USA. [Michaud, Kaleb] Univ Nebraska Med Ctr, Omaha, NE USA. [Mikuls, Ted R.] Omaha VA Med Ctr, Omaha, NE USA. [Mikuls, Ted R.] Univ Nebraska, Omaha, NE 68182 USA. [Caplan, Liron] Denver VA Med Ctr, Denver, CO USA. [Caplan, Liron] Univ Colorado, Denver, CO 80202 USA. [Busch, Ruth E.] Wichita State Univ, Wichita, KS USA. RP Wolfe, F (reprint author), Natl Data Bank Rheumat Dis, 1035 N Emporia,Suite 288, Wichita, KS 67214 USA. EM fwolfe@arthritis-research.org FU VA Health Services Research & Development Service; Arthritis Foundation; NIH [1RC1AR058601-01]; VA Merit grant; VA Career Development Award [CDA 07-221] FX The US VA Rheumatoid Arthritis registry is supported by the VA Health Services Research & Development Service. Dr. Michaud's work was supported in part by an Arthritis Foundation New Investigator Award and a grant from the NIH (American Recovery & Reinvestment Act grant 1RC1AR058601-01). Dr. Mikuls' work was supported by a VA Merit grant. Dr. Caplan's work was supported by a VA Career Development Award (CDA 07-221). NR 29 TC 42 Z9 43 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 NOV PY 2011 VL 63 IS 11 BP 3204 EP 3215 DI 10.1002/art.30524 PG 12 WC Rheumatology SC Rheumatology GA 850TC UT WOS:000297221100004 PM 21739423 ER PT J AU Bartels, CM Everett, C McBride, P Smith, M Kind, AJH Mell, M AF Bartels, Christie M. Everett, Christine McBride, Patrick Smith, Maureen Kind, Amy J. H. Mell, Matthew TI Is the "lipid paradox" in rheumatoid arthritis really a paradox? Comment on the article by Bartels et al Reply SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID MORTALITY C1 [Bartels, Christie M.; Everett, Christine; McBride, Patrick; Smith, Maureen; Kind, Amy J. H.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 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, Madison, WI 53706 USA. NR 6 TC 1 Z9 1 U1 0 U2 2 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 NOV PY 2011 VL 63 IS 11 BP 3645 EP 3646 DI 10.1002/art.30587 PG 2 WC Rheumatology SC Rheumatology GA 850TC UT WOS:000297221100061 ER PT J AU Anderson, JK Zimmerman, L Caplan, L Michaud, K AF Anderson, Jaclyn K. Zimmerman, Lani Caplan, Liron Michaud, Kaleb TI Measures of Rheumatoid Arthritis Disease Activity Patient (PtGA) and Provider (PrGA) Global Assessment of Disease Activity, Disease Activity Score (DAS) and Disease Activity Score With 28-Joint Counts (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Patient Activity Score (PAS) and Patient Activity Score-II (PASII), Routine Assessment of Patient Index Data (RAPID), Rheumatoid Arthritis Disease Activity Index (RADAI) and Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5), Chronic Arthritis Systemic Index (CASI), Patient-Based Disease Activity Score With ESR (PDAS1) and Patient-Based Disease Activity Score Without ESR (PDAS2), and Mean Overall Index for Rheumatoid Arthritis (MOI-RA) SO ARTHRITIS CARE & RESEARCH LA English DT Article ID HEALTH-ASSESSMENT QUESTIONNAIRE; COLLEGE-OF-RHEUMATOLOGY; VISUAL ANALOG SCALES; RANDOMIZED CONTROLLED-TRIALS; ACUTE-PHASE REACTANTS; FORMAL JOINT COUNTS; CORE SET MEASURES; RESPONSE CRITERIA; FUNCTIONAL-CAPACITY; IMPROVEMENT CRITERIA C1 [Anderson, Jaclyn K.; Zimmerman, Lani; Michaud, Kaleb] Univ Nebraska Med Ctr, Omaha, NE USA. [Anderson, Jaclyn K.] Abbott Labs, Abbott Pk, IL USA. [Caplan, Liron] Denver Vet Affairs Med Ctr, Denver, CO USA. [Caplan, Liron] Univ Colorado, Sch Med, Aurora, CO USA. [Michaud, Kaleb] Natl Data Bank Rheumat Dis, Wichita, KS USA. RP Anderson, JK (reprint author), 200 Abbott Pk Rd,Dept R4NE,Bldg AP34-1, Abbott Pk, IL 60064 USA. EM Jaclyn.Anderson@abbott.com OI Anderson, Jaclyn/0000-0002-0893-3900 FU American College of Rheumatology FX Supported in part by the American College of Rheumatology. NR 121 TC 41 Z9 44 U1 0 U2 10 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 NOV PY 2011 VL 63 SU 11 BP S14 EP S36 DI 10.1002/acr.20621 PG 23 WC Rheumatology SC Rheumatology GA 850SR UT WOS:000297219500003 PM 22588741 ER PT J AU Rider, LG Werth, VP Huber, AM Alexanderson, H Rao, AP Ruperto, N Herbelin, L Barohn, R Isenberg, D Miller, FW AF Rider, Lisa G. Werth, Victoria P. Huber, Adam M. Alexanderson, Helene Rao, Anand Prahalad Ruperto, Nicolino Herbelin, Laura Barohn, Richard Isenberg, David Miller, Frederick W. TI Measures of Adult and Juvenile Dermatomyositis, Polymyositis, and Inclusion Body Myositis Physician and Patient/Parent Global Activity, Manual Muscle Testing (MMT), Health Assessment Questionnaire (HAQ)/Childhood Health Assessment Questionnaire (C-HAQ), Childhood Myositis Assessment Scale (CMAS), Myositis Disease Activity Assessment Tool (MDAAT), Disease Activity Score (DAS), Short Form 36 (SF-36), Child Health Questionnaire (CHQ), Physician Global Damage, Myositis Damage Index (MDI), Quantitative Muscle Testing (QMT), Myositis Functional Index-2 (FI-2), Myositis Activities Profile (MAP), Inclusion Body Myositis Functional Rating Scale (IBMFRS), Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), Cutaneous Assessment Tool (CAT), Dermatomyositis Skin Severity Index (DSSI), Skindex, and Dermatology Life Quality Index (DLQI) SO ARTHRITIS CARE & RESEARCH LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHIES; SYSTEMIC-LUPUS-ERYTHEMATOSUS; MUSCULAR-DYSTROPHY FSHD; RANDOMIZED PILOT TRIAL; HOME EXERCISE PROGRAM; OF-LIFE; PEDIATRIC RHEUMATOLOGY; NATURAL-HISTORY; PROGNOSTIC-FACTORS; INTERNATIONAL CONSENSUS C1 [Rider, Lisa G.] NIEHS, Environm Autoimmun Grp, Program Clin Res, NIH, Bethesda, MD 20892 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Werth, Victoria P.] Univ Penn, Philadelphia, PA 19104 USA. [Huber, Adam M.] Dalhousie Univ, Halifax, NS, Canada. [Huber, Adam M.] IWK Hlth Ctr, Halifax, NS, Canada. [Alexanderson, Helene] Karolinska Inst, Stockholm, Sweden. [Alexanderson, Helene] Karolinska Univ Hosp, Stockholm, Sweden. [Rao, Anand Prahalad; Ruperto, Nicolino] IRCCS G Gaslini, Paediat Rheumatol Int Trials Org, Genoa, Italy. [Herbelin, Laura; Barohn, Richard] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Isenberg, David] UCL, London, England. RP Rider, LG (reprint author), NIEHS, Environm Autoimmun Grp, Program Clin Res, NIH, CRC 4-2352,MSC 1301,10 Ctr Dr, Bethesda, MD 20892 USA. EM rider1@mail.nih.gov OI Rider, Lisa/0000-0002-6912-2458 FU NIH National Institute of Environmental Health Sciences FX Supported in part by the Intramural Research Program of the NIH National Institute of Environmental Health Sciences. NR 112 TC 51 Z9 54 U1 2 U2 10 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD NOV PY 2011 VL 63 SU 11 BP S118 EP S157 DI 10.1002/acr.20532 PG 40 WC Rheumatology SC Rheumatology GA 850SR UT WOS:000297219500011 PM 22588740 ER PT J AU Huang, SN Chen, HH Yuan, HS Dai, GP Schuhle, DT Mekkaoui, C Ngoy, S Liao, RL Caravan, P Josephson, L Sosnovik, DE AF Huang, Shuning Chen, Howard H. Yuan, Hushan Dai, Guangping Schuhle, Daniel T. Mekkaoui, Choukri Ngoy, Soeun Liao, Ronglih Caravan, Peter Josephson, Lee Sosnovik, David E. TI Molecular MRI of Acute Necrosis With a Novel DNA-Binding Gadolinium Chelate Kinetics of Cell Death and Clearance in Infarcted Myocardium SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE molecular imaging; MRI; necrosis; myocardium; infarction ID ENHANCED MAGNETIC-RESONANCE; NECROTIC CELLS; CONTRAST AGENTS; MECHANISMS; APOPTOSIS; DISEASE; HEART; RATS; TC-99M-ANNEXIN-V; REPERFUSION AB Background-Current techniques to image cell death in the myocardium are largely nonspecific. We report the use of a novel DNA-binding gadolinium chelate (Gd-TO) to specifically detect the exposed DNA in acutely necrotic (ruptured) cells in vivo. Methods and Results-In vivo MRI was performed in 20 mice with myocardial infarction (MI). The mice were injected with Gd-TO or Gd-DTPA at varying time points after MI. MRI was performed 2 hours after probe injection, to avoid nonspecific signal from the late gadolinium enhancement effect. Cell rupture (Gd-TO uptake) was present within 2 hours of infarction but peaked 9 to 18 hours after the onset of injury. A significant increase in the longitudinal relaxation rate (R(1)) in the infarct was seen in mice injected with Gd-TO within 48 hours of MI, but not in those injected more than 72 hours after MI (R(1)=1.24 +/- 0.08 and 0.92 +/- 0.03 s(-1), respectively, P<0.001). Gd-DTPA, unlike Gd-TO, washed completely out of acute infarcts within 2 hours of injection (P<0.001). The binding of Gd-TO to exposed DNA in acute infarcts was confirmed with fluorescence microscopy. Conclusions-Gd-TO specifically binds to acutely necrotic cells and can be used to image the mechanism and chronicity of cell death in injured myocardium. Cell rupture in acute MI begins early but peaks many hours after the onset of injury. The ruptured cells are efficiently cleared by the immune system and are no longer present in the myocardium 72 hours after injury. (Circ Cardiovasc Imaging. 2011;4:729-737.) C1 [Huang, Shuning; Chen, Howard H.; Dai, Guangping; Schuhle, Daniel T.; Mekkaoui, Choukri; Caravan, Peter; Josephson, Lee; Sosnovik, David E.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Martinos Ctr Biomed Imagin, Boston, MA 02115 USA. [Chen, Howard H.; Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. [Yuan, Hushan; Josephson, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Translat Nucl Med & Mol Imaging, Boston, MA USA. [Ngoy, Soeun; Liao, Ronglih] Harvard Univ, Sch Med, Brigham & Womans Hosp, Div Cardiol, Boston, MA USA. [Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Sosnovik, DE (reprint author), 149 13th St, Charlestown, MA 02129 USA. EM sosnovik@nmr.mgh.harvard.edu FU National Institutes of Health [R01 HL093038, R01 EB011996, S10RR025563, P41RR14075] FX This study was funded by the following National Institutes of Health grants: R01 HL093038 (Dr Sosnovik), R01 EB011996 (Dr Josephson), S10RR025563 (Dr Dai), and P41RR14075 (Martinos Center). NR 36 TC 24 Z9 24 U1 1 U2 9 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 NOV PY 2011 VL 4 IS 6 BP 729 EP U186 DI 10.1161/CIRCIMAGING.111.966374 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 850AZ UT WOS:000297168100019 PM 21836081 ER PT J AU Yeh, RW Mauri, L AF Yeh, Robert W. Mauri, Laura TI Choosing Methods to Minimize Confounding in Observational Studies Do the Ends Justify the Means? SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Editorial Material DE Editorials; comparative effectiveness; confounding; bias; stents; instrumental variables; propensity scores ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY DISEASE; BARE-METAL STENTS; INSTRUMENTAL VARIABLES; RANDOMIZED-TRIALS; OUTCOMES RESEARCH; MEDICAL THERAPY; SAFETY; ANGIOPLASTY; EFFICACY C1 [Yeh, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA. [Mauri, Laura] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. RP Mauri, L (reprint author), 75 Francis St, Boston, MA 02115 USA. EM lmauri1@partners.org NR 15 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2011 VL 4 IS 6 BP 581 EP 583 DI 10.1161/CIRCOUTCOMES.111.963538 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 850BC UT WOS:000297168400002 PM 22085982 ER PT J AU Melloni, C Roe, MT Chen, AY Wang, TY Wiviott, SD Ho, PM Peterson, ED Alexander, KP AF Melloni, Chiara Roe, Matthew T. Chen, Anita Y. Wang, Tracy Y. Wiviott, Stephen D. Ho, P. Michael Peterson, Eric D. Alexander, Karen P. TI Use of Early Clopidogrel by Reperfusion Strategy Among Patients Presenting With ST-Segment Elevation Myocardial Infarction SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE clopidogrel; guideline adherence; fibrinolysis; reperfusion ID PERCUTANEOUS CORONARY INTERVENTION; PLACEBO-CONTROLLED TRIAL; FIBRINOLYTIC THERAPY; ASPIRIN; PRETREATMENT; OUTCOMES; RISK AB Background-The 2007 update of the ACC/AHA guidelines for STEMI patients recommended addition of clopidogrel to aspirin regardless of reperfusion strategy, with a bolus dose in patients <75 years of age. Methods and Results-We evaluated use and dose of early clopidogrel among 52,140 STEMI patients enrolled in 368 hospitals participating in NCDR's ACTION Registry (R)-Get with the Guidelines (GWTG (TM)) from January 2007-September 2009. Patients were stratified by reperfusion strategy: primary percutaneous coronary intervention (PCI, n = 37,108), fibrinolysis (n = 5805), or no-reperfusion (n = 9227), and by age (<75 or >= 75 years). Adjusted odds for in-hospital outcomes are reported by clopidogrel use across reperfusion strategies. Clopidogrel was administered early to 97% of primary PCI, 18% of fibrinolytic, and 6% of non-reperfused patients. Among patients receiving clopidogrel, a loading dose (>= 300 mg) was often used in primary PCI (91%) but less frequently among fibrinolysis-treated (83%) and non-reperfused patients (74%). A positive time trend from Q1 2007-Q3 2009 in overall clopidogrel use was observed only in fibrinolytic patients (15-20%) Use of clopidogrel was associated with a significant increase in major bleeding only among older patients in the no-reperfusion group (21.9% vs. 13.2%; OR 2.19; 95% CI 1.47-3.27). A significantly lower risk of in-hospital death was associated with clopidogrel use across all reperfusion strategies (OR [95% CI], primary PCI: 0.15 [0.13-0.19]; fibrinolysis: 0.26 [0.12-0.57]; no reperfusion: 0.42 [0.27-0.65]). Conclusion-Early clopidogrel use has not yet extended to the routine care of STEMI patients treated with fibrinolysis or those not receiving reperfusion as recommended in the guideline update. (Circ Cardiovasc Qual Outcomes. 2011;4:603-609.) C1 [Melloni, Chiara; Roe, Matthew T.; Chen, Anita Y.; Wang, Tracy Y.; Peterson, Eric D.; Alexander, Karen P.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. [Melloni, Chiara; Roe, Matthew T.; Chen, Anita Y.; Wang, Tracy Y.; Peterson, Eric D.; Alexander, Karen P.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27705 USA. [Wiviott, Stephen D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ho, P. Michael] Denver VA Med Ctr, Cardiol Sect, Denver, CO USA. Univ Colorado Denver, Denver, CO USA. RP Melloni, C (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA. EM mello004@mc.duke.edu FU Bristol-Myers Squibb (BMS)/Sanofi Pharmaceuticals Partnership; Schering-Plough Corporation; BMS/Sanofi-Aventis; BMS/Sanofi Partnership; Merck/Schering-Plough; AstraZeneca; BMS; Ortho; McNeil; Pfizer; Sanofi-Aventis; Daiichi Sankyo; Eli Lilly; Schering-Plough; VA Research & Development Career Development Award [05-026-2] FX The Bristol-Myers Squibb (BMS)/Sanofi Pharmaceuticals Partnership and Schering-Plough Corporation are founding sponsors of the ACTION Registry-GWTG. Dr Roe receives research grants from BMS/Sanofi-Aventis and Merck/Schering-Plough, is on the speaker's bureau for BMS/Sanofi-Aventis and Merck/Schering-Plough, and consults for Merck/Schering-Plough; Dr Wang receives research grants from BMS/Sanofi Partnership and Merck/Schering-Plough; Dr Wiviott receives honoraria for educational presentations from BMS, Daiichi Sankyo, Eli Lilly, Schering-Plough, Merck, and The Medicine's Company, receives consulting fees from AstraZeneca, BMS, Ortho McNeil, Pfizer, and Sanofi-Aventis, and research grants from Daiichi Sankyo, Eli Lilly, and Schering-Plough; Dr Ho receives research support from a VA Research & Development Career Development Award (05-026-2) and is also a consultant for Wellpoint, Inc; and Dr Peterson receives research grants from BMS. NR 17 TC 2 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2011 VL 4 IS 6 BP 603 EP 609 DI 10.1161/CIRCOUTCOMES.111.961045 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 850BC UT WOS:000297168400006 PM 21988922 ER PT J AU Eapen, ZJ Fonarow, GC Dai, D O'Brien, SM Schwamm, LH Cannon, CP Heidenreich, PA Bhatt, DL Peterson, ED Hernandez, AF AF Eapen, Zubin J. Fonarow, Gregg C. Dai, David O'Brien, Sean M. Schwamm, Lee H. Cannon, Christopher P. Heidenreich, Paul A. Bhatt, Deepak L. Peterson, Eric D. Hernandez, Adrian F. CA Get Guidelines Steering Comm Hosp TI Comparison of Composite Measure Methodologies for Rewarding Quality of Care An Analysis From the American Heart Association's Get With The Guidelines Program SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE composite performance measure; coronary artery disease; outcomes research ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; PERFORMANCE-MEASURES; CLINICAL-OUTCOMES; HOSPITAL QUALITY; MORTALITY; CARDIOLOGY; SURGERY; TRENDS AB Background-Composite indices of health care performance are an aggregation of underlying individual performance measures and are increasingly being used to rank hospitals. We sought to conduct an observational analysis to determine the influence of the opportunity-based and all-or-none composite performance measures on hospital rankings. Methods and Results-We examined 194 245 patients hospitalized with acute myocardial infarction between July 2006 and June 2009 from 334 hospitals participating in the Get With The Guidelines-Coronary Artery Disease (GWTG-CAD) quality improvement program. We analyzed hospital opportunity-based and all-or-none composite scores and 30-day risk-standardized all-cause mortality and readmission rates. We found that the median calculated opportunity-based score for these hospitals was 95.5 (interquartile range, 90.4, 98.0). The median all-or-none score was 88.9 (interquartile range, 79.7, 94.4). The 2 scoring methods were significantly correlated with one another (r=0.98, P<0.001). Rankings generated by the two methods were significantly correlated (r=0.93, P<0.001). The two methods had a modest correlation with the 30-day risk-standardized mortality rate (opportunity-based score: r=-0.25, P<0.001; all-or-none score: r=-0.24, P<0.001). Neither composite measure correlated with the 30-day risk-standardized readmission rate. Over time, the number of hospitals new to the top and bottom quintiles of hospital rankings diminished similarly for both composite measures. When including additional performance measures into the composite score, the two methods produced similar changes in hospital rankings. Conclusions-The opportunity-based and all-or-none coronary artery disease composite indices are highly correlated and yield similar ranking of the top and bottom quintiles of hospitals. The two methods provide similarly modest correlations with 30-day mortality, but not readmission. (Circ Cardiovasc Qual Outcomes. 2011;4:610-618.) C1 [Eapen, Zubin J.; Dai, David; O'Brien, Sean M.; Peterson, Eric D.; Hernandez, Adrian F.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27715 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cannon, Christopher P.; Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Heidenreich, Paul A.] Vet Affairs Palo Alto Healthcare Syst, Div Cardiol, Palo Alto, CA USA. [Bhatt, Deepak L.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. RP Hernandez, AF (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM adrian.hernandez@duke.edu RI O'Brien, Sean/H-6268-2013; Hernandez, Adrian F./A-7818-2016 OI Heidenreich, Paul/0000-0001-7730-8490; Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU Merck/Schering-Plough Partnership; American Heart Association-Pharmaceutical Roundtable [0875142N]; David and Stevie Spina; Agency for Healthcare Research and Quality (AHRQ) [U18HS016964]; National Heart, Lung, and Blood Institute; Accumetrics; AstraZeneca; GlaxoSmithKline; InteKrin Therapeutics; Merck; Takeda; Medtronic; Astra Zeneca; Bristol-Myers Squibb; Eisai; Sanofi Aventis; Johnson Johnson; Amylin FX Get With the Guidelines-Coronary Artery Disease is a program of the American Heart Association and is supported in part by an unrestricted educational grant from Merck/Schering-Plough Partnership, which did not participate in the design or analysis of the study or in manuscript preparation. This work was supported by an award from the American Heart Association-Pharmaceutical Roundtable and David and Stevie Spina. Dr Eapen received funding from an American Heart Association-Pharmaceutical Roundtable outcomes training grant (0875142N). This project received infrastructure support from the Agency for Healthcare Research and Quality (AHRQ), under grant No. U18HS016964. The content is solely the responsibility of the authors and does not necessarily represent the official views of the AHRQ. The funding source had no role in the design or implementation of the study or in the decision to seek publication.; Dr Fonarow reports receiving research support from the National Heart, Lung, and Blood Institute (significant) and the Agency for Healthcare Research and Quality (significant). Dr Fonarow reports receiving consulting support from Medtronic (modest) and Novartis (significant). Dr Schwamm reports serving as Chair of the Get With The Guidelines National Steering Committee (unpaid). Dr Schwamm reports receiving consulting support from Stroke Systems, Massachusetts Department of Public Health. Dr Cannon reports receiving research support from Accumetrics, AstraZeneca, GlaxoSmithKline, InteKrin Therapeutics, Merck, and Takeda. Dr Cannon serves on the advisory board of Alnylam, Bristol-Myers Squibb/Sanofi Partnership, Novartis. Dr Cannon serves as a clinical advisor for and has equity in Automedics Medical Systems. Dr Heidenreich reports receiving research support from Medtronic. Dr Bhatt reports receiving research support from Astra Zeneca, Bristol-Myers Squibb, Eisai, Sanofi Aventis, and The Medicines Company. Dr Peterson serves as the principal investigator for the American Heart Association for GWTG data analysis. Dr Hernandez reports receiving research support from Johnson & Johnson and Amylin. NR 22 TC 12 Z9 13 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2011 VL 4 IS 6 BP 610 EP 618 DI 10.1161/CIRCOUTCOMES.111.961391 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 850BC UT WOS:000297168400007 PM 22010200 ER PT J AU Kim, YY Gauvreau, K Bacha, EA Landzberg, MJ Benavidez, OJ AF Kim, Yuli Y. Gauvreau, Kimberlee Bacha, Emile A. Landzberg, Michael J. Benavidez, Oscar J. TI Resource Use Among Adult Congenital Heart Surgery Admissions in Pediatric Hospitals Risk Factors for High Resource Utilization and Association With Inpatient Death SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE heart defects; congenital; surgery; risk factors; resource utilization ID ARTERY-BYPASS-SURGERY; SURGICAL CASE VOLUMES; CARDIAC-SURGERY; MORTALITY-RATES; HEALTH-CARE; GRAFT-SURGERY; DISEASE; DEPRESSION; ANXIETY; COMORBIDITY AB Background-Pediatric hospitals frequently perform congenital heart surgery in adults with congenital heart disease. The impact of these admissions on pediatric hospital resources is unknown. Our goals were to examine resource use by adults undergoing congenital heart surgery in pediatric hospitals, explore the association between high resource use (HRU) and inpatient death, and identify HRU risk factors. Methods and Results-We obtained inpatient data from 42 pediatric hospitals from 2000 to 2008 and selected adult congenital heart (ACH) surgery admissions. We defined HRU admissions as those exceeding the 90th percentile for total hospital charges. We performed multivariable analyses using generalized estimating equations to identify risk factors for HRU. Of 97 563 congenital heart surgery admissions to pediatric hospitals, 3061 (3.1%) were adults, accounting for 2.2% of total hospital charges. The threshold for HRU was total hospital charges >=$213 803. Although HRU admissions comprised 10% of admissions, they accounted for 34% of charges for all ACH surgery admissions. Mortality rate was 16% for HRU admissions and 0.7% for others (P<0.001). Multivariable analysis demonstrated higher case complexity: risk category 2 (adjusted odds ratio [AOR], 3.6; P=0.02), risk category 3 (AOR, 13.7; P<0.001), and risk category 4 + (AOR, 30.7; P<0.001) as compared with risk category 1; DiGeorge syndrome (AOR, 4.2; P=0.006); depression (AOR, 3.1; P<0.001); weekend admission (AOR, 2.6; P<0.001); and government insurance (AOR, 2.0; P<0.001) as risk factors for HRU. Conclusions-High resource use ACH surgery admissions are associated with significantly greater mortality rates. ACH admissions with greater surgical complexity, government insurance, DiGeorge syndrome, weekend admission, and depression were more likely to result in HRU. (Circ Cardiovasc Qual Outcomes. 2011;4:634-639.) C1 [Gauvreau, Kimberlee; Landzberg, Michael J.; Benavidez, Oscar J.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Cardiol, Boston, MA 02115 USA. [Kim, Yuli Y.] Univ Penn, Sch Med, Hosp Univ Penn, Div Cardiol, Philadelphia, PA 19104 USA. [Kim, Yuli Y.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. [Landzberg, Michael J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Benavidez, Oscar J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Pediat Congenital Cardiol, Boston, MA 02115 USA. [Bacha, Emile A.] Columbia Univ, Coll Phys & Surg, Morgan Stanley Childrens Hosp New York, Dept Surg, New York, NY USA. RP Benavidez, OJ (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. EM Oscar.Benavidez@cardio.chboston.org FU Dunlevie Family Endowed Fund; Robert Wood Johnson, Harold Amos Medical Faculty; Children's Hospital Boston Department of Cardiology FX This study was supported in part by the Dunlevie Family Endowed Fund for Adult Congenital Heart Disease, Boston, MA. Dr Benavidez was supported by the Robert Wood Johnson, Harold Amos Medical Faculty Program and the Children's Hospital Boston Department of Cardiology. NR 40 TC 14 Z9 16 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2011 VL 4 IS 6 BP 634 EP 639 DI 10.1161/CIRCOUTCOMES.111.963223 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 850BC UT WOS:000297168400010 PM 22010202 ER PT J AU McDonald, WM Durkalski, V Ball, ER Holtzheimer, PE Pavlicova, M Lisanby, SH Avery, D Anderson, BS Nahas, Z Zarkowski, P Sackeim, HA George, MS AF McDonald, William M. Durkalski, Valerie Ball, Edward R., III Holtzheimer, Paul E., III Pavlicova, Martina Lisanby, Sarah H. Avery, David Anderson, Berry S. Nahas, Ziad Zarkowski, Paul Sackeim, Harold A. George, Mark S. TI IMPROVING THE ANTIDEPRESSANT EFFICACY OF TRANSCRANIAL MAGNETIC STIMULATION: MAXIMIZING THE NUMBER OF STIMULATIONS AND TREATMENT LOCATION IN TREATMENT-RESISTANT DEPRESSION SO DEPRESSION AND ANXIETY LA English DT Article DE transcranial magnetic stimulation; rTMS; high frequency rTMS; low frequency rTMS; treatment-resistant depression ID ASTERISK-D REPORT; MAJOR DEPRESSION; CONTROLLED-TRIAL; DISORDER; OUTPATIENTS; THERAPY AB Objective: To assess the efficacy of increasing the number of fast left repetitive transcranial magnetic stimulations (rTMS) (10 Hz @ 120% of motor threshold (MT) over the left dorsolateral prefrontal cortex (DLPFC)) needed to achieve remission in treatment-resistant depression (TRD). And, to determine if patients who do not remit to fast left will remit using slow right rTMS (1 Hz @ 120% MTover the right DLPFC). Method: Patients were part of a multicenter sham-controlled trial investigating the efficacy of fast left rTMS. Patients who failed to meet minimal response criteria in the sham-controlled study could enroll in this open fast left rTMS study for an additional 3-6 weeks. Patients who failed to remit to fast left could switch to slow right rTMS for up to 4 additional weeks. The final outcome measure was remission, defined as a HAM-D score of < 3 or 2 consecutive HAM-D scores less than 10. Results: Forty-three of 141 (30.5%) patients who enrolled in the open phase study eventually met criteria for remission. Patients who remitted during fast left treatment received a mean of 26 active treatments (90,000 pulses). Twenty-six percent of patients who failed fast left remitted during slow right treatment. Conclusion: The total number of rTMS stimulations needed to achieve remission in TRD may be higher than is used in most studies. TRD patients who do not respond to fast left rTMS may remit to slow right rTMS or additional rTMS stimulations. Depression and Anxiety 28: 973-980, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [McDonald, William M.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30329 USA. [Durkalski, Valerie; Ball, Edward R., III] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Pavlicova, Martina] Columbia Univ Coll Phys & Surg, Dept Biostat, New York, NY 10032 USA. [Lisanby, Sarah H.] Duke Univ, Dept Psychiat, Durham, NC 27706 USA. [Avery, David; Zarkowski, Paul] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Anderson, Berry S.; Nahas, Ziad; George, Mark S.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Sackeim, Harold A.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [George, Mark S.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP McDonald, WM (reprint author), Emory Univ, Sch Med, Dept Psychiat & Behav Sci, 1841 Clifton Rd NE, Atlanta, GA 30329 USA. EM wmcdona@emory.edu RI Holtzheimer, Paul/B-6212-2015 OI Holtzheimer, Paul/0000-0002-3552-3296 FU National Institute of Mental Health (NIMH) [5R01MH069929, 5R01MH069887, 5R01MH069896, 5R01MH069895, 5R01MH069886]; St. Jude Medical Neuromodulation; AvaCat Consulting; Tetragenex; Neuronetics; Advanced Neuromodulatory Systems; Brainsway; Cyberonics; Takeda; MECTA Corporation; Medtronic; PureTech Ventures; NeoStim and NeoSync; Brainsonix; Cephos FX This study was supported by the National Institute of Mental Health (NIMH) as the Optimization of TMS for the Treatment of Depression Study (OPT-TMS) involving grants 5R01MH069929 (Dr. Avery), 5R01MH069887 (Dr. George), 5R01MH069896 (Dr. George), 5R01MH069895 (Dr. Lisanby), and 5R01MH069886 (Dr. McDonald).; The authors disclose the following financial relationships within the past 3 years: Following a competitive bid and request involving all TMS manufacturers at the time of trial initiation, Neuronetics Inc. was selected and loaned the TMS devices, head holders, and coils for the trial and allowed use of the safety Investigational Device Exemption for their device. Neuronetics did not provide any financial support for the study which was funded by the NIMH. Potential conflicts are reported over the past 3 years. Dr. McDonald is presently an unpaid consultant to NeoStim. Dr. Holtzheimer reports consulting fees from St. Jude Medical Neuromodulation, AvaCat Consulting, and Tetragenex, and is an unpaid consultant to NeoStim. Drs. McDonald and Holtzheimer are faculty at Emory University which holds a patent on TMS technology. Neither received royalties or is involved in the development or promotion of this patent. Dr. Lisanby reports research grants, speaking fees, or advisory board work with Neuronetics, Advanced Neuromodulatory Systems, Brainsway, and Cyberonics. Dr. Lisanby has a patent application with Columbia University on neuromodulation technology for which she receives no royalties or compensation. Dr. Avery has received research support from Neuronetics and Takeda, has been a consultant for Neuronetics and has been on the speaker's bureau for Eli Lilly, Takeda and Forest Pharmaceuticals. Dr. Nahas reports past and current research grants, speaking fees or consulting work with Cyberonics, Neuronetics, MECTA Corporation, and Medtronic. Dr. Nahas has acted as an unpaid consultant for Neuropace. Dr. Sackeim received consultant fees from MECTA Corporation and Cyberonics. Dr. George received consultant fees from PureTech Ventures and reports research grants, speaking fees, or advisory work with Brainsway, Mecta Corporation, Neuronetics, Cephos, NeoStim and NeoSync, Brainsonix, Cyberonics, and Cephos. Dr. George is faculty at MUSC which has two patent applications in Dr. George's name combining MRI and TMS. NR 16 TC 34 Z9 36 U1 0 U2 12 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 NOV PY 2011 VL 28 IS 11 BP 973 EP 980 DI 10.1002/da.20885 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 850TH UT WOS:000297221800005 PM 21898711 ER PT J AU Deckersbach, T Moshier, SJ Tuschen-Caffier, B Otto, MW AF Deckersbach, Thilo Moshier, Samantha J. Tuschen-Caffier, Brunna Otto, Michael W. TI MEMORY DYSFUNCTION IN PANIC DISORDER: AN INVESTIGATION OF THE ROLE OF CHRONIC BENZODIAZEPINE USE SO DEPRESSION AND ANXIETY LA English DT Article DE anxiety disorders; anxiolytic; benzodiazepine; tests; neuropsychological; psychopharmacology; memory; short term; memory; long term ID OBSESSIVE-COMPULSIVE DISORDER; ANXIETY DISORDERS; NEUROPSYCHOLOGICAL PERFORMANCE; COGNITIVE IMPAIRMENT; FRONTAL LOBES; DEFICITS; DEPRESSION; WITHDRAWAL; AMPHETAMINE; METABOLISM AB Background: Studies of the neurocognitive effects of long-term benzodiazepine use have been confounded by the presence of neurocognitive deficits characterizing the clinical conditions for which these medications are taken. Similarly, studies of the neurocognitive effects of anxiety disorders have been confounded by the inclusion of chronically benzodiazepine-medicated patients. This study was designed to tease apart the potentially confounding effects of long-term benzodiazepine use and panic disorder (PD) on memory and visuoconstructive abilities. Methods: Twenty chronically benzodiazepine-medicated and 20 benzodiazepine-free patients with PD with agoraphobia were compared with a group of 20 normal control participants, group-matched for age, education, and gender on a battery of neuropsychological tests assessing short-term, episodic long-term, and semantic memory, as well as visuoconstructive abilities. Results: Results indicated that benzodiazepine-free panic patients were relatively impaired in nonverbal short-term and nonverbal episodic long-term memory and visuoconstructive abilities, whereas verbal short-term and verbal episodic memory and semantic memory were preserved. Only limited evidence was found for more pronounced impairments in chronically benzodiazepine-medicated PD patients. Conclusions: This study provides evidence that patients with PD are characterized by relative impairments in nonverbal memory and visuoconstructive abilities, independent of benzodiazepine use. Nonetheless, we found evidence that chronic treatment with benzodiazepines is associated with intensification of select relative impairments in this realm. Documentation of these deficits raises questions about the broader etiology of neurocognitive impairment in PD as well as its impact on daily functioning. Depression and Anxiety 28: 999-1007, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Deckersbach, Thilo] Massachusetts Gen Hosp, Bipolar Clin, Dept Psychiat, Boston, MA 02114 USA. [Moshier, Samantha J.; Otto, Michael W.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Tuschen-Caffier, Brunna] Univ Freiburg, Freiburg, Germany. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Bipolar Clin, Dept Psychiat, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM tdeckersbach@partners.org FU DAAD (German Academic Exchange Service); NIMH [MH081116]; NARSAD; TSA; OCF; Organon (Merck); Medacorp; MGH Psychiatry Academy; BrainCells Inc.; Systems Research and Applications Corporation; Boston University; Catalan Agency for Health Technology Assessment and Research; National Association of Social Workers Massachusetts; Massachusetts Medical Society; Oxford University Press; NIH; NIA; Janssen Pharmaceuticals; Forest Research Institute; Shire Development Inc.; Medtronic; Cyberonics; Northstar; Pfizer FX Dr. Deckersbach was funded by a DAAD (German Academic Exchange Service) dissertation fellowship. Dr. Otto's effort on this project was supported in part by MH081116.; The authors disclose the following financial relationships within the past 3 years: Contract grant sponsor: NIMH; Contract grant number: MH081116; Contract grant sponsors: NIMH; NARSAD; TSA; OCF.; Disclosures: In the last 3 years, Dr. Otto has served as a consultant for Organon (Merck), has received royalties for use of the SIGH-A from Lilly, and received research support from Organon (Merck). Dr. Deckersbach has received honoraria, consultation fees and/or royalties from Medacorp, MGH Psychiatry Academy, BrainCells Inc., Systems Research and Applications Corporation, Boston University, the Catalan Agency for Health Technology Assessment and Research, the National Association of Social Workers Massachusetts, the Massachusetts Medical Society, and Oxford University Press. He has also participated in research funded by NIH, NIA, Janssen Pharmaceuticals, The Forest Research Institute, Shire Development Inc., Medtronic, Cyberonics, and Northstar. Dr. Tuschen-Caffier has received research support and honoraria from Pfizer. Samantha J. Moshier and Brunna Tuschen-Caffier have reported no conflict of interest. NR 67 TC 9 Z9 9 U1 1 U2 13 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 NOV PY 2011 VL 28 IS 11 BP 999 EP 1007 DI 10.1002/da.20891 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 850TH UT WOS:000297221800008 PM 22065537 ER PT J AU Gros, DF Antony, MM McCabe, RE Lydiard, RB AF Gros, Daniel F. Antony, Martin M. McCabe, Randi E. Lydiard, R. Bruce TI A PRELIMINARY INVESTIGATION OF THE EFFECTS OF COGNITIVE BEHAVIORAL THERAPY FOR PANIC DISORDER ON GASTROINTESTINAL DISTRESS IN PATIENTS WITH COMORBID PANIC DISORDER AND IRRITABLE BOWEL SYNDROME SO DEPRESSION AND ANXIETY LA English DT Article DE cognitive behavioral therapy; comorbidity; panic disorder; irritable bowel syndrome ID RANDOMIZED CONTROLLED-TRIAL; ANXIETY STRESS SCALES; DEPRESSION; SYMPTOMS; DYSREGULATION; FIBROMYALGIA; CYTOKINES; AXIS; INFLAMMATION; RELIABILITY AB Background: High comorbidity between panic disorder with/without agoraphobia (PD/A) and irritable bowel syndrome (IBS) has been identified in the literature. These findings have resulted in the recent development of neurobiological models to explain their overlapping symptoms and related origins. This study was a preliminary investigation of the influence of cognitive behavioral therapy (CBT) for PD/A on PD/A patients with and without comorbid IBS. Methods: All patients completed a thorough intake assessment, brief waitlist period, and a 12-week CBT group for PD/A. Results: The results demonstrated significant reductions in the symptoms of anxiety, depression, and overall impairment in both patient groups (ts > 2.3; Ps <.05). In addition, PD/A patients with comorbid IBS also experienced reductions in the disability and distress associated with their gastrointestinal symptoms of IBS (ts > 1.9; Ps <.07). Conclusions: Although additional research still is needed, these preliminary findings suggest that CBT for PD/A can be used to simultaneously treat comorbid symptoms of PD/A and IBS. Implications for the neurobiological models for these comorbid conditions were discussed. Depression and Anxiety 28: 1027-1033, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Gros, Daniel F.; Lydiard, R. Bruce] Ralph H Johnson VAMC, Mental Hlth Serv, Charleston, SC USA. [Gros, Daniel F.; Lydiard, R. Bruce] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Antony, Martin M.] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. [Antony, Martin M.; McCabe, Randi E.] St Josephs Healthcare, Anxiety Treatment & Res Ctr, Hamilton, ON, Canada. [McCabe, Randi E.] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu RI Antony, Martin/K-1991-2012 OI Antony, Martin/0000-0002-3508-377X FU Ralph H. Johnson VAMC FX This material is the result of work supported with resources and the use of facilities at the Ralph H. Johnson VAMC. 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 United States government. NR 45 TC 2 Z9 2 U1 3 U2 6 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 NOV PY 2011 VL 28 IS 11 BP 1027 EP 1033 DI 10.1002/da.20863 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 850TH UT WOS:000297221800011 PM 21770001 ER PT J AU Patwardhan, V Paul, S Corey, KE Mazhar, SM Richter, JM Thiim, M Chung, RT AF Patwardhan, Vilas Paul, Sonali Corey, Kathleen E. Mazhar, Sameer M. Richter, James M. Thiim, Michael Chung, Raymond T. TI Hepatocellular Carcinoma Screening Rates Vary by Etiology of Cirrhosis and Involvement of Gastrointestinal Sub-specialists SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Cirrhosis; Hepatocellular carcinoma; Screening; Non-alcoholic steatohepatitis ID UNITED-STATES; BARIATRIC SURGERY; LIVER-DISEASE; RISK-FACTORS; HEPATITIS-C; CANCER; SURVEILLANCE; MANAGEMENT; SURVIVAL; OUTCOMES AB Background Regular screening of cirrhotic patients for hepatocellular carcinoma (HCC) has been suboptimal, but there is little data regarding specific risk factors for reduced screening. Methods From 1996 to 2010, patients with cirrhosis were retrospectively identified from outpatient gastroenterology and primary care practices. Data was obtained from the diagnosis of cirrhosis until the time of elevated alpha-fetoprotein (AFP) or lesion suspicious for HCC, death, liver transplantation, or end of the data collection period. Recommended screening was defined as abdominal imaging (ultrasound, contrast-enhanced CT, or MRI) with or without serum alpha-fetoprotein (AFP) at least once every 12 months based on professional guidelines. Results One hundred fifty-six patients with cirrhosis were identified. The etiologies of cirrhosis were viral hepatitis (n = 65), alcohol (n = 40), non-alcoholic steatohepatitis (NASH) (n = 27), and non-viral, non-alcoholic, non-NASH cirrhosis (n = 24). Of the 156 patients, 51% received recommended screening for HCC. Patients with NASH cirrhosis received recommended screening significantly less (p = 0.016) than cirrhotics with viral hepatitis, alcoholic cirrhosis, or non-viral, non-alcoholic, non-NASH cirrhosis and were less likely to receive gastroenterology referral (p < 0.001). Additionally, 20 patients were diagnosed with cirrhosis incidentally during a surgical procedure. These patients were significantly less likely to receive recommended HCC screening than those diagnosed non-surgically (10.0 vs. 56.6%; p < 0.001). Screening was significantly more likely to occur in patients seen regularly by a gastrointestinal subspecialist (66.7 vs. 22.8%; p < 0.001). Conclusions Patients with NASH cirrhosis and incidentally discovered cirrhosis have low rates of HCC screening and are referred less often to gastroenterologists. These data suggest a need for increased education about NASH cirrhosis and better systems of communication among general practitioners, surgeons, and gastroenterologists. C1 [Patwardhan, Vilas; Paul, Sonali; Corey, Kathleen E.; Mazhar, Sameer M.; Richter, James M.; Thiim, Michael; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Corey, Kathleen E.; Mazhar, Sameer M.; Richter, James M.; Thiim, Michael; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Warren 1007,55 Fruit St, Boston, MA 02114 USA. EM vpatwardhan@partners.org; spaul1@partners.org; kcorey@partners.org; smazhar@partners.org; jrichter@partners.org; mthiim@partners.org; rtchung@partners.org FU NIH [DK078772] FX We thank Dr. Kathleen Finn and Dr. Daniel Hunt for their critical reading of this manuscript and their suggestions. Part of this work was presented at a poster session at the 61st Annual Meeting of the American Association for the Study of Liver Diseases; 2010 November 2; Boston, MA. Raymond T. Chung was supported by NIH DK078772. NR 26 TC 9 Z9 9 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD NOV PY 2011 VL 56 IS 11 BP 3316 EP 3322 DI 10.1007/s10620-011-1836-2 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 843AE UT WOS:000296643400029 PM 21805170 ER PT J AU Kesari, S Advani, SJ Lawson, JD Kahle, KT Ng, K Carter, B Chen, CC AF Kesari, Santosh Advani, Sunil J. Lawson, Joshua D. Kahle, Kristopher T. Ng, Kimberly Carter, Bob Chen, Clark C. TI DNA damage response and repair: insights into strategies for radiation sensitization of gliomas SO FUTURE ONCOLOGY LA English DT Review DE chemotherapy; DNA damage response; DNA double strand break repair; glioblastoma; radiosensitization; radiotherapy ID DOUBLE-STRAND BREAK; DIAGNOSED GLIOBLASTOMA-MULTIFORME; IN-VIVO RADIOSENSITIZATION; SUSCEPTIBILITY GENE BRCA2; DEPENDENT PROTEIN-KINASE; END-JOINING PATHWAYS; MAMMALIAN-CELLS; CANCER-CELLS; HOMOLOGOUS RECOMBINATION; ADJUVANT TEMOZOLOMIDE AB The incorporation of radiotherapy into multimodality treatment plans has led to significant improvements in glioma patient survival. However, local recurrence from glioma resistance to ionizing radiation remains a therapeutic challenge. The tumoricidal effect of radiation therapy is largely attributed to the induction of dsDNA breaks (DSBs). In the past decade, there have been tremendous strides in understanding the molecular mechanisms underlying DSB repair. The identification of gene products required for DSB repair has provided novel therapeutic targets. Recent studies revealed that many US FDA-approved cancer agents inhibit DSB repair by interacting with repair proteins. This article will aim to provide discussion of DSB repair mechanisms to provide molecular targets for radiation sensitization of gliomas and a discussion of FDA-approved cancer therapies that modulate DSB repair to highlight opportunities for combination therapy with radiotherapy for glioma therapy. C1 [Chen, Clark C.] Univ Calif San Diego, Div Neurosurg, Moores Canc Ctr, Ctr Theoret & Appl Neurooncol, La Jolla, CA 92093 USA. [Kesari, Santosh] Univ Calif San Diego, Moores UCSD Canc Ctr, Dept Neurosci, La Jolla, CA 92093 USA. [Advani, Sunil J.; Lawson, Joshua D.] Univ Calif San Diego, Moores Canc Ctr, Dept Radiat Oncol, La Jolla, CA 92093 USA. [Kahle, Kristopher T.] Harvard Univ, Sch Med, Boston, MA USA. [Kahle, Kristopher T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Ng, Kimberly; Chen, Clark C.] Dana Farber Canc Inst, Div Genom Stabil & DNA Repair, Dept Radiat Oncol, Boston, MA 02115 USA. RP Chen, CC (reprint author), Univ Calif San Diego, Div Neurosurg, Moores Canc Ctr, Ctr Theoret & Appl Neurooncol, 3855 Hlth Sci Dr 0987, La Jolla, CA 92093 USA. EM clarkchen@ucsd.edu RI Kesari, Santosh/E-8461-2013 FU Doris Duke Charitable Foundation; Sontag Foundation; Burroughs Wellcome Fund Career Awards for Medical Sciences; Kimmel Scholar award; American Brain Tumor Association; National Cancer Institute; NIH [K08CA124804, ARRA 3P30CA023100-25S8]; James S McDonnell Foundation FX CC Chen is supported by the Doris Duke Charitable Foundation Clinical Scientist Development Award, the Sontag Foundation Distinguished Scientist Award, the Burroughs Wellcome Fund Career Awards for Medical Sciences, the Kimmel Scholar award, a Discovery Grant from the American Brain Tumor Association, and a National Cancer Institute K12 award. This work was supported in part by grants from NIH K08CA124804, ARRA 3P30CA023100-25S8 and a James S McDonnell Foundation award to S Kesari. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 104 TC 14 Z9 17 U1 1 U2 7 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 J9 FUTURE ONCOL JI Future Oncol. PD NOV PY 2011 VL 7 IS 11 BP 1335 EP 1346 DI 10.2217/FON.11.111 PG 12 WC Oncology SC Oncology GA 850SQ UT WOS:000297219300014 PM 22044206 ER PT J AU Huang, ES Karsan, S Kanwal, F Singh, I Makhani, M Spiegel, BM AF Huang, Edward S. Karsan, Sundip Kanwal, Fasiha Singh, Inder Makhani, Marc Spiegel, Brennan M. TI Impact of nasogastric lavage on outcomes in acute GI bleeding SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID UPPER GASTROINTESTINAL HEMORRHAGE; RANDOMIZED CONTROLLED-TRIAL; NATIONAL ASGE SURVEY; LENGTH-OF-STAY; CONSENSUS RECOMMENDATIONS; TRACT HEMORRHAGE; EARLY ENDOSCOPY; MANAGEMENT; PREDICTORS; GUIDELINE AB Background: Nasogastric lavage (NGL) is often performed early in the management of GI bleeding. This practice assumes that NGL results can assist with timely risk stratification and management. Objective: We performed a retrospective analysis to test whether NGL is associated with improved process measures and outcomes in GI bleeding. Design: Propensity-matched retrospective analysis. Setting: University-based Veterans Affairs medical center. Patients: A total of 632 patients admitted with GI bleeding. Main Outcome Measurements: Thirty-day mortality rate, length of hospital stay, transfusion requirements, surgery, and time to endoscopy. Results: Patients receiving NGL were more likely to take nonsteroidal anti-inflammatory drugs and be admitted to intensive care, but less likely to have metastatic disease or tachycardia, be taking warfarin, or present on weekdays. After propensity matching, NGL did not affect mortality (odds ratio [OR] 0.84; 95% confidence interval [CI], 0.37-1.92), length of hospital stay (7.3 vs 8.1 days, P = .57), surgery (OR 1.51; 95% CI, 0.42-5.43), or transfusions (3.2 vs 3.0 units, P = .94). However, NGL was associated with earlier time to endoscopy (hazard ratio 1.49; 95% CI, 1.09-2.04), and bloody aspirates were associated high-risk lesions (OR 2.69; 95% CI, 1.08-6.73). Limitations: Retrospective design. Conclusions: Performing NGL is associated with the earlier performance of endoscopy, but does not affect clinical outcomes. Performing NGL at initial triage may promote more timely process of care, but further studies will be needed to confirm these findings. (Gastrointest Endosc 2011; 74: 971-80.) C1 [Huang, Edward S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Karsan, Sundip; Makhani, Marc] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Karsan, Sundip; Makhani, Marc] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Spiegel, Brennan M.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Los Angeles, CA USA. [Kanwal, Fasiha] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. [Singh, Inder; Spiegel, Brennan M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Kanwal, Fasiha; Spiegel, Brennan M.] UCLA VA Ctr Outcomes Res & Educ, Los Angeles, CA USA. RP Spiegel, BM (reprint author), 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU American Gastroenterological Association FX The authors disclosed no financial relationships relevant to this publication. Dr. Huang is supported by American Gastroenterological Association Fellowship to Faculty Transition Award. There was no external funding for this study. The opinions and assertions contained herein are the sole views of the authors and are not to be construed as official or as reflecting the views of the Department of Veteran Affairs. NR 31 TC 23 Z9 24 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV PY 2011 VL 74 IS 5 BP 971 EP 980 DI 10.1016/j.gie.2011.04.045 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 845ZP UT WOS:000296867300006 PM 21737077 ER PT J AU Yoo, H Kang, D Katz, AJ Lauwers, GY Nishioka, NS Yagi, Y Tanpowpong, P Namati, J Bouma, BE Tearney, GJ AF Yoo, Hongki Kang, DongKyun Katz, Aubrey J. Lauwers, Gregory Y. Nishioka, Norman S. Yagi, Yukako Tanpowpong, Pornthep Namati, Jacqueline Bouma, Brett E. Tearney, Guillermo J. TI Reflectance confocal microscopy for the diagnosis of eosinophilic esophagitis: a pilot study conducted on biopsy specimens SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID ORAL VISCOUS BUDESONIDE; LIGHT-SCATTERING; BARRETTS-ESOPHAGUS; FLUTICASONE PROPIONATE; LASER ENDOMICROSCOPY; CERVICAL CELLS; ACETIC-ACID; CHILDREN; ADULTS; ENDOSCOPY AB Background: Diagnosis of eosinophilic esophagitis (EoE) currently requires endoscopic biopsy and histopathologic analysis of the biopsy specimens to count intraepithelial eosinophils. Reflectance confocal microscopy (RCM) is an endomicroscopy technology that is capable of obtaining high-resolution, optically sectioned images of esophageal mucosa without the administration of exogenous contrast. Objective: In this study, we investigated the capability of a high-speed form of RCM, termed spectrally encoded confocal microscopy (SECM), to count intraepithelial esophageal eosinophils and characterize other microscopic findings of EoE. Design: A total of 43 biopsy samples from 35 pediatric patients and 8 biopsy samples from 8 adult patients undergoing EGD for EoE were imaged by SECM immediately after their removal and then processed for routine histopathology. Two SECM readers, trained on adult cases, prospectively counted intraepithelial eosinophils and detected the presence of abscess, degranulation, and basal cell hyperplasia on SECM images from the pediatric patients. A pathologist blinded to the SECM data analyzed the same from corresponding slides. Setting: The Gastrointestinal Unit, Massachusetts General Hospital. Results: Eosinophils by SECM demonstrated a higher reflectance than the surrounding cells and other inflammatory cells. There was good correlation between SECM and histology maximum eosinophil counts/high-power field (R = 0.76, P < .0001). Intra-and interobserver correlations for SECM counts were very good (R = 0.93 and R = 0.92, respectively; P < .0001). For the commonly used eosinophil count cutoff of 15 per high-power field, the sensitivity and specificity of SECM for EoE were 100%. The sensitivity and specificity for abscess, degranulation, and basal cell hyperplasia were 100% and 82%, 91% and 60%, and 94% and 80%, respectively. Intra-and interobserver agreements for these microscopic features of EoE were very good (kappa = 0.9/0.9, 0.84/1.0, 0.91/0.81, respectively). Limitation: Ex vivo study. Conclusions: This study demonstrates that RCM can be used to accurately count intraepithelial eosinophils and identify other microscopic abnormalities associated with EoE on freshly excised biopsy samples. These findings suggest that RCM may be developed into a tool for assessing eosinophilic infiltration in the esophagus in vivo. (Gastrointest Endosc 2011;74:992-1000.) C1 [Yoo, Hongki; Kang, DongKyun; Namati, Jacqueline; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Yoo, Hongki; Kang, DongKyun; Namati, Jacqueline; Tearney, Guillermo J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Lauwers, Gregory Y.; Yagi, Yukako] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Katz, Aubrey J.; Nishioka, Norman S.; Tanpowpong, Pornthep] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Katz, Aubrey J.; Tanpowpong, Pornthep] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Food Allergy Ctr, Boston, MA 02114 USA. [Bouma, Brett E.; Tearney, Guillermo J.] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. RP Tearney, GJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Parkman St,RSH 160A, Boston, MA 02114 USA. RI Yoo, Hongki/B-6421-2013; Kang, Dongkyun/C-1085-2013 OI Yoo, Hongki/0000-0001-9819-3135; Kang, Dongkyun/0000-0001-5063-5387 FU Ninepoint Medical Inc.; National Institutes of Health [R21CA122161, R01DK091923] FX The following authors disclosed a financial relationship relevant to this publication: Drs Tearney and Bouma consult for and receive nonclinical sponsored research from Ninepoint Medical Inc. Ninepoint Medical Inc. has a technology-licensing agreement with Massachusetts General Hospital. Some authors (G.J.T., B.E.B., H.Y., D.K.) have rights to receive royalties as a result of this licensing arrangement. Dr. Namati works as a consultant for and has equity interest in Ninepoint Medical Inc. The other authors disclosed no financial relationships relevant to this publication. This research was supported in part by National Institutes of Health (grant numbers R21CA122161 and R01DK091923). NR 59 TC 12 Z9 13 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV PY 2011 VL 74 IS 5 BP 992 EP 1000 DI 10.1016/j.gie.2011.07.020 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 845ZP UT WOS:000296867300009 PM 21944314 ER PT J AU van Duin, M Broyl, A de Knegt, Y Goldschmidt, H Richardson, PG Hop, WCJ van der Holt, B Joseph-Pietras, D Mulligan, G Neuwirth, R Sahota, SS Sonneveld, P AF van Duin, Mark Broyl, Annemiek de Knegt, Yvonne Goldschmidt, Hartmut Richardson, Paul G. Hop, Wim C. J. van der Holt, Bronno Joseph-Pietras, Debora Mulligan, George Neuwirth, Rachel Sahota, Surinder S. Sonneveld, Pieter TI Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE multiple myeloma; relapse; testis antigen expression; prognosis; immunotherapy ID KINASE-INTERACTING PROTEIN; GENE-EXPRESSION; MOLECULAR CLASSIFICATION; STRUCTURAL HOMOLOGY; DNA VACCINES; STEM-CELLS; T-CELLS; BORTEZOMIB; PROLIFERATION; MAGE-C1/CT7 AB Background In multiple myeloma, expression of cancer testis antigens may provide prognostic markers and potential targets for immunotherapy. Expression at relapse has not yet been evaluated for a large panel of cancer testis antigens which can be classified by varying expression in normal tissue: restricted to testis, expressed in testis and brain and not restricted but selectively expressed in testis. Design and Methods Evaluation of cancer testis antigen expression was made in newly diagnosed multiple myeloma cases (HOVON-65/GMMG-HD4 trial; n=320) and in relapse cases (APEX, SUMMIT, CREST trials; n=264). Presence of expression using Affymetrix GeneChips was determined for 123 cancer testis antigens. Of these 87 had a frequency of more than 5% in the newly diagnosed and relapsed patients, and were evaluated in detail. Results Tissue restriction was known for 58 out of 87 cancer testis antigens. A significantly lower frequency of presence calls in the relapsed compared to newly diagnosed cases was found for 3 out of 13 testis restricted genes, 2 out of 7 testis/brain restricted genes, and 17 out of 38 testis selective genes. MAGEC1, MAGEB2 and SSX1 were the most frequent testis-restricted cancer testis antigens in both data sets. Multivariate analysis demonstrated that presence of MAGEA6 and CDCA1 were clearly associated with shorter progression free survival, and presence of MAGEA9 with shorter overall survival in the set of newly diagnosed cases. In the set of relapse cases, presence of CTAG2 was associated with shorter progression free survival and presence of SSX1 with shorter overall survival. Conclusions Relapsed multiple myeloma reveals extensive cancer testis antigen expression. Cancer testis antigens are confirmed as useful prognostic markers in newly diagnosed multiple myeloma patients and in relapsed multiple myeloma patients. C1 [van Duin, Mark; Broyl, Annemiek; de Knegt, Yvonne; Sonneveld, Pieter] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Goldschmidt, Hartmut] Univ Heidelberg, Dept Internal Med, Div Hematol Oncol, Sect Multiple Myeloma, D-6900 Heidelberg, Germany. [Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [van Duin, Mark; Hop, Wim C. J.] Erasmus MC, Dept Biostat, NL-3015 GE Rotterdam, Netherlands. [van der Holt, Bronno] Erasmus MC Daniel den Hoed, HOVON Data Ctr, Rotterdam, Netherlands. [Joseph-Pietras, Debora; Sahota, Surinder S.] Univ Southampton, Sch Med, Canc Sci Div, Southampton SO9 5NH, Hants, England. [Mulligan, George; Neuwirth, Rachel] Millennium Pharmaceut Inc, Cambridge, MA USA. RP van Duin, M (reprint author), Erasmus MC, Dept Biostat, Ee1391B,Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands. EM m.vanduin@erasmusmc.nl FU Leukemia Research Foundation (UK); Myeloma Stem Cell Network (MSCNET) FX this study was funded by Leukemia Research Foundation (UK) and the Myeloma Stem Cell Network (MSCNET/FP6). NR 51 TC 27 Z9 27 U1 0 U2 4 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2011 VL 96 IS 11 BP 1662 EP 1669 DI 10.3324/haematol.2010.037978 PG 8 WC Hematology SC Hematology GA 851BR UT WOS:000297243800016 PM 21791470 ER PT J AU Jalovec, K Swick, S Becker, C Reifsnyder, R AF Jalovec, Kathryn Swick, Susan Becker, Corky Reifsnyder, Robert TI When the Lightning Rod Leaves Home: A Family Therapy Case Characterized by Successive Generations of Familial Conflict During a Transition into Young Adulthood SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE eating disorder; family therapy; young adulthood ID ANOREXIA-NERVOSA; PARENTAL CANCER; BULIMIA-NERVOSA; ADOLESCENTS; CHILDREN; IMPACT C1 [Jalovec, Kathryn; Swick, Susan; Reifsnyder, Robert] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Jalovec, Kathryn; Swick, Susan; Reifsnyder, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Becker, Corky] Cambridge Hosp, Cambridge, MA 02139 USA. RP Jalovec, K (reprint author), 4535 Harding Rd,Suite 102, Nashville, TN 37205 USA. EM kathryncody@gmail.com NR 22 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 NOV-DEC PY 2011 VL 19 IS 6 BP 302 EP 312 DI 10.3109/10673229.2011.632600 PG 11 WC Psychiatry SC Psychiatry GA 850BT UT WOS:000297170100003 PM 22098326 ER PT J AU Chang, MC DeCaro, JJ Zheng, M Gearing, M Shubeck, L Sherman, SL Welt, CK AF Chang, Martin C. DeCaro, John J. Zheng, Mei Gearing, Marla Shubeck, Lisa Sherman, Stephanie L. Welt, Corrine K. TI Ovarian histopathological and ubiquitin-immunophenotypic features in fragile X-associated primary ovarian insufficiency: a study of five cases and selected controls SO HISTOPATHOLOGY LA English DT Letter ID PREMUTATION CARRIERS; CGG REPEAT; EXPANSION; RNA C1 [Chang, Martin C.] Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada. [DeCaro, John J.; Sherman, Stephanie L.] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. [Zheng, Mei] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gearing, Marla; Shubeck, Lisa] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Welt, Corrine K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chang, MC (reprint author), Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada. RI Chang, Martin/J-2329-2016; OI Welt, Corrine/0000-0002-8219-5504 FU NICHD NIH HHS [R01 HD029909-14, R01 HD029909, R01 HD29909] NR 11 TC 3 Z9 4 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD NOV PY 2011 VL 59 IS 5 BP 1018 EP 1023 DI 10.1111/j.1365-2559.2011.03959.x PG 6 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 851CC UT WOS:000297244900029 PM 22007616 ER PT J AU Pal, J Sanal, MG Gopal, GJ AF Pal, Jagannath Sanal, Madhusudana Girija Gopal, Gopal Jee TI Vitamin-C as anti-Helicobacter pylori agent: More prophylactic than curative- Critical review SO INDIAN JOURNAL OF PHARMACOLOGY LA English DT Review DE Helicobacter pylori; prophylactic; supplementation; urease; vitamin C ID PROTON PUMP INHIBITORS; ASCORBIC-ACID; GASTRIC-JUICE; ERADICATION RATE; TRIPLE THERAPY; HUMAN STOMACH; INFECTION; UREASE; SUPPLEMENTATION; NITROIMIDAZOLES AB Potential of nonantibiotic therapies for treatment of Helicobacter pylori-related acid peptic disease remains underexplored. Several clinical studies have shown that higher prevalence of H. pylori infection is associated with low Vitamin C (Vit C) level in serum and gastric juice. However, there is no consensus regarding the usefulness of Vit C supplementation in the management of H. pylori infection. Surveying the existing literature we conclude that high concentration of Vit C in gastric juice might inactivate H. pylori urease, the key enzyme for the pathogen's survival and colonization into acidic stomach. Once infection established, urease is not very important for its survival. The role of Vit-C as anti-H. pylori agent in peptic ulcer diseases appears to be preventive rather than curative. Rather than supplementing high dose of Vit C along with conventional triple therapy, it is preferable to complete the conventional therapy and thereafter start Vit C supplementation for extended period which would prevent reinfection in susceptible individuals, provided the patients are not achlorhydric. Further studies are required to prove the role of Vit C in susceptible population. C1 [Pal, Jagannath] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sanal, Madhusudana Girija] Inst Liver & Biliary Sci, Dept Res, New Delhi 110070, India. [Gopal, Gopal Jee] Jawaharlal Nehru Univ, Special Ctr Mol Med, New Delhi 110067, India. RP Pal, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM jagannath_pal@dfci.harvard.edu NR 45 TC 3 Z9 3 U1 1 U2 4 PU MEDKNOW PUBLICATIONS PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0019-5472 J9 INDIAN J PHARMACOL JI Indian J. Pharmacol. PD NOV-DEC PY 2011 VL 43 IS 6 BP 624 EP 627 DI 10.4103/0253-7613.89814 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 850UL UT WOS:000297224900002 PM 22144762 ER PT J AU Rosenblatt, LE Gorantla, S Torres, JA Yarmush, RS Rao, S Park, ER Denninger, JW Benson, H Fricchione, GL Bernstein, B Levine, JB AF Rosenblatt, Lucy E. Gorantla, Sasikanth Torres, Jodi A. Yarmush, Rubin S. Rao, Surita Park, Elyse R. Denninger, John W. Benson, Herbert Fricchione, Gregory L. Bernstein, Bruce Levine, John B. TI Relaxation Response-Based Yoga Improves Functioning in Young Children with Autism: A Pilot Study SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID ABERRANT BEHAVIOR CHECKLIST; PERVASIVE DEVELOPMENTAL DISORDERS; BRAIN GABA LEVELS; SPECTRUM DISORDERS; ATYPICAL ANTIPSYCHOTICS; ASSESSMENT SYSTEM; ADOLESCENTS; VALIDITY; COMPLEMENTARY; INTERVENTION AB Objectives: The study objectives were to develop and objectively assess the therapeutic effect of a novel movement-based complementary and alternative medicine approach for children with an autism-spectrum disorder (ASD). Design: A within-subject analysis comparing pre- to post-treatment scores on two standard measures of childhood behavioral problems was used. Settings and location: The intervention and data analysis occurred at a tertiary care, medical school teaching hospital. Subjects: Twenty-four (24) children aged 3-16 years with a diagnosis of an ASD comprised the study group. Intervention: The efficacy of an 8-week multimodal yoga, dance, and music therapy program based on the relaxation response (RR) was developed and examined. Outcome measures: The study outcome was measured using The Behavioral Assessment System for Children, Second Edition (BASC-2) and the Aberrant Behavioral Checklist (ABC). Results: Robust changes were found on the BASC-2, primarily for 5-12-year-old children. Unexpectedly, the post-treatment scores on the Atypicality scale of the BASC-2, which measures some of the core features of autism, changed significantly (p = 0.003). Conclusions: A movement-based, modified RR program, involving yoga and dance, showed efficacy in treating behavioral and some core features of autism, particularly for latency-age children. C1 [Yarmush, Rubin S.; Denninger, John W.; Benson, Herbert; Fricchione, Gregory L.; Levine, John B.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Rosenblatt, Lucy E.; Gorantla, Sasikanth; Torres, Jodi A.; Yarmush, Rubin S.; Rao, Surita; Bernstein, Bruce; Levine, John B.] St Francis Hosp & Med Ctr, Dept Psychiat, Hartford, CT USA. [Gorantla, Sasikanth; Park, Elyse R.] Univ Hartford, Dept Psychiat, Hartford, CT USA. [Rao, Surita; Bernstein, Bruce] Univ Connecticut, Dept Psychiat, Farmington, CT 06107 USA. [Park, Elyse R.; Denninger, John W.; Benson, Herbert; Fricchione, Gregory L.; Levine, John B.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Levine, JB (reprint author), Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, 151 Merrimac St,4th Floor, Boston, MA 02114 USA. EM jblevine@partners.org RI Levine, John/G-6221-2015 FU Centers for Disease Control and Prevention [5R01DP000339]; Department of Innovation and Quality Integration, Saint Francis Hospital and Medical Center FX This investigation was supported by funds from the Centers for Disease Control and Prevention, Grant number 5R01DP000339, and a grant from the Department of Innovation and Quality Integration, Saint Francis Hospital and Medical Center. NR 39 TC 13 Z9 15 U1 4 U2 47 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD NOV PY 2011 VL 17 IS 11 BP 1029 EP 1035 DI 10.1089/acm.2010.0834 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 850SA UT WOS:000297217000010 PM 21992466 ER PT J AU Sidhu, MS Venkatesh, V Hoffmann, U Ghoshhajra, BB AF Sidhu, Manavjot S. Venkatesh, Vikram Hoffmann, Udo Ghoshhajra, Brian B. TI Advanced Adaptive Axial-Sequential Prospectively Electrocardiogram-Triggered Dual-Source Coronary Computed Tomographic Angiography in a Patient With Atrial Fibrillation SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE atrial fibrillation; dual-source coronary CT angiography ID ARTERY-DISEASE AB Atrial fibrillation is considered a relative contraindication to coronary computed tomographic angiography (CCTA) because image quality and radiation dose-saving measures largely depend on low and stable heart rates. Most published experiences with CCTA during atrial fibrillation have relied on retrospective gating to mitigate artifacts via electrocardiogram editing. However, a large number of patients arrive at the CT suite with irregular heart rates. We present a case in which we used a prospectively electrocardiogram-triggered axial-sequential scan mode with a novel arrhythmia protection algorithm to obtain motion-free, high-quality CCTA images at a low radiation dose. C1 [Sidhu, Manavjot S.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Dept Cardiovasc Imaging, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Sidhu, Manavjot S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sidhu, MS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Dept Cardiovasc Imaging, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM msidhu1@partners.org NR 4 TC 5 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV-DEC PY 2011 VL 35 IS 6 BP 747 EP 748 DI 10.1097/RCT.0b013e3182355960 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849GJ UT WOS:000297113300015 PM 22082547 ER PT J AU Smart, RJ Marsh, S Rosenberg, M AF Smart, Ryan J. Marsh, Shawn Rosenberg, Morton TI Intraosseous Access in Oral and Maxillofacial Surgical Practice SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID CARDIOPULMONARY-RESUSCITATION; INFUSION DEVICES; HUMERUS; ADULTS C1 [Smart, Ryan J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Marsh, Shawn; Rosenberg, Morton] Tufts Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02111 USA. [Rosenberg, Morton] Tufts Univ, Sch Dent Med, Div Anesthesia & Pain Control, Boston, MA 02111 USA. [Rosenberg, Morton] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Smart, RJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM rjsmart@partners.org NR 23 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 2011 VL 69 IS 11 BP 2708 EP 2713 DI 10.1016/j.joms.2011.02.101 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 849PQ UT WOS:000297138000007 PM 21757277 ER PT J AU Susarla, SM Abramson, ZR Dodson, TB Kaban, LB AF Susarla, Srinivas M. Abramson, Zachary R. Dodson, Thomas B. Kaban, Leonard B. TI Upper Airway Length Decreases After Maxillomandibular Advancement in Patients With Obstructive Sleep Apnea SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID COMPUTED TOMOGRAPHIC ANALYSIS; SURGERY; ANATOMY AB Purpose: Most reports on airway anatomy after maxillomandibular advancement (MMA) for obstructive sleep apnea (OSA) have focused on changes in airway diameter, ie, posterior airway space (PAS), rather than airway length. The purpose of this study was to evaluate changes in cephalometrically measured upper airway length (UAL) after MMA. Materials and Methods: This was a retrospective cohort study. The sample was composed of subjects who underwent MMA for OSA. The primary outcome measurement was change in UAL measured on lateral cephalograms. Predictor variables included patient demographic and cephalometric characteristics. Secondary outcome measurements were changes in sleep disturbance. Descriptive, bivariate, and regression statistics were computed. For all analyses, P <= .05 was considered statistically significant. Results: The sample included 23 adult subjects (mean age, 39.3 +/- 12.1 years; 6 women). Subjects had average maxillary and mandibular advancements of 9.8 +/- 2.0 and 10.8 +/- 2.2 mm, respectively. Mean pre- and postoperative UALs were 75.8 +/- 7.0 and 67.0 +/- 5.7 mm, respectively (P <.001). Mean pre- and postoperative respiratory disturbance indexes were 53.2 +/- 22.4 and 19.0 +/- 12.0 events/hour, respectively (P = .003). All patients had improvement in OSA symptoms, but 3 (13%) required continuous positive airway pressure. Conclusion: The results of this study suggest that UAL decreases as a result of MMA. In addition, these results support the observation that MMA is associated with objective and subjective improvements in patients with OSA. (C) 2011 American Association of Oral and Maxillofacial Surgeons j Oral Maxi llofac Surg 69:2872-2878, 2011 C1 [Susarla, Srinivas M.; Abramson, Zachary R.; Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Dodson, Thomas B.] Massachusetts Gen Hosp, Ctr Appl Clin Invest, Boston, MA 02114 USA. [Dodson, Thomas B.; Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Susarla, SM (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, WACC230, Boston, MA 02114 USA. EM ssusarla1@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU Oral and Maxillofacial Surgery Foundation; AO/Synthes Research Fellowship in Pediatric Maxillofacial Surgery; Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research; Center for Applied Clinical Investigation; Massachusetts General Physicians Organization FX This study was completed with support from the Oral and Maxillofacial Surgery Foundation Fellowship in Clinical Investigation (S.M.S.), the AO/Synthes Research Fellowship in Pediatric Maxillofacial Surgery (Z.R.A.), the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund (S.M.S., Z.R.A.) and the Center for Applied Clinical Investigation (T.B.D., S.M.S.), and the Massachusetts General Physicians Organization (T.B.D., NR 15 TC 16 Z9 17 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 NOV PY 2011 VL 69 IS 11 BP 2872 EP 2878 DI 10.1016/j.joms.2011.01.005 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 849PQ UT WOS:000297138000034 PM 21507540 ER PT J AU Shin, JM Inatomi, N Munson, K Strugatsky, D Tokhtaeva, E Vagin, O Sachs, G AF Shin, Jai Moo Inatomi, Nobuhiro Munson, Keith Strugatsky, David Tokhtaeva, Elmira Vagin, Olga Sachs, George TI Characterization of a Novel Potassium-Competitive Acid Blocker of the Gastric H,K-ATPase, 1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylm ethanamine Monofumarate (TAK-438) SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; PROTON PUMP INHIBITOR; BINDING-SITES; ESOMEPRAZOLE; H+,K+-ATPASE; ATPASE; LANSOPRAZOLE; SECRETION; MEMBRANES; VESICLES AB Inhibition of the gastric H, K-ATPase by the potassium-competitive acid blocker (P-CAB) 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine (TAK-438), is strictly K(+)-competitive with a K(i) of 10 nM at pH 7. In contrast to previous P-CABs, this structure has a point positive charge (pK(a) 9.06) allowing for greater accumulation in parietal cells compared with previous P-CABs [e.g., (8-benzyloxy-2-methyl-imidazo(1,2-a)pyridin-3-yl)acetonitrile (SCH28080), pK(a) 5.6]. The dissociation rate of the compound from the isolated ATPase is slower than other P-CABs, with the t(1/2) being 7.5 h in 20 mM KCl at pH 7. The stoichiometry of binding of TAK-438 to the H,K-ATPase is 2.2 nmol/mg in the presence of Mg-ATP, vanadate, or MgP(i). However, TAK-438 also binds enzyme at 1.3 nmol/mg in the absence of Mg(2+). Modeling of the H, K-ATPase to the homologous Na,K-ATPase predicts a close approach and hydrogen bonding between the positively charged N-methylamino group and the negatively charged Glu795 in the K(+)-binding site in contrast to the planar diffuse positive charge of previous P-CABs. This probably accounts for the slow dissociation and high affinity. The model also predicts hydrogen bonding between the hydroxyl of Tyr799 and the oxygens of the sulfonyl group of TAK-438. A Tyr799Phe mutation resulted in a 3-fold increase of the dissociation rate, showing that this hydrogen bonding also contributes to the slow dissociation rate. Hence, this K(+)-competitive inhibitor of the gastric H,K-ATPase should provide longer-lasting inhibition of gastric acid secretion compared with previous drugs of this class. C1 [Shin, Jai Moo] VA Greater Los Angeles Healthcare Syst, Membrane Biol Lab, Los Angeles, CA 90073 USA. [Shin, Jai Moo; Munson, Keith; Strugatsky, David; Tokhtaeva, Elmira; Vagin, Olga; Sachs, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol & Med, Los Angeles, CA 90024 USA. [Inatomi, Nobuhiro] Takeda Pharmaceut Co Ltd, Div Pharmaceut Res, Osaka, Japan. RP Shin, JM (reprint author), VA Greater Los Angeles Healthcare Syst, Membrane Biol Lab, 11301 Wilshire Blvd,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. EM jaishin@ucla.edu FU Takeda Pharmaceutical Company Limited; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [DK053642, DK058333, DK077149]; U.S. VA Merit Grant Award [I01BX001006-01] FX This work was supported by Takeda Pharmaceutical Company Limited; the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grants DK053642, DK058333, DK077149]; and a U.S. VA Merit Grant Award [I01BX001006-01]. NR 30 TC 40 Z9 42 U1 0 U2 10 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2011 VL 339 IS 2 BP 412 EP 420 DI 10.1124/jpet.111.185314 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 840TS UT WOS:000296464800011 PM 21828261 ER PT J AU Wang, JH Inoue, T Higashiyama, M Guth, PH Engel, E Kaunitz, JD Akiba, Y AF Wang, Joon-Ho Inoue, Takuya Higashiyama, Masaaki Guth, Paul H. Engel, Eli Kaunitz, Jonathan D. Akiba, Yasutada TI Umami Receptor Activation Increases Duodenal Bicarbonate Secretion via Glucagon-Like Peptide-2 Release in Rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID VASOACTIVE INTESTINAL POLYPEPTIDE; PIG SMALL-INTESTINE; ENTEROENDOCRINE CELLS; TASTE RECEPTORS; GLP-2 RECEPTOR; GUT; ACID; STIMULATION; MECHANISMS; TRANSPORT AB Luminal nutrient chemosensing during meal ingestion is mediated by intestinal endocrine cells, which regulate secretion and motility via the release of gut hormones. We have reported that luminal coperfusion of L-Glu and IMP, common condiments providing the umami or proteinaceous taste, synergistically increases duodenal bicarbonate secretion (DBS) possibly via taste receptor heterodimers, taste receptor type 1, member 1 (T1R1)/R3. We hypothesized that glucose-dependent insulinotropic peptide (GIP) or glucagon-like peptide (GLP) is released by duodenal perfusion with L-Glu/IMP. We measured DBS with pH and CO(2) electrodes through a perfused rat duodenal loop in vivo. GIP, exendin (Ex)-4 (GLP-1 receptor agonist), or GLP-2 was intravenously infused (0.01-1 nmol/kg/h). L-Glu (10 mM) and IMP (0.1 mM) were luminally perfused with or without bolus intravenous injection (3 or 30 nmol/kg) of the receptor antagonists Pro(3)GIP, Ex-3(9-39), or GLP-2(3-33). GIP or GLP-2 infusion dose-dependently increased DBS, whereas Ex-4 infusion gradually decreased DBS. Luminal perfusion of L-Glu/IMP increased DBS, with no effect of Pro(3)GIP or Ex-3(9-39), whereas GLP-2(3-33) inhibited L-Glu/IMP-induced DBS. Vasoactive intestinal peptide (VIP)(6-28) intravenously or N(G)-nitro-L-arginine methyl ester coperfusion inhibited the effect of L-Glu/IMP. Perfusion of L-Glu/IMP increased portal venous concentrations of GLP-2, followed by a delayed increase of GLP-1, with no effect on GIP release. GLP-1/2 and T1R1/R3 were expressed in duodenal endocrine-like cells. These results suggest that luminal L-Glu/IMP-induced DBS is mediated via GLP-2 release and receptor activation followed by VIP and nitric oxide release. Because GLP-1 is insulinotropic and GLP-2 is intestinotrophic, umami receptor activation may have additional benefits in glucose metabolism and duodenal mucosal protection and regeneration. C1 [Wang, Joon-Ho; Inoue, Takuya; Higashiyama, Masaaki; Kaunitz, Jonathan D.; Akiba, Yasutada] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Engel, Eli] Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Kaunitz, Jonathan D.; Akiba, Yasutada] Brentwood Biomed Res Inst, Los Angeles, CA USA. RP Akiba, Y (reprint author), W Los Angeles VA Med Ctr, 11301 Wilshire Blvd,Bldg 114,Suite 217, Los Angeles, CA 90073 USA. EM yakiba@mednet.ucla.edu FU Ajinomoto, Inc. (Tokyo, Japan); Department of Veterans Affairs Merit Review Award; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK54221, P30-DK0413] FX This work was supported by a research grant from Ajinomoto, Inc. (Tokyo, Japan) (to Y.A.); a Department of Veterans Affairs Merit Review Award (to J.D.K.); the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant R01-DK54221] (to J.D.K.); and the Animal Core of the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant P30-DK0413] (to J. E. Rozengurt). NR 42 TC 38 Z9 39 U1 1 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2011 VL 339 IS 2 BP 464 EP 473 DI 10.1124/jpet.111.184788 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 840TS UT WOS:000296464800016 PM 21846840 ER PT J AU Deyo, RA Smith, DHM Johnson, ES Donovan, M Tillotson, CJ Yang, XH Petrik, AF Dobscha, SK AF Deyo, Richard A. Smith, David H. M. Johnson, Eric S. Donovan, Marilee Tillotson, Carrie J. Yang, Xiuhai Petrik, Amanda F. Dobscha, Steven K. TI Opioids for Back Pain Patients: Primary Care Prescribing Patterns and Use of Services SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article DE Analgesics; Back Pain; Pain Control; Quality of Health Care ID CHRONIC NONCANCER PAIN; UNITED-STATES; MENTAL-HEALTH; TRENDS; PRESCRIPTIONS; ASSOCIATION; INDIVIDUALS; DISORDERS; WORKERS; ABUSE AB Background: Opioid prescribing for noncancer pain has increased dramatically. We examined whether the prevalence of unhealthy lifestyles, psychologic distress, health care utilization, and co-prescribing of sedative-hypnotics increased with increasing duration of prescription opioid use. Methods: We analyzed electronic data for 6 months before and after an index visit for back pain in a managed care plan. Use of opioids was characterized as "none," "acute" (<= 90 days), " episodic," or "long term." Associations with lifestyle factors, psychologic distress, and utilization were adjusted for demographics and comorbidity. Results: There were 26,014 eligible patients. Of these, 61% received a course of opioids, and 19% were long-term users. Psychologic distress, unhealthy lifestyles, and utilization were associated incrementally with duration of opioid prescription, not just with chronic use. Among long-term opioid users, 59% received only short-acting drugs; 39% received both long-and short-acting drugs; and 44% received a sedative-hypnotic. Of those with any opioid use, 36% had an emergency visit. Conclusions: Prescription of opioids was common among patients with back pain. The prevalence of psychologic distress, unhealthy lifestyles, and health care utilization increased incrementally with duration of use. Coprescribing sedative-hypnotics was common. These data may help in predicting long-term opioid use and improving the safety of opioid prescribing. (J Am Board Fam Med 2011;24:717-727.) C1 [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97239 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR USA. [Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR USA. [Deyo, Richard A.; Tillotson, Carrie J.] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Inst, Portland, OR USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR USA. [Deyo, Richard A.; Smith, David H. M.; Johnson, Eric S.; Donovan, Marilee; Yang, Xiuhai; Petrik, Amanda F.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Dobscha, Steven K.] Portland VA Med Ctr, Ctr Study Comorbid Mental & Phys Disorders, Portland, OR USA. RP Deyo, RA (reprint author), Oregon Hlth & Sci Univ, Dept Family Med, Mail Code FM,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM deyor@ohsu.edu FU Oregon Clinical and Translational Research Institute [UL1 RR024140]; National Center for Research Resources, National Institutes of Health; National Institutes of Health Roadmap for Medical Research FX This study was made possible with support from the Oregon Clinical and Translational Research Institute grant no. UL1 RR024140; from the National Center for Research Resources, a component of the National Institutes of Health; and the National Institutes of Health Roadmap for Medical Research. NR 31 TC 48 Z9 49 U1 1 U2 6 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD NOV-DEC PY 2011 VL 24 IS 6 BP 717 EP 727 DI 10.3122/jabfm.2011.06.100232 PG 11 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 849UI UT WOS:000297150400016 PM 22086815 ER PT J AU Nace, DA Perera, S Handler, SM Muder, R Hoffman, EL AF Nace, David A. Perera, Subashan Handler, Steven M. Muder, Robert Hoffman, Erika L. TI Increasing Influenza and Pneumococcal Immunization Rates in a Nursing Home Network SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Nursing homes; immunizations; influenza; health care workers; pneumococcal vaccine ID LONG-TERM-CARE; RANDOMIZED CONTROLLED-TRIAL; QUALITY IMPROVEMENT; UNITED-STATES; VACCINATION RATES; WORKERS; STAFF; HOSPITALIZATIONS; PERFORMANCE; MORTALITY AB Introduction and Rationale: Influenza and pneumonia remain serious health concerns for long-term care (LTC) residents. Vaccination of LTC residents and health care workers are reasonable preventive strategies, although most facilities fall short of Healthy People 2010 goals. Improving immunization rates across multiple LTC facilities remains an elusive challenge. This quality improvement study sought to improve immunization rates across 6 LTC facilities and identify persistent barriers to better performance. Methods: In 2002, 6 facilities associated with the University of Pittsburgh Institute on Aging established a quality improvement network addressing immunization rates. The facilities were provided with a written educational toolkit and shared information through an e-mail distribution list. To help determine optimal program structure in future years, 3 of the facilities participated in a single half-day collaborative training session. Change in immunization rates from baseline to year 2 were compared between those participating in the collaborative training and those not participating. Barriers to improved performance were sought from all groups through focus group analysis. Results: Facilities participating in the single collaborative training program improved immunization rates modestly, whereas facilities not participating in the collaborative training saw decreases in immunization rates. Staff turnover was cited as a significant barrier to improved performance. Discussion: It may be possible to improve immunization rates in LTC facilities, at least modestly, using a collaborative training process. Staff turnover may be an important barrier to improved LTC immunization rates. (J Am Med Dir Assoc 2011; 12: 678-684) C1 [Nace, David A.; Perera, Subashan; Handler, Steven M.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Sch Med, Pittsburgh, PA 15213 USA. [Perera, Subashan] Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Handler, Steven M.; Muder, Robert; Hoffman, Erika L.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Nace, DA (reprint author), Univ Pittsburgh, Dept Med, Div Geriatr Med, Sch Med, 3471 5th Ave,Suite 500, Pittsburgh, PA 15213 USA. EM naceda@upmc.edu RI Nace, David/D-2638-2014; Perera, Subashan/D-7603-2014; OI Handler, Steven/0000-0002-3940-3224 FU American Medical Directors Association Foundation/Pfizer FX This project was funded by the 2002 American Medical Directors Association Foundation/Pfizer Quality Improvement Awards. NR 41 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 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD NOV PY 2011 VL 12 IS 9 BP 678 EP 684 DI 10.1016/j.jamda.2010.05.002 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 850ZT UT WOS:000297238800012 PM 21450182 ER PT J AU Leuschner, F Dutta, P Gorbatov, R Novobrantseva, TI Donahoe, JS Courties, G Lee, KM Kim, JI Markmann, JF Marinelli, B Panizzi, P Lee, WW Iwamoto, Y Milstein, S Epstein-Barash, H Cantley, W Wong, J Cortez-Retamozo, V Newton, A Love, K Libby, P Pittet, MJ Swirski, FK Koteliansky, V Langer, R Weissleder, R Anderson, DG Nahrendorf, M AF Leuschner, Florian Dutta, Partha Gorbatov, Rostic Novobrantseva, Tatiana I. Donahoe, Jessica S. Courties, Gabriel Lee, Kang Mi Kim, James I. Markmann, James F. Marinelli, Brett Panizzi, Peter Lee, Won Woo Iwamoto, Yoshiko Milstein, Stuart Epstein-Barash, Hila Cantley, William Wong, Jamie Cortez-Retamozo, Virna Newton, Andita Love, Kevin Libby, Peter Pittet, Mikael J. Swirski, Filip K. Koteliansky, Victor Langer, Robert Weissleder, Ralph Anderson, Daniel G. Nahrendorf, Matthias TI Therapeutic siRNA silencing in inflammatory monocytes in mice SO NATURE BIOTECHNOLOGY LA English DT Article ID LIPID-LIKE MATERIALS; MYOCARDIAL-INFARCTION; SPLENIC RESERVOIR; IN-VIVO; MACROPHAGES; CCR2; DELIVERY; CANCER; ATHEROSCLEROSIS; PROGRESSION AB Excessive and prolonged activity of inflammatory monocytes is a hallmark of many diseases with an inflammatory component. In such conditions, precise targeting of these cells could be therapeutically beneficial while sparing many essential functions of the innate immune system, thus limiting unwanted effects. Inflammatory monocytes-but not the noninflammatory subset-depend on the chemokine receptor CCR2 for localization to injured tissue. Here we present an optimized lipid nanoparticle and a CCR2-silencing short interfering RNA that, when administered systemically in mice, show rapid blood clearance, accumulate in spleen and bone marrow, and localize to monocytes. Efficient degradation of CCR2 mRNA in monocytes prevents their accumulation in sites of inflammation. Specifically, the treatment attenuates their number in atherosclerotic plaques, reduces infarct size after coronary artery occlusion, prolongs normoglycemia in diabetic mice after pancreatic islet transplantation, and results in reduced tumor volumes and lower numbers of tumor-associated macrophages. C1 [Leuschner, Florian; Dutta, Partha; Gorbatov, Rostic; Donahoe, Jessica S.; Courties, Gabriel; Marinelli, Brett; Iwamoto, Yoshiko; Cortez-Retamozo, Virna; Newton, Andita; Pittet, Mikael J.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Leuschner, Florian; Dutta, Partha; Gorbatov, Rostic; Donahoe, Jessica S.; Courties, Gabriel; Marinelli, Brett; Iwamoto, Yoshiko; Cortez-Retamozo, Virna; Newton, Andita; Pittet, Mikael J.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA USA. [Novobrantseva, Tatiana I.; Milstein, Stuart; Epstein-Barash, Hila; Cantley, William; Wong, Jamie; Koteliansky, Victor] Alnylam Pharmaceut, Cambridge, MA USA. [Lee, Kang Mi; Kim, James I.; Markmann, James F.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Panizzi, Peter] Auburn Univ, Harrison Sch Pharm, Dept Pharmacal Sci, Auburn, AL 36849 USA. [Lee, Won Woo] Seoul Natl Univ, Bundang Hosp, Dept Nucl Med, Seoul, South Korea. [Love, Kevin; Langer, Robert; Anderson, Daniel G.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Langer, Robert; Anderson, Daniel G.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Langer, Robert; Anderson, Daniel G.] MIT, Div Hlth Sci Technol, Cambridge, MA 02139 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; mnahrendorf@mgh.harvard.edu RI Lee, Won Woo/J-5589-2012; OI Panizzi, Peter/0000-0003-0141-8807 FU US National Institutes of Health [R01-HL096576, R01-HL095629, R01-EB006432, T32-CA79443, U24-CA92782, P50-CA86355, HHSN268201000044C, R01-CA132091, R01-CA115527, R37-EB000244]; Deutsche Herzstiftung; SNUBH Research Fund [02-2007-013] FX The authors thank M. Waring, A. Chicoine and the Ragon Institute (MGH) for cell sorting, the CSB Mouse Imaging Program (P. Waterman, B. Sena) and B. Bettencourt for designing initial sets of siRNA. We acknowledge the small, medium and large scale RNA synthesis groups at Alnylam as well as analytical, duplex annealing and QC groups for synthesizing and characterizing RNAs. This work was funded in part by grants from the US National Institutes of Health R01-HL096576, R01-HL095629 (M.N.); R01-EB006432, T32-CA79443, U24-CA92782, P50-CA86355, HHSN268201000044C (R.W.); R01-CA132091, R01-CA115527, R37-EB000244 (R.L.); Deutsche Herzstiftung (F.L.); and the SNUBH Research Fund 02-2007-013 (W.W.L.). NR 43 TC 270 Z9 275 U1 4 U2 102 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 NOV PY 2011 VL 29 IS 11 BP 1005 EP U73 DI 10.1038/nbt.1989 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 845CT UT WOS:000296801300021 PM 21983520 ER PT J AU Short, EB Borckardt, JJ Anderson, BS Frohman, H Beam, W Reeves, ST George, MS AF Short, E. Baron Borckardt, Jeffrey J. Anderson, Berry S. Frohman, Heather Beam, William Reeves, Scott T. George, Mark S. TI Ten sessions of adjunctive left prefrontal rTMS significantly reduces fibromyalgia pain: A randomized, controlled pilot study SO PAIN LA English DT Article DE Depression; Fibromyalgia; Pain; Tender points; Transcranial magnetic stimulation ID TRANSCRANIAL MAGNETIC STIMULATION; MAJOR DEPRESSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; CHRONIC WIDESPREAD PAIN; DOUBLE-BLIND; CLINICAL-TRIAL; MULTICENTER; EFFICACY; CORTEX; MILNACIPRAN AB Transcranial magnetic stimulation (TMS) of the prefrontal cortex can cause changes in acute pain perception. Several weeks of daily left prefrontal TMS has been shown to treat depression. We recruited 20 patients with fibromyalgia, defined by American College of Rheumatology criteria, and randomized them to receive 4000 pulses at 10 Hz TMS (n = 10), or sham TMS (n = 10) treatment for 10 sessions over 2 weeks along with their standard medications, which were fixed and stable for at least 4 weeks before starting sessions. Subjects recorded daily pain, mood, and activity. Blinded raters assessed pain, mood, functional status, and tender points weekly with the Brief Pain Inventory, Hamilton Depression Rating Scale, and Fibromyalgia Impact Questionnaire. No statistically significant differences between groups were observed. Patients who received active TMS had a mean 29% (statistically significant) reduction in pain symptoms in comparison to their baseline pain. Sham TMS participants had a 4% nonsignificant change in daily pain from their baseline pain. At 2 weeks after treatment, there was a significant improvement in depression symptoms in the active group compared to baseline. Pain reduction preceded antidepressant effects. TMS was well tolerated, with few side effects. Further studies that address study limitations are needed to determine whether daily prefrontal TMS may be an effective, durable, and clinically useful treatment for fibromyalgia symptoms. (C) 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Short, E. Baron; Borckardt, Jeffrey J.; Frohman, Heather; Beam, William; George, Mark S.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Brain Stimulat Lab, Charleston, SC 29425 USA. [Borckardt, Jeffrey J.; Reeves, Scott T.] Med Univ S Carolina, Dept Anesthesia & Perioperat Med, Charleston, SC 29425 USA. [Anderson, Berry S.] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Short, EB (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Brain Stimulat Lab, 67 President St,POB 250861, Charleston, SC 29425 USA. EM shorteb@musc.edu FU Office of the Provost and Vice President for Research [P60 AR049459] FX Funding for this pilot project, under Multidisciplinary Clinical Research Center Grant P60 AR049459, was generously provided by the Office of the Provost and Vice President for Research. ClinicalTrials.gov identifier NCT00523302. NR 51 TC 34 Z9 37 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 2011 VL 152 IS 11 BP 2477 EP 2484 DI 10.1016/j.pain.2011.05.033 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 842AB UT WOS:000296556200009 PM 21764215 ER PT J AU Obara, I Tochiki, KK Geranton, SM Carr, FB Lumb, BM Liu, QS Hunt, SP AF Obara, Ilona Tochiki, Keri K. Geranton, Sandrine M. Carr, Fiona B. Lumb, Bridget M. Liu, Qingsong Hunt, Stephen P. TI Systemic inhibition of the mammalian target of rapamycin (mTOR) pathway reduces neuropathic pain in mice SO PAIN LA English DT Article DE Inflammatory pain; Local translation; mTOR; Neuropathic pain; Temsirolimus (CCI-779); Torin1 ID INDUCED THERMAL HYPERALGESIA; SPARED NERVE INJURY; 3-KINASE-AKT-MAMMALIAN TARGET; SYNAPTIC PLASTICITY; SIGNALING PATHWAY; LOCAL TRANSLATION; PROTEIN-SYNTHESIS; ANALOG CCI-779; GROWTH-FACTOR; MOUSE MODELS AB The management of neuropathic pain is unsatisfactory, and new treatments are required. Because the sensitivity of a subset of fast-conducting primary afferent nociceptors is thought to be regulated by the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, selectively targeting mTORC1 represents a new strategy for the control of chronic pain. Here we show that activated mTOR was expressed largely in myelinated sensory fibers in mouse and that inhibiting the mTORC1 pathway systemically alleviated mechanical hypersensitivity in mouse models of inflammatory and neuropathic pain. Specifically, systemic administration of mTORC1 inhibitor temsirolimus (CCI-779), both acutely (25 mg/kg i.p.) and chronically (4 daily 25 mg/kg i.p.), inhibited the mTORC1 pathway in sensory axons and the spinal dorsal horn and reduced mechanical and cold hypersensitivity induced by nerve injury. Moreover, systemic treatment with CCI-779 also reduced mechanical but not heat hypersensitivity in an inflammatory pain state. This treatment did not influence nociceptive thresholds in naive or sham-treated control animals. Also, there was no evidence for neuronal toxicity after repeated systemic treatment with CCI-779. Additionally, we show that acute and chronic i.p. administration of Torin1 (20 mg/kg), a novel ATP-competitive inhibitor targeting both mTORC1 and mTORC2 pathways, reduced the response to mechanical and cold stimuli in neuropathic mice. Our findings emphasize the importance of the mTORC1 pathway as a regulator of nociceptor sensitivity and therefore as a potential target for therapeutic intervention, particularly in chronic pain. (C) 2011 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved. C1 [Obara, Ilona; Tochiki, Keri K.; Geranton, Sandrine M.; Carr, Fiona B.; Hunt, Stephen P.] UCL, Dept Cell & Dev Biol, London WC1E 6BT, England. [Obara, Ilona] Polish Acad Sci, Inst Pharmacol, Dept Pain Pharmacol, PL-31343 Krakow, Poland. [Lumb, Bridget M.] Univ Bristol, Dept Physiol, Bristol BS8 1TD, Avon, England. [Liu, Qingsong] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Liu, Qingsong] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Obara, I (reprint author), UCL, Dept Cell & Dev Biol, Mortimer St, London WC1E 6BT, England. EM i.obara@ucl.ac.uk; hunt@ucl.ac.uk OI liu, qing song/0000-0002-7829-2547 FU Medical Research Council [G0801381] FX This research was supported by Grant G0801381 from the Medical Research Council. NR 63 TC 33 Z9 37 U1 1 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 2011 VL 152 IS 11 BP 2582 EP 2595 DI 10.1016/j.pain.2011.07.025 PG 14 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 842AB UT WOS:000296556200021 PM 21917376 ER PT J AU Hamel, LP Benchabane, M Nicole, MC Major, IT Morency, MJ Pelletier, G Beaudoin, N Sheen, J Seguin, A AF Hamel, Louis-Philippe Benchabane, Meriem Nicole, Marie-Claude Major, Ian T. Morency, Marie-Josee Pelletier, Gervais Beaudoin, Nathalie Sheen, Jen Seguin, Armand TI Stress-Responsive Mitogen-Activated Protein Kinases Interact with the EAR Motif of a Poplar Zinc Finger Protein and Mediate Its Degradation through the 26S Proteasome SO PLANT PHYSIOLOGY LA English DT Article ID LIGHT SIGNALING NETWORKS; MAP KINASE; ARABIDOPSIS-THALIANA; TRANSCRIPTION FACTOR; GENE-EXPRESSION; HYBRID POPLAR; PATHOGEN INTERACTIONS; MALACOSOMA-DISSTRIA; DISEASE RESISTANCE; AUX/IAA PROTEINS AB Mitogen-activated protein kinases (MAPKs) contribute to the establishment of plant disease resistance by regulating downstream signaling components, including transcription factors. In this study, we identified MAPK-interacting proteins, and among the newly discovered candidates was a Cys-2/His-2-type zinc finger protein named PtiZFP1. This putative transcription factor belongs to a family of transcriptional repressors that rely on an ERF-associated amphiphilic repression (EAR) motif for their repression activity. Amino acids located within this repression motif were also found to be essential for MAPK binding. Close examination of the primary protein sequence revealed a functional bipartite MAPK docking site that partially overlaps with the EAR motif. Transient expression assays in Arabidopsis (Arabidopsis thaliana) protoplasts suggest that MAPKs promote PtiZFP1 degradation through the 26S proteasome. Since features of the MAPK docking site are conserved among other EAR repressors, our study suggests a novel mode of defense mechanism regulation involving stress-responsive MAPKs and EAR repressors. C1 [Hamel, Louis-Philippe; Benchabane, Meriem; Nicole, Marie-Claude; Major, Ian T.; Morency, Marie-Josee; Pelletier, Gervais; Seguin, Armand] Nat Resources Canada, Canadian Forest Serv, Laurentian Forestry Ctr, Quebec City, PQ G1V 4C7, Canada. [Hamel, Louis-Philippe; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Beaudoin, Nathalie] Univ Sherbrooke, Dept Biol, Sherbrooke, PQ J1K 2R1, Canada. RP Seguin, A (reprint author), Nat Resources Canada, Canadian Forest Serv, Laurentian Forestry Ctr, Quebec City, PQ G1V 4C7, Canada. EM armand.seguin@nrcan-rncan.gc.ca OI Beaudoin, Nathalie/0000-0001-7835-4077 FU Genomics R&D Initiative of Canada; Natural Sciences and Engineering Research Council of Canada; Fonds Quebecois de la Recherche sur la Nature et les Technologies scholarships FX This work was supported by a grant from the Genomics R&D Initiative of Canada and the Natural Sciences and Engineering Research Council of Canada to A.S. and by Natural Sciences and Engineering Research Council of Canada and Fonds Quebecois de la Recherche sur la Nature et les Technologies scholarships to L.-P.H. NR 79 TC 13 Z9 14 U1 1 U2 18 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD NOV PY 2011 VL 157 IS 3 BP 1379 EP 1393 DI 10.1104/pp.111.178343 PG 15 WC Plant Sciences SC Plant Sciences GA 844BL UT WOS:000296722300031 PM 21873571 ER PT J AU Herschhorn, A Finzi, A Jones, DM Courter, JR Sugawara, A Smith, AB Sodroski, JG AF Herschhorn, Alon Finzi, Andres Jones, David M. Courter, Joel R. Sugawara, Akihiro Smith, Amos B., III Sodroski, Joseph G. TI An Inducible Cell-Cell Fusion System with Integrated Ability to Measure the Efficiency and Specificity of HIV-1 Entry Inhibitors SO PLOS ONE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; SMALL-MOLECULE INHIBITOR; CHEMOKINE RECEPTOR CCR5; HTLV-III/LAV ENVELOPE; CONFORMATIONAL-CHANGES; REVERSE-TRANSCRIPTASE; CXCR4 CORECEPTOR; POTENT INHIBITOR; AIDS PATIENTS; ASSAY SYSTEM AB HIV-1 envelope glycoproteins (Envs) mediate virus entry by fusing the viral and target cell membranes, a multi-step process that represents an attractive target for inhibition. Entry inhibitors with broad-range activity against diverse isolates of HIV-1 may be extremely useful as lead compounds for the development of therapies or prophylactic microbicides. To facilitate the identification of such inhibitors, we have constructed a cell-cell fusion system capable of simultaneously monitoring inhibition efficiency and specificity. In this system, effector cells stably express a tetracycline-controlled transactivator (tTA) that enables tightly inducible expression of both HIV-1 Env and the Renilla luciferase (R-Luc) reporter protein. Target cells express the HIV-1 receptors, CD4 and CCR5, and carry the firefly luciferase (F-Luc) reporter gene under the control of a tTA-responsive promoter. Thus, Env-mediated fusion of these two cell types allows the tTA to diffuse to the target cell and activate the expression of the F-Luc protein. The efficiency with which an inhibitor blocks cell-cell fusion is measured by a decrease in the F-Luc activity, while the specificity of the inhibitor is evaluated by its effect on the R-Luc activity. The system exhibited a high dynamic range and high Z'-factor values. The assay was validated with a reference panel of inhibitors that target different steps in HIV-1 entry, yielding inhibitory concentrations comparable to published virus inhibition data. Our system is suitable for large-scale screening of chemical libraries and can also be used for detailed characterization of inhibitory and cytotoxic properties of known entry inhibitors. C1 [Herschhorn, Alon; Finzi, Andres; Sodroski, Joseph G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Immunol Canc & AIDS, Boston, MA 02115 USA. [Herschhorn, Alon; Finzi, Andres; Sodroski, Joseph G.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Jones, David M.; Courter, Joel R.; Sugawara, Akihiro; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Sodroski, Joseph G.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Herschhorn, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Immunol Canc & AIDS, 44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu OI Sugawara, Akihiro/0000-0003-1266-7497 FU American Foundation for AIDS Research [107431-45-RFRL]; Japan Society for the Promotion of Science (JSPS); National Institutes of Health [GM56550, AI24755, AI67854, AI60354]; International AIDS Vaccine Initiative FX A.F. was supported by an American Foundation for AIDS Research Mathilde Krim Fellowship in Basic Biomedical Research # 107431-45-RFRL. A.S. was supported by a Japan Society for the Promotion of Science (JSPS) research fellowship. The study was supported by the National Institutes of Health (grants GM56550, AI24755, AI67854 and AI60354), the International AIDS Vaccine Initiative, and the late William F. McCarty-Cooper. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 72 TC 5 Z9 5 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 1 PY 2011 VL 6 IS 11 AR e26731 DI 10.1371/journal.pone.0026731 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 849UN UT WOS:000297150900028 PM 22069466 ER PT J AU Liao, YH Tang, JS Deng, QJ Deng, YW Luo, T Wang, XY Chen, HX Liu, TQ Chen, XG Brody, AL Hao, W AF Liao, Yanhui Tang, Jinsong Deng, Qijian Deng, Yongwen Luo, Tao Wang, Xuyi Chen, Hongxian Liu, Tieqiao Chen, Xiaogang Brody, Arthur L. Hao, Wei TI Bilateral Fronto-Parietal Integrity in Young Chronic Cigarette Smokers: A Diffusion Tensor Imaging Study SO PLOS ONE LA English DT Article ID WHITE-MATTER ABNORMALITIES; SPINAL-CORD NEURONS; ANISOTROPIC WATER DIFFUSION; MAGNETIC-RESONANCE; MICROSTRUCTURAL INTEGRITY; HUNTINGTONS-DISEASE; TOBACCO CONTROL; NICOTINE; BRAIN; SMOKING AB Background: Cigarette smoking continues to be the leading cause of preventable morbidity and mortality in China and other countries. Previous studies have demonstrated gray matter loss in chronic smokers. However, only a few studies assessed the changes of white matter integrity in this group. Based on those previous reports of alterations in white matter integrity in smokers, the aim of this study was to examine the alteration of white matter integrity in a large, well-matched sample of chronic smokers and non-smokers. Methodology/Principal Findings: Using in vivo diffusion tensor imaging (DTI) to measure the differences of whole-brain white matter integrity between 44 chronic smoking subjects (mean age, 28.0 +/- 5.6 years) and 44 healthy age- and sex-matched comparison non-smoking volunteers (mean age, 26.3 +/- 5.8 years). DTI was performed on a 3-Tesla Siemens scanner (Allegra; Siemens Medical System). The data revealed that smokers had higher fractional anisotropy (FA) than healthy non-smokers in almost symmetrically bilateral fronto-parietal tracts consisting of a major white matter pathway, the superior longitudinal fasciculus (SLF). Conclusion/Significance: We found the almost symmetrically bilateral fronto-parietal whiter matter changes in a relatively large sample of chronic smokers. These findings support the hypothesis that chronic cigarette smoking involves alterations of bilateral fronto-parietal connectivity. C1 [Liao, Yanhui; Tang, Jinsong; Deng, Qijian; Luo, Tao; Wang, Xuyi; Chen, Hongxian; Liu, Tieqiao; Chen, Xiaogang; Hao, Wei] Cent S Univ, Xiangya Hosp 2, Mental Hlth Inst, Changsha, Hunan, Peoples R China. [Deng, Yongwen] Peoples Hosp Hunan Prov, Dept Neurosurg, Changsha, Hunan, Peoples R China. [Brody, Arthur L.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Brody, Arthur L.] Greater Los Angeles VA Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Brody, Arthur L.] Greater Los Angeles VA Healthcare Syst, Dept Res, Los Angeles, CA USA. RP Liao, YH (reprint author), Cent S Univ, Xiangya Hosp 2, Mental Hlth Inst, Changsha, Hunan, Peoples R China. EM abrody@ucla.edu; weihaochangsha@gmail.com RI Liao, Yanhui/L-1590-2016 OI Liao, Yanhui/0000-0003-4735-3252 FU Central Colleges basic scientific research operating expenses; National Key Technology R&D Program in the 11th Five-Year Plan of China [2011QNZT170, 2007BAI07B01]; Natural Science Foundation of China [81100996, 30971050, 30900486, 81130020]; National Key Basic Research and Development Program(NKBRDP) (973) [2009CB522000]; Hunan Provincial Natural Science Foundation of China [10JJ5038]; Tobacco-Related Disease Research Program [19XT-0135]; National Institute on Drug Abuse [R01 DA20872]; China Scholarship Council; University of Cambridge; Behavioural and Clinical Neuroscience Institute; Veterans Affairs Type I Merit Review Award; Richard Metzner Chair in Clinical Neuropharmacology FX This work was supported by grants from the Central Colleges basic scientific research operating expenses. 2011QNZT170, National Key Technology R&D Program in the 11th Five-Year Plan of China (2007BAI07B01), Natural Science Foundation of China (81100996, 30971050, 30900486, 81130020), National Key Basic Research and Development Program(NKBRDP) (973, 2009CB522000) and from Hunan Provincial Natural Science Foundation of China (10JJ5038). Tobacco-Related Disease Research Program (19XT-0135), the National Institute on Drug Abuse (R01 DA20872), a Veterans Affairs Type I Merit Review Award, and an endowment from the Richard Metzner Chair in Clinical Neuropharmacology. Yanhui Liao is supported by a fellowship from the China Scholarship Council to study at University of Cambridge, Behavioural and Clinical Neuroscience Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 20 Z9 21 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 1 PY 2011 VL 6 IS 11 AR e26460 DI 10.1371/journal.pone.0026460 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 849UN UT WOS:000297150900014 PM 22069452 ER PT J AU Zhang, YY Zhen, Y Dong, YL Xu, ZP Yue, Y Golde, TE Tanzi, RE Moir, RD Xie, ZC AF Zhang, Yiying Zhen, Yu Dong, Yuanlin Xu, Zhipeng Yue, Yun Golde, Todd E. Tanzi, Rudolph E. Moir, Robert D. Xie, Zhongcong TI Anesthetic Propofol Attenuates the Isoflurane-Induced Caspase-3 Activation and A beta Oligomerization SO PLOS ONE LA English DT Article ID NITROUS OXIDE ANESTHESIA; ALZHEIMERS-DISEASE; SPATIAL MEMORY; CEREBRAL-ISCHEMIA; INDUCED APOPTOSIS; DNA-DAMAGE; AGED RATS; IN-VITRO; BRAIN; NEUROPROTECTION AB Accumulation and deposition of beta-amyloid protein (A beta) are the hallmark features of Alzheimer's disease. The inhalation anesthetic isoflurane has been shown to induce caspase activation and increase A beta accumulation. In addition, recent studies suggest that isoflurane may directly promote the formation of cytotoxic soluble A beta oligomers, which are thought to be the key pathological species in AD. In contrast, propofol, the most commonly used intravenous anesthetic, has been reported to have neuroprotective effects. We therefore set out to compare the effects of isoflurane and propofol alone and in combination on caspase-3 activation and A beta oligomerization in vitro and in vivo. Naive and stably-transfected H4 human neuroglioma cells that express human amyloid precursor protein, the precursor for A beta; neonatal mice; and conditioned cell culture media containing secreted human A beta 40 or A beta 42 were treated with isoflurane and/or propofol. Here we show for the first time that propofol can attenuate isoflurane-induced caspase-3 activation in cultured cells and in the brain tissues of neonatal mice. Furthermore, propofol-mediated caspase inhibition occurred when there were elevated levels of A beta. Finally, isoflurane alone induces A beta 42, but not A beta 40, oligomerization, and propofol can inhibit the isoflurane-mediated oligomerization of A beta 42. These data suggest that propofol may mitigate the caspase-3 activation by attenuating the isoflurane-induced A beta 42 oligomerization. Our findings provide novel insights into the possible mechanisms of isoflurane-induced neurotoxicity that may aid in the development of strategies to minimize potential adverse effects associated with the administration of anesthetics to patients. C1 [Zhang, Yiying; Zhen, Yu; Dong, Yuanlin; Xu, Zhipeng; Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA USA. [Zhang, Yiying; Zhen, Yu; Dong, Yuanlin; Xu, Zhipeng; Tanzi, Rudolph E.; Moir, Robert D.; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA USA. [Zhang, Yiying; Zhen, Yu; Dong, Yuanlin; Xu, Zhipeng; Tanzi, Rudolph E.; Moir, Robert D.; Xie, Zhongcong] Massachusetts Gen Hosp, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA USA. [Zhen, Yu] Capital Med Univ, Dept Anesthesia, Beijing Friendship Hosp, Beijing, Peoples R China. [Yue, Yun] Capital Med Univ, Dept Anesthesia, Beijing Chaoyang Hosp, Beijing, Peoples R China. [Golde, Todd E.] Univ Florida, Dept Neurosci, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA. RP Zhang, YY (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA USA. EM zxie@partners.org FU National Institutes of Health (Bethesda, Maryland) [K08 NS048140, R21 AG029856, R01 GM088801]; American Geriatrics Society (New York, New York); Alzheimer's Association (Chicago, Illinois); National Natural Science Foundation of China [30928026, 81000474/H0902] FX This study was supported by National Institutes of Health grants (Bethesda, Maryland) (K08 NS048140, R21 AG029856 and R01 GM088801); American Geriatrics Society Jahnigen Award (New York, New York); Investigator-Initiated Research Grant from Alzheimer's Association (Chicago, Illinois) to ZX; National Natural Science Foundation of China (30928026) to ZX and YY, and National Natural Science Foundation of China (81000474/H0902) to Y. Zhen. The Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School provided the cost of anesthetic isoflurane. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 31 Z9 33 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 1 PY 2011 VL 6 IS 11 AR e27019 DI 10.1371/journal.pone.0027019 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 849UN UT WOS:000297150900043 PM 22069482 ER PT J AU Zhu, XX Liu, Q Wang, MM Liang, MR Yang, X Xu, X Zou, HJ Qiu, JH AF Zhu, Xiaoxia Liu, Qiong Wang, Meimei Liang, Minrui Yang, Xue Xu, Xue Zou, Hejian Qiu, Jianhua TI Activation of Sirt1 by Resveratrol Inhibits TNF-alpha Induced Inflammation in Fibroblasts SO PLOS ONE LA English DT Article ID NF-KAPPA-B; OBSTRUCTIVE PULMONARY-DISEASE; SMOOTH-MUSCLE-CELLS; RHEUMATOID-ARTHRITIS; MEDIATED INFLAMMATION; PROTEIN TRANSLATION; TRANS-RESVERATROL; RELA ACETYLATION; IN-VITRO; APOPTOSIS AB Inflammation is one of main mechanisms of autoimmune disorders and a common feature of most diseases. Appropriate suppression of inflammation is a key resolution to treat the diseases. Sirtuin1 (Sirt1) has been shown to play a role in regulation of inflammation. Resveratrol, a potent Sirt1 activator, has anti-inflammation property. However, the detailed mechanism is not fully understood. In this study, we investigated the anti-inflammation role of Sirt1 in NIH/3T3 fibroblast cell line. Upregulation of matrix metalloproteinases 9 (MMP-9), interleukin-1beta (IL-1 beta), IL-6 and inducible nitric oxide synthase (iNOS) were induced by tumor necrosis factor alpha (TNF-alpha) in 3T3 cells and resveratrol suppressed overexpression of these pro-inflammatory molecules in a dose-dependent manner. Knockdown of Sirt1 by RNA interference caused 3T3 cells susceptible to TNF-alpha stimulation and diminished anti-inflammatory effect of resveratrol. We also explored potential anti-inflammatory mechanisms of resveratrol. Resveratrol reduced NF-kappa B subunit RelA/p65 acetylation, which is notably Sirt1 dependent. Resveratrol also attenuated phosphorylation of mammalian target of rapamycin (mTOR) and S6 ribosomal protein (S6RP) while ameliorating inflammation. Our data demonstrate that resveratrol inhibits TNF-alpha-induced inflammation via Sirt1. It suggests that Sirt1 is an efficient target for regulation of inflammation. This study provides insight on treatment of inflammation-related diseases. C1 [Zhu, Xiaoxia; Liang, Minrui; Yang, Xue; Xu, Xue; Zou, Hejian] Fudan Univ, Shanghai Med Coll, Huashan Hosp, Div Rheumatol, Shanghai, Peoples R China. [Zhu, Xiaoxia; Liu, Qiong; Liang, Minrui; Yang, Xue; Xu, Xue; Zou, Hejian] Fudan Univ, Inst Rheumatol Immunol & Allergy, Huashan Hosp, Shanghai Med Coll, Shanghai, Peoples R China. [Liu, Qiong] Fudan Univ, Shanghai Med Coll, Dept Human Anat Histol & Embryol, Shanghai, Peoples R China. [Wang, Meimei] Dongnan Univ, Zhongda Hosp, Div Rheumatol, Nanjing, Peoples R China. [Qiu, Jianhua] Harvard Univ, Dept Neurol & Radiol, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. RP Zhu, XX (reprint author), Fudan Univ, Shanghai Med Coll, Huashan Hosp, Div Rheumatol, Shanghai, Peoples R China. EM hjzou@fudan.edu.cn; jqiu@partners.org FU Program of Shanghai Subject Chief Scientist [11XD1401100]; National Natural Science Foundation of China [81072463] FX This work was supported by Program of Shanghai Subject Chief Scientist (NO. 11XD1401100) and National Natural Science Foundation of China (No. 81072463). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 77 TC 16 Z9 22 U1 2 U2 21 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 1 PY 2011 VL 6 IS 11 AR e27081 DI 10.1371/journal.pone.0027081 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 849UN UT WOS:000297150900049 PM 22069489 ER PT J AU Kuna, ST AF Kuna, Samuel T. TI Back to the Future or Forward to the Past? SO SLEEP LA English DT Editorial Material ID OBSTRUCTIVE SLEEP-APNEA; NERVE-STIMULATION; HYPOGLOSSAL NERVE; UPPER AIRWAY C1 [Kuna, Samuel T.] Philadelphia VA Med Ctr, Pulm Crit Care & Sleep Sect, Philadelphia, PA 19104 USA. [Kuna, Samuel T.] Univ Penn, Philadelphia, PA 19104 USA. RP Kuna, ST (reprint author), Philadelphia VA Med Ctr, Pulm Crit Care & Sleep Sect, 111P,3900 Woodland Av, Philadelphia, PA 19104 USA. EM skuna@mail.med.upenn.edu NR 14 TC 1 Z9 1 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD NOV 1 PY 2011 VL 34 IS 11 BP 1455 EP 1456 DI 10.5665/sleep.1370 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844DF UT WOS:000296727200003 PM 22043113 ER PT J AU Luckey, CJ Lu, Y Marto, JA AF Luckey, C. John Lu, Yu Marto, Jarrod A. TI Understanding the first steps in embryonic stem cell exit from the pluripotent state SO TRANSFUSION LA English DT Article ID SELF-RENEWAL; PHOSPHOPROTEOMICS; DIFFERENTIATION; ACTIVATION AB BACKGROUND: We are interested in understanding how a given cell type, in response to external cues from its environment, makes the decision to differentiate. In the case of mouse embryonic stem cells (mESCs), the key external factor that maintains their undifferentiated state is the cytokine leukemia inhibitory factor (LIF). LIF removal causes mESCs to exit their pluripotent state and differentiate into more restricted precursors. Although LIF is known to activate multiple different phosphorylation cascades, the mechanisms by which its removal leads to mESC differentiation are not well understood. STUDY DESIGN AND METHODS: In order to identify the molecular events that occur upon LIF removal, we developed a set of novel experimental approaches that allowed identification and quantification of global phosphorylation changes that occur when mESCs are deprived of LIF. These included growth of mESCs on permeable membranes and development of a robust and sensitive phospho-proteomics platform to quantify early signaling events. RESULTS: In addition to the well-characterized tyrosine 705 phosphorylation of STAT3, LIF removal results in the rapid phosphorylation of multiple other proteins known to regulate the mESC self-renewal on both tyrosine, serine, and threonine residues. We hypothesize that these unique posttranslational modifications help drive the exit of mESCs from the pluripotent state. CONCLUSIONS: Our data set the stage for future studies investigating the functional role of these phosphorylation events in mESCs. These studies were greatly facilitated by the National Blood Foundation, whose support in the crucial initiation phase of these studies was invaluable. C1 [Luckey, C. John] Brigham & Womens Hosp, Dept Pathol, Joint Program Transfus Med, Dept Canc Biol,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Luckey, CJ (reprint author), Brigham & Womens Hosp, Dept Pathol, Joint Program Transfus Med, Dept Canc Biol,Dana Farber Canc Inst, NRB Rm 652D,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cluckey@partners.org FU NHLBI NIH HHS [RC2 HL102815, R21 HL111866, RC2 HL102815-01]; NIAID NIH HHS [K08 AI063386, K08 AI063386-04, K08 AI063386-03] NR 24 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD NOV PY 2011 VL 51 SU 4 SI SI BP 118S EP 124S DI 10.1111/j.1537-2995.2011.03374.x PG 7 WC Hematology SC Hematology GA 851SH UT WOS:000297290700007 PM 22074622 ER PT J AU Chung, HJ Reiner, T Budin, G Min, C Liong, M Issadore, D Lee, H Weissleder, R AF Chung, Hyun Jung Reiner, Thomas Budin, Ghyslain Min, Changwook Liong, Monty Issadore, David Lee, Hakho Weissleder, Ralph TI Ubiquitous Detection of Gram-Positive Bacteria with Bioorthogonal Magnetofluorescent Nanoparticles SO ACS NANO LA English DT Article DE nanoparticles; bacteria; infection ID SELF-ASSEMBLED MONOLAYERS; MAGNETIC NANOPARTICLES; CANCER-CELLS; VANCOMYCIN; DAPTOMYCIN; INFECTIONS; BINDING; ANTIBIOTICS; ENTEROCOCCI AB The ability to rapidly diagnose gram-positive pathogenic bacteria would have far reaching biomedical and technological applications. Here we describe the bloorthogonal modification of small molecule antibiotics (vancomycin and daptomycin), which bind to the cell wall of gram-positive bacteria. The bound antibiotics conjugates can be reacted orthogonally with tetrazine-modified nanoparticles, via an almost Instantaneous cycloaddition, which subsequently renders the bacteria detectable by optical or magnetic sensing. We show that this approach is specific, selective, fast and biocompatible. Furthermore, it can be adapted to the detection of intracellular pathogens. Importantly, this strategy enables detection of entire classes of bacteria, a feat that is difficult to achieve using current antibody approaches. Compared to covalent nanoparticle conjugates, our bioorthogonal method demonstrated 1-2 orders of magnitude greater sensitivity. This bioorthogonal labeling method could ultimately be applied to a variety of other small molecules with specificity for infectious pathogens, enabling their detection and diagnosis. C1 [Chung, Hyun Jung; Reiner, Thomas; Budin, Ghyslain; Min, Changwook; Liong, Monty; Issadore, David; Lee, Hakho; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Lee, H (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM hlee@mgh.harvard.edu; rweissleder@mgh.harvard.edu RI Chung, Hyun Jung/J-3205-2014; Issadore, David/L-8451-2014; OI Reiner, Thomas/0000-0002-7819-5480 FU NHLBI [HHSN268201000044C]; NIBIB [R01-EB010011, R01-EB00462605A1]; German Academy of Sciences Leopoldina [LPDS 2009-24] FX We acknowledge S. Hilderbrand and M. Karver for their help with the synthesis of tetrazine, N. Sergeyev for the synthesis of cross-linked dextran iron oxide nanoparticles, I. Bagayev for help in confocal microscopy, J. Carlson for the helpful suggestions, and Y. Fisher-Jeffes for review of the manuscript. This work was funded in part by NHLBI Contract HHSN268201000044C and NIBIB Grants R01-EB010011 and R01-EB00462605A1. T.R. was supported by a grant from the German Academy of Sciences Leopoldina (LPDS 2009-24). NR 27 TC 58 Z9 58 U1 5 U2 59 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD NOV PY 2011 VL 5 IS 11 BP 8834 EP 8841 DI 10.1021/nn2029692 PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 849RR UT WOS:000297143300043 PM 21967150 ER PT J AU Ullal, AV Reiner, T Yang, KS Gorbatov, R Min, C Issadore, D Lee, H Weissleder, R AF Ullal, Adeeti V. Reiner, Thomas Yang, Katherine S. Gorbatov, Rostic Min, Changwook Issadore, David Lee, Hakho Weissleder, Ralph TI Nanoparticle-Mediated Measurement of Target-Drug Binding in Cancer Cells SO ACS NANO LA English DT Article DE nanoparticles; targeting; NMR; DMR; cancer; drugs; PARP ID DIPHOSPHATE-RIBOSE) POLYMERASE EXPRESSION; POLY(ADP-RIBOSE) POLYMERASE-1; PARP-1; INHIBITORS; PROTEINS; COMPLEX AB Responses to molecularly targeted therapies can be highly variable and depend on mutations, fluctuations in target protein levels In individual cells, and drug delivery. The ability to rapidly quantitate drug response in cells harvested from patients in a point-of-care setting would have far reaching Implications. Capitalizing on recent developments with miniaturized NMR technologies, we have developed a magnetic nanoparticle-based approach to directly measure both target expression and drug binding In scant human cells. The method involves covalent conjugation of the small-molecule drug to a magnetic nanoparticle that Is then used as a read-out for target expression and drug-binding affinity. Using poly(ADP-ribose) polymerase (PARP) inhibition as a model system, we developed an approach to distinguish differential expression of PARP in scant cells with excellent correlation to gold standards, the ability to mimic drug pharmacodynamics ex vivo through competitive target drug binding, and the potential to perform such measurements In clinical samples. C1 [Ullal, Adeeti V.; Reiner, Thomas; Yang, Katherine S.; Gorbatov, Rostic; Min, Changwook; Issadore, David; Lee, Hakho; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Ullal, Adeeti V.] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu RI Issadore, David/L-8451-2014; OI Reiner, Thomas/0000-0002-7819-5480 FU NSF; German National Academy of Sciences Leopoldina [LPDS 2009-24]; National Institutes of Health [R01-EB0044626, R01-EB010011, P50CA86355, U54CA151884]; TPEN [HHSN268201000044C] FX The authors thank N. Sergeyev for synthesizing the CLIO, B. Marinelli and K. Snyder for assisting with DMR measurements, J. Dunham with imaging, M. Etzrodt and V. Cortez-Retamozo for assistance with flow cytometry experiments, and C. Tassa and M. Liong for guidance on nanoparticle conjugations. We especially thank G. Thurber and J. Haun for many helpful discussions. A.V.U. was supported in part by an NSF fellowship. T.R. was supported by a grant from the German National Academy of Sciences Leopoldina (LPDS 2009-24). This work was supported in part by National Institutes of Health Grants R01-EB0044626, R01-EB010011, P50 grant P50CA86355, U54CA151884, and TPEN contract HHSN268201000044C. NR 39 TC 12 Z9 13 U1 1 U2 28 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD NOV PY 2011 VL 5 IS 11 BP 9216 EP 9224 DI 10.1021/nn203450p PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 849RR UT WOS:000297143300085 PM 21962084 ER PT J AU Fradley, MG Larson, MG Cheng, S McCabe, E Coglianese, E Shah, RV Levy, D Vasan, RS Wang, TJ AF Fradley, Michael G. Larson, Martin G. Cheng, Susan McCabe, Elizabeth Coglianese, Erin Shah, Ravi V. Levy, Daniel Vasan, Rarnachandran S. Wang, Thomas J. TI Reference Limits for N-Terminal-pro-B-Type Natriuretic Peptide in Healthy Individuals (from the Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BIOLOGICAL VARIATION; AGE; FAILURE; BNP; DYSFUNCTION; GENDER; ADULTS; IMPACT; SEX AB N-terminal pro B-type natriuretic peptide (NT-pro-BNP) is a commonly measured cardiovascular biomarker in ambulatory and hospital settings. Nonetheless, there are limited data regarding "normal" ranges for NT-pro-BNP in healthy subjects, despite the importance of such information for interpreting natriuretic peptide measurements. In this study, a healthy reference sample free of cardiovascular disease from the Framingham Heart Study Generation 3 cohort was examined; there were 2,285 subjects (mean age 38 years, 56% women). Plasma NT-pro-BNP levels were measured using the Roche Diagnostics Elecsys 2010 assay, and reference values (2.5th, 50th, and 97.5th quantiles) were determined using empiric and quantile regression methods. Gender, age, blood pressure, and body mass index accounted for approximately 33% of the interindividual variability in NT-pro-BNP in the reference sample. NT-pro-BNP values were substantially higher in women compared to men at every age, and levels increased with increasing age for both genders. Using quantile regression, the upper reference values (97.5th quantile) for NT proBNP were 42.5 to 106.4 pg/ml in men (depending on age) and 111.0 to 215.9 pg/ml in women. Intraindividual variability was assessed in an additional 12 healthy subjects, who had serial NT-pro-BNP measurements over 1 month. Intraclass correlation was 0.85, indicating that most of the variability in NT-pro-BNP concentrations was among rather than within subjects. However, the reference change value was 100%, suggesting that small proportional differences in NT-pro-BNP could be attributable to analytic variability. In conclusion, the reference limits obtained from this large, healthy, community-based sample may aid in the evaluation of NT-pro-BNP concentrations measured for clinical and research purposes. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:1341-1345) C1 [Fradley, Michael G.; McCabe, Elizabeth; Coglianese, Erin; Shah, Ravi V.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02215 USA. [Larson, Martin G.; Cheng, Susan; Levy, Daniel; Vasan, Rarnachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Cheng, Susan] Harvard Univ, Sch Med, Div Cardiovasc Med, Brigham & Womens Hosp, Boston, MA USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Levy, Daniel; Vasan, Rarnachandran S.] Boston Univ, Sch Med, Prevent Med & Cardiol Sect, Boston, MA 02118 USA. RP Wang, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02215 USA. EM tjwang@partners.org OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung and Blood Institute's Framingham Heart Study [NO1-HC-25195]; Siemens Healthcare Diagnostics, Deerfield, Illinois; Brahms AG, Hennigsdorf, Germany; [R01-HL086875] FX This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (NO1-HC-25195) and grant R01-HL086875.; Dr. Wang has been a coinvestigator on studies that have received assay support from Siemens Healthcare Diagnostics, Deerfield, Illinois, and Brahms AG, Hennigsdorf, Germany. NR 20 TC 34 Z9 36 U1 0 U2 5 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 NOV 1 PY 2011 VL 108 IS 9 BP 1341 EP 1345 DI 10.1016/j.amjcard.2011.06.057 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 846YM UT WOS:000296939100023 PM 21864812 ER PT J AU Quraishi, SA Blosser, SA Cherry, RA AF Quraishi, Sadeq A. Blosser, Sandralee A. Cherry, Robert A. TI BISPECTRAL INDEX MONITORING IN THE MANAGEMENT OF SEDATION IN AN INTENSIVE CARE UNIT PATIENT WITH LOCKED-IN SYNDROME SO AMERICAN JOURNAL OF CRITICAL CARE LA English DT Article ID CRITICALLY-ILL PATIENTS; ICU PATIENTS; LEVEL AB Locked-in syndrome is an extremely rare neurological state caused by injury of the ventral pons. The syndrome is characterized by quadriplegia and anarthria with concomitant preservation of cortical function. When a reversible underlying pathological abnormality is identified and managed aggressively, meaningful recovery is possible. Because patients retain consciousness through out their illness, a dependable method for titrating sedation may improve their quality of life. The case presented suggests that bispectral index monitoring may be a cost-effective and reliable method for managing sedation in patients with locked-in syndrome. (American Journal of Critical Care. 2011;20:491,487-490) C1 [Quraishi, Sadeq A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Quraishi, Sadeq A.] Harvard Univ, Sch Med, Boston, MA USA. [Blosser, Sandralee A.] Penn State Univ, Dept Anesthesiol, Coll Med, Hershey, PA USA. [Blosser, Sandralee A.; Cherry, Robert A.] Penn State Univ, Dept Surg, Coll Med, Hershey, PA USA. [Blosser, Sandralee A.] Penn State Univ, Dept Med, Coll Med, Hershey, PA USA. [Blosser, Sandralee A.] Penn State Milton S Hershey Med Ctr, Adult Crit Care Serv, Hershey, PA USA. [Cherry, Robert A.] Penn State Univ, Coll Med, Dept Publ Hlth Sci, Hershey, PA USA. [Cherry, Robert A.] Penn State Milton S Hershey Med Ctr, Ctr Shock Trauma, Hershey, PA USA. RP Quraishi, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRJ 402, Boston, MA 02114 USA. EM squraishi@partners.org NR 18 TC 0 Z9 1 U1 1 U2 1 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1062-3264 J9 AM J CRIT CARE JI Am. J. Crit. Care PD NOV 1 PY 2011 VL 20 IS 6 BP 487 EP 491 DI 10.4037/ajcc2011674 PG 5 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 843FK UT WOS:000296657500020 PM 22045147 ER PT J AU Hazin, R Coyer, M Lum, F Barazi, MK AF Hazin, Ribhi Coyer, Marcus Lum, Flora Barazi, Mohammed K. TI Revisiting Diabetes 2000: Challenges in Establishing Nationwide Diabetic Retinopathy Prevention Programs SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID NUTRITION EXAMINATION SURVEY; PREFERRED PRACTICE PATTERN; IMPAIRED FASTING GLUCOSE; TREATING RETINOPATHY; US POPULATION; UNITED-STATES; RISK-FACTORS; EYE DISEASE; FOLLOW-UP; MELLITUS AB PURPOSE: To evaluate the impact of the Diabetes 2000 program, an initiative launched by the American Academy of Ophthalmology in 1990 to improve nationwide screening of diabetic retinopathy (DR) and to reduce the prevalence and severity of the condition. DESIGN: Retrospective, observational case study of Diabetes 2000 program. METHODS: This is a perspective piece with a review of literature and personal opinions. RESULTS: Patients with diabetes are likely to see an increase in the disease burdens associated with DR unless effective programs for early detection and control of DR are implemented. CONCLUSIONS: Despite recent efforts to educate both patients and physicians alike about the importance of routine DR screening, the lessons learned from the Diabetes 2000 program illustrate the need for new strategies capable of improving accessibility to high-quality eye care, increasing involvement of primary care physicians in DR screening and encouraging at-risk individuals to seek testing. (Am J Ophthalmol 2011; 152:723-729. (C) 2011 by Elsevier Inc. All rights reserved.) C1 [Hazin, Ribhi] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02138 USA. [Coyer, Marcus; Barazi, Mohammed K.] Retina Grp Washington, Manassas, VA USA. [Coyer, Marcus] Walter Reed Army Med Ctr, Ophthalmol Serv, Washington, DC 20307 USA. [Lum, Flora] Amer Acad Ophthalmol, San Francisco, CA USA. RP Hazin, R (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02138 USA. EM rhazin@mail.harvard.edu NR 49 TC 16 Z9 16 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 2011 VL 152 IS 5 BP 723 EP 729 DI 10.1016/j.ajo.2011.06.022 PG 7 WC Ophthalmology SC Ophthalmology GA 840BK UT WOS:000296413100004 PM 21917235 ER PT J AU Robinson, TN Wu, DS Stiegmann, GV Moss, M AF Robinson, Thomas N. Wu, Daniel S. Stiegmann, Gregory V. Moss, Marc TI Frailty predicts increased hospital and six-month healthcare cost following colorectal surgery in older adults SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Association of VA Surgeons CY APR 10-12, 2011 CL Irvine, CA SP Assoc VA Surg DE Geriatric; Surgery; Financial; Frailty; Healthcare resources AB BACKGROUND: The purpose of this study was to determine the relationship of frailty and 6-month postoperative costs. METHODS: Subjects aged >= 65 years undergoing elective colorectal operations were enrolled in a prospective observational study. Frailty was assessed by a validated measure of function, cognition, nutrition, comorbidity burden, and geriatric syndromes. Frailty was quantified by summing the number of positive characteristics in each subject. RESULTS: Sixty subjects (mean age, 75 +/- 8 years) were studied. Inpatient mortality was 2% (n = 1). Overall, 40% of subjects (n = 24) were considered nonfrail, 22% (n = 13) were prefrail, and 38% (n = 22) were frail. With advancing frailty, hospital costs increased (P < .001) and costs from discharge to 6-months increased (P < .001). Higher degrees of frailty were related to increased rates of discharge institutionalization (P < .001) and 30-day readmission (P = .044). CONCLUSIONS: A simple, brief preoperative frailty assessment accurately forecasts increased surgical hospital costs and postdischarge to 6-month healthcare costs after colorectal operations in older adults. Published by Elsevier Inc. C1 [Robinson, Thomas N.; Wu, Daniel S.; Stiegmann, Gregory V.] Denver Vet Affairs Med Ctr, Dept Surg, Denver, CO USA. [Robinson, Thomas N.; Wu, Daniel S.; Stiegmann, Gregory V.] Univ Colorado Denver, Hlth Sci Ctr, Dept Surg, Aurora, CO USA. [Moss, Marc] Univ Colorado Denver, Hlth Sci Ctr, Dept Med, Aurora, CO USA. RP Robinson, TN (reprint author), Denver Vet Affairs Med Ctr, Dept Surg, Denver, CO USA. EM thomas.robinson@ucdenver.edu FU NHLBI NIH HHS [K24 HL089223-04, K24 HL089223, K24 HL089223-05, K24-HL-089223]; NIA NIH HHS [K23 AG034632, K23 AG034632-01A1, K23 AG034632-02, K23AG034632] NR 11 TC 70 Z9 71 U1 1 U2 7 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2011 VL 202 IS 5 BP 511 EP 514 DI 10.1016/j.amjsurg.2011.06.017 PG 4 WC Surgery SC Surgery GA 848CJ UT WOS:000297025700005 PM 21890098 ER PT J AU Shepardson, NE Shankar, GM Selkoe, DJ AF Shepardson, Nina E. Shankar, Ganesh M. Selkoe, Dennis J. TI Cholesterol Level and Statin Use in Alzheimer Disease II. Review of Human Trials and Recommendations SO ARCHIVES OF NEUROLOGY LA English DT Review ID COA REDUCTASE INHIBITORS; BLOOD-BRAIN-BARRIER; RANDOMIZED CONTROLLED-TRIAL; LIPID-LOWERING AGENTS; COGNITIVE FUNCTION; INCIDENT DEMENTIA; BETA-PEPTIDE; IN-VIVO; RISK; LOVASTATIN AB Substantial evidence has accumulated in support of the hypothesis that elevated cholesterol levels increase the risk of developing Alzheimer disease (AD). As a result, much work has investigated the potential use of lipid-lowering agents, particularly statins, as preventive or therapeutic agents for AD. Although epidemiology and preclinical statin research (described in part I of this review) have generally supported an adverse role of high cholesterol levels regarding AD, human studies of statins (reviewed herein) show highly variable outcomes, making it difficult to draw firm conclusions. We identify several confounding factors among the human studies, including differing blood-brain barrier permeabilities among statins, the stage in AD at which statins were administered, and the drugs' pleiotropic metabolic effects, all of which contribute to the substantial variability observed to date. We recommend that future human studies of this important therapeutic topic (1) take the blood-brain barrier permeabilities of statins into account when analyzing results, (2) include specific analyses of the effects on low- and high-density lipoprotein cholesterol, and, most important, (3) conduct statin treatment trials solely in patients with mild AD, who have the best chance for disease modification. Arch Neurol. 2011; 68(11): 1385-1392 C1 [Shepardson, Nina E.; Shankar, Ganesh M.; Selkoe, Dennis J.] Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA. [Shepardson, Nina E.; Shankar, Ganesh M.; Selkoe, Dennis J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shankar, Ganesh M.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. RP Selkoe, DJ (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, HIM Room 730,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM dselkoe@rics.bwh.harvard.edu FU National Institutes of Health [AG06173] FX This study was supported by grant AG06173 from the National Institutes of Health (Dr Selkoe). NR 36 TC 74 Z9 75 U1 0 U2 10 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 NOV PY 2011 VL 68 IS 11 BP 1385 EP 1392 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 847ZI UT WOS:000297014900003 PM 22084122 ER PT J AU Khot, S Billings, M Owens, D Longstreth, WT AF Khot, Sandeep Billings, Martha Owens, Darrell Longstreth, W. T., Jr. TI Coping With Death and Dying on a Neurology Inpatient Service Death Rounds as an Educational Initiative for Residents SO ARCHIVES OF NEUROLOGY LA English DT Article ID CARE; PATIENT AB Background: Residents in neurology may feel unprepared to care for dying patients. We developed Death Rounds to provide emotional support and end-of-life care teaching for residents caring for dying patients on the inpatient neurology service. Death Rounds are monthly 1-hour clinical case discussions where residents identify issues through shared experiences. Objective: To survey neurology residents' perceptions of Death Rounds with respect to end-of-life care teaching and emotional support. Design, Setting, and Participants: We conducted an electronic survey of all (n = 26) neurology residents and recent residency graduates at the University of Washington 2 years after instituting monthly Death Rounds. Main Outcome Measure: The survey consisted of 10 questions examining residents' perceptions of the extent to which Death Rounds provided emotional support and end-of-life care teaching. We dichotomized responses to statements about Death Rounds as agree or disagree. Results: All 26 residents responded to the survey and attended at least 1 Death Rounds session. More than half of residents attended more than 3 sessions. Residents agreed that Death Rounds helped them cope with dying patients (17 residents [65%]), delivered closure for the team (16 residents [61%]), and provided emotional support, more for the team (18 residents [69%]) than the individual (10 residents [38%]). Most residents felt that Death Rounds provided useful teaching about end-of-life care (18 residents [69%]), and they were satisfied overall with Death Rounds (16 residents [61%]). Conclusions: Death Rounds afford an opportunity for physicians-in-training to process as a group their feelings, intense emotions, and insecurities while learning from the dying process. In our inpatient neurology service, most residents found it a rewarding and valuable experience. C1 [Khot, Sandeep; Longstreth, W. T., Jr.] Univ Washington, Dept Neurol, Seattle, WA 98104 USA. [Billings, Martha] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Div Pulm & Crit Care Med, Seattle, WA USA. [Owens, Darrell] Univ Washington, Harborview Med Ctr, Palliat Care Serv, Seattle, WA 98104 USA. RP Khot, S (reprint author), Univ Washington, Dept Neurol, 325 9th Ave,Box 359775, Seattle, WA 98104 USA. EM skhot@uw.edu NR 8 TC 10 Z9 10 U1 0 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 NOV PY 2011 VL 68 IS 11 BP 1395 EP 1397 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 847ZI UT WOS:000297014900004 PM 22084123 ER PT J AU Fleisher, AS Chen, KW Liu, XF Roontiva, A Thiyyagura, P Ayutyanont, N Joshi, AD Clark, CM Mintun, MA Pontecorvo, MJ Doraiswamy, PM Johnson, KA Skovronsky, DM Reiman, EM AF Fleisher, Adam S. Chen, Kewei Liu, Xiaofen Roontiva, Auttawut Thiyyagura, Pradeep Ayutyanont, Napatkamon Joshi, Abhinay D. Clark, Christopher M. Mintun, Mark A. Pontecorvo, Michael J. Doraiswamy, P. Murali Johnson, Keith A. Skovronsky, Daniel M. Reiman, Eric M. TI Using Positron Emission Tomography and Florbetapir F 18 to Image Cortical Amyloid in Patients With Mild Cognitive Impairment or Dementia Due to Alzheimer Disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID EPSILON-4 ALLELE; BRAIN; PET; DEPOSITION; DIAGNOSIS; APOE; AGENTS; INDIVIDUALS; POPULATION; STILBENES AB Objectives: To characterize quantitative florbetapir F 18 (hereafter referred to as simply florbetapir) positron emission tomographic (PET) measurements of fibrillar beta-amyloid (A beta) burden in a large clinical cohort of participants with probable Alzheimer disease (AD) or mild cognitive impairment (MCI) and older healthy controls (OHCs). Design: Cerebral-to-whole-cerebellar florbetapir standard uptake value ratios (SUVRs) were computed. Mean cortical SUVRs were compared. A threshold of SUVRs greater than or equal to 1.17 was used to reflect pathological levels of amyloid associated with AD based on separate antemortem PET and postmortem neuropathology data from 19 end-of-life patients. Similarly, a threshold of SUVRs greater than 1.08 was used to signify the presence of any identifiable A beta because this was the upper limit from a separate set of 46 individuals 18 to 40 years of age who did not carry apolipoprotein E (APOE) epsilon 4. Setting: Multiple research imaging centers. Participants: A total of 68 participants with probable AD, 60 participants with MCI, and 82 OHCs who were 55 years of age or older. Main Outcome Measure: Florbetapir-PET activity. Results: All of the participants (ie, those with probable AD or MCI and those who were OHCs) differed significantly in mean (SD) cortical florbetapir SUVRs (1.39 [0.24], 1.17 [0.27], and 1.05 [0.16], respectively; P < 1.0 X 10(-7)), in percentage meeting levels of amyloid associated with AD by SUVR criteria (80.9%, 40.0%, and 20.7%, respectively; P < 1.0 X 10(-7)), and in percentage meeting SUVR criteria for the presence of any identifiable A beta (85.3%, 46.6%, and 28.1%, respectively; P < 1.0 X 10(-7)). Among OHCs, the percentage of florbetapir positivity increased linearly by age decile (P =. 05). For the 54 OHCs with available APOE genotypes, APOE e4 carriers had a higher mean (SD) cortical SUVR than did noncarriers (1.14 [0.2] vs 1.03 [0.16]; P =. 048). Conclusions: The findings of our analysis confirm the ability of florbetapir-PET SUVRs to characterize amyloid levels in clinically probable AD, MCI, and OHC groups using continuous and binary measures of fibrillar A beta burden. It introduces criteria to determine whether an image is associated with an intermediate-to-high likelihood of pathologic AD or with having any identifiable cortical amyloid level above that seen in low-risk young controls. C1 [Fleisher, Adam S.; Chen, Kewei; Liu, Xiaofen; Roontiva, Auttawut; Thiyyagura, Pradeep; Ayutyanont, Napatkamon; Reiman, Eric M.] Univ Arizona, Banner Alzheimers Inst, Coll Med, Phoenix, AZ 85006 USA. [Fleisher, Adam S.; Chen, Kewei; Reiman, Eric M.] Univ Arizona, Arizona Alzheimers Consortium, Coll Med, Phoenix, AZ 85006 USA. [Reiman, Eric M.] Univ Arizona, Dept Psychiat, Coll Med, Phoenix, AZ 85006 USA. [Reiman, Eric M.] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA. [Chen, Kewei] Arizona State Univ, Dept Math, Tempe, AZ 85287 USA. [Fleisher, Adam S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Clark, Christopher M.; Skovronsky, Daniel M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Mintun, Mark A.] Washington Univ, Sch Med, St Louis, MO USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Doraiswamy, P. Murali] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. RP Fleisher, AS (reprint author), Univ Arizona, Banner Alzheimers Inst, Coll Med, 901 E Willetta St, Phoenix, AZ 85006 USA. EM adam.fleisher@bannerhealth.com RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 FU Avid Radiopharmaceuticals; Eli Lilly; Avid; Lundbeck; Medivation; TauRx; Bayer; GE Healthcare; BMS; Astra; Shering; Neuroptix; Neuronetrix; Alzheimer's Foundation; Sonexa; Janssen Alzheimer Immunotherapy FX Dr Fleisher has received research support for nonrelated projects from Avid Radiopharmaceuticals and Eli Lilly and is a consultant for Eli Lilly. Mr Joshi and Drs Clark, Mintun, Pontecorvo, and Skovronsky are employees of Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly. Dr Doraiswamy has received research support or advisory fees from Avid, Lundbeck, Medivation, TauRx, Bayer, GE Healthcare, BMS, Astra, Shering, Neuroptix, Neuronetrix, Alzheimer's Foundation, and Sonexa and owns stock in Sonexa. Dr Johnson has received research support or advisory fees from GE Healthcare, Bayer, Janssen Alzheimer Immunotherapy, and Avid Radiopharmaceuticals. Dr Reiman has received research support for nonrelated projects from Avid Radiopharmaceuticals and Eli Lilly.; This study was supported by funding from Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly. NR 39 TC 129 Z9 133 U1 1 U2 17 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 NOV PY 2011 VL 68 IS 11 BP 1404 EP 1411 DI 10.1001/archneurol.2011.150 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 847ZI UT WOS:000297014900006 PM 21747008 ER PT J AU Jakobiec, FA Kirzhner, M Tollett, MM Mancini, R Hogan, RN AF Jakobiec, Frederick A. Kirzhner, Maria Tollett, Marlene Morales Mancini, Ronald Hogan, R. Nick TI Solitary Epithelioid Histiocytoma (Reticulohistiocytoma) of the Eyelid SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter ID MULTICENTRIC RETICULOHISTIOCYTOSIS C1 [Jakobiec, Frederick A.; Kirzhner, Maria] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Dept Ophthalmol, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Kirzhner, Maria] Harvard Univ, Sch Med, Boston, MA USA. [Tollett, Marlene Morales; Mancini, Ronald; Hogan, R. Nick] Univ Texas SW Med Ctr Dallas, Dept Ophthalmol, Dallas, TX 75390 USA. [Hogan, R. Nick] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Dept Ophthalmol, 243 Charles St,Room 321, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 6 TC 4 Z9 4 U1 0 U2 3 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 NOV PY 2011 VL 129 IS 11 BP 1502 EP 1504 PG 4 WC Ophthalmology SC Ophthalmology GA 848JK UT WOS:000297047600022 PM 22084226 ER PT J AU Wecht, JM Radulovic, M Rosado-Rivera, D Zhang, RL LaFountaine, MF Bauman, WA AF Wecht, Jill M. Radulovic, Miroslav Rosado-Rivera, Dwindally Zhang, Run-Lin LaFountaine, Michael F. Bauman, William A. TI Orthostatic Effects of Midodrine Versus L-NAME on Cerebral Blood Flow and the Renin-Angiotensin-Aldosterone System in Tetraplegia SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Blood pressure; Hypotension; orthostatic; Rehabilitation; Spinal cord injuries ID NITRIC-OXIDE SYNTHASE; SPINAL-CORD-INJURY; SIMULATED MICROGRAVITY; TRANSCRANIAL DOPPLER; MYOCARDIAL-INFARCTION; HYPOTENSION; INHIBITION; PRESSURE; RISK; HYDROCHLORIDE AB Objective: To compare responses to head-up tilt (HUT) in individuals with chronic tetraplegia after midodrine hydrochloride (10mg) versus nitro-L-arginine methyl ester (L-NAME, 1mg/kg) administration. Design: Prospective comparative drug trial. Setting: Veterans Affairs medical center. Participants: Participants (N=7) were studied during 3 laboratory visits: no drug, midodrine (administered orally 30min before HUT), and L-NAME (infused over a 60-min period). Interventions: Anti-hypotensive agents, midodrine, and L-NAME. Main Outcome Measures: Mean arterial pressure (MAP), cerebral blood flow (CBF), and markers of the renin-angiotensin-aldosterone system (RAAS, plasma renin and serum aldosterone) were measured in the supine position at baseline (BL) and during a 45 degrees HUT maneuver. Data were compared between BL and the average of 3 assessments collected during HUT. Results: Orthostatic MAP and CBF were increased with the midodrine and L-NAME groups compared with the no drug trial and the relationship between the change in MAP and CBF was significant (r=0.770; P<0.001). Both L-NAME and midodrine appeared to suppress the post-HUT RAAS response compared with no drug. Conclusions: Increasing orthostatic blood pressure with L-NAME or midodrine appears to increase CBF and suppress the RAAS during HUT in persons with tetraplegia, although more data are needed to confirm these preliminary findings. C1 [Wecht, Jill M.; Radulovic, Miroslav; Rosado-Rivera, Dwindally; Zhang, Run-Lin; LaFountaine, Michael F.; Bauman, William A.] James J Peters VA Med Ctr, Ctr Excellence, Bronx, NY 10468 USA. [Wecht, Jill M.; Radulovic, Miroslav; Bauman, William A.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Wecht, Jill M.; Radulovic, Miroslav; LaFountaine, Michael F.; Bauman, William A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Wecht, Jill M.; Radulovic, Miroslav; Bauman, William A.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. RP Wecht, JM (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM jm.wecht@va.gov FU Veterans Affairs Rehabilitation Research and Development Service [A6161W, B3203R, B4162C] FX Supported by the Veterans Affairs Rehabilitation Research and Development Service (grant nos. A6161W, B3203R, and B4162C). NR 46 TC 7 Z9 7 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2011 VL 92 IS 11 BP 1789 EP 1795 DI 10.1016/j.apmr.2011.03.022 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 846WT UT WOS:000296934600008 PM 21762873 ER PT J AU Karver, MR Weissleder, R Hilderbrand, SA AF Karver, Mark R. Weissleder, Ralph Hilderbrand, Scott A. TI Synthesis and Evaluation of a Series of 1,2,4,5-Tetrazines for Bioorthogonal Conjugation SO BIOCONJUGATE CHEMISTRY LA English DT Article ID INVERSE-ELECTRON-DEMAND; DIELS-ALDER REACTIONS; LIVING CELLS; CLICK CHEMISTRY; CANCER-CELLS; COPPER-FREE; LIGATION; CYCLOADDITIONS; REACTIVITY AB 1,2,4,5-Tetrazines have been established as effective dienes for inverse electron demand [4 + 2] Diels-Alder cycloaddition reactions with strained alkenes for over 50 years. Recently, this reaction pair combination has been applied to bioorthogonal labeling and cell detection applications; however, to date, there has been no detailed examination and optimization of tetrazines for use in biological experiments. Here, we report the synthesis and characterization of 12 conjugatable tetrazines. The tetrazines were all synthesized in a similar fashion and were screened in parallel to identify candidates most ideally suited for biological studies. In depth follow-up studies revealed compounds with varying degrees of stability and reactivity that could each be useful in different bioorthogonal applications. One promising, highly stable, and water-soluble derivative was used in pretargeted cancer cell labeling studies, confirming its utility as a bioorthogonal moiety. C1 [Hilderbrand, Scott A.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Hilderbrand, SA (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St Suite 5-210, Boston, MA 02114 USA. EM scott_hilderbrand@hms.harvard.edu FU NIH [RO1EB010011, P50CA86355] FX The authors would like to thank Dr. Jack Szostak at MGH for the use of the Stopped-Flow spectrophotometer. The authors would also like to thank Alex Chudnovskiy and Elizabeth Tiglao of CSB for technical assistance with cell culture and flow cytometry and Neal K. Devaraj for helpful discussions. This research is supported in part by NIH grants RO1EB010011 and P50CA86355. NR 33 TC 123 Z9 124 U1 2 U2 61 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 NOV PY 2011 VL 22 IS 11 BP 2263 EP 2270 DI 10.1021/bc200295y PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 847VY UT WOS:000297001800009 PM 21950520 ER PT J AU Tannous, BA Teng, J AF Tannous, Bakhos A. Teng, Jian TI Secreted blood reporters: Insights and applications SO BIOTECHNOLOGY ADVANCES LA English DT Review DE Secreted reporter; Gaussia luciferase; SEAP; Soluble peptides; Imaging; Blood assay ID PLACENTAL ALKALINE-PHOSPHATASE; RENILLA-RENIFORMIS LUCIFERASE; OVARIAN-CANCER XENOGRAFTS; TERM GENE-EXPRESSION; IN-VIVO; GAUSSIA LUCIFERASE; MEASLES-VIRUS; FIREFLY LUCIFERASE; PROMOTER ACTIVITY; MAMMALIAN-CELLS AB Secreted reporters detected in body fluids (blood, serum or urine) have shown to be simple and useful tools for ex vivo real-time monitoring of in vivo biological processes. Here we explore the most commonly used secreted blood reporters in experimental animals: secreted alkaline phosphatase, soluble marker peptides derived from human carcinoembryonic antigen and human chorionic gonadotropin, as well as Gaussia luciferase. We also comment on other recently discovered secreted luciferases and their potential use as blood reporters for multiplexing applications. (C) 2011 Elsevier Inc. All rights reserved. C1 [Tannous, Bakhos A.; Teng, Jian] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. [Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Tannous, Bakhos A.; Teng, Jian] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Expt Therapeut & Mol Imaging Lab, Ctr Neurosci, Bldg 149,13th St, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu FU National Institutes of Health; National Cancer Institute [4R00CA126839]; National Institute of Neurological Disorders and Stroke [NS045776, 1R01NS064983] FX Dr. Tannous is supported by grants from the National Institutes of Health, the National Cancer Institute (4R00CA126839) and the National Institute of Neurological Disorders and Stroke (NS045776 and 1R01NS064983). The authors would like to thank Marco Barazas for assistance in drawing Fig. 1. NR 67 TC 20 Z9 20 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0734-9750 J9 BIOTECHNOL ADV JI Biotechnol. Adv. PD NOV-DEC PY 2011 VL 29 IS 6 BP 997 EP 1003 DI 10.1016/j.biotechadv.2011.08.021 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 845KP UT WOS:000296821900041 PM 21920429 ER PT J AU MacDonald, SM Harris, EER Arthur, DW Bailey, L Bellon, JR Carey, L Goyal, S Halyard, MY Moran, MS Horst, KC Haffty, BG AF MacDonald, Shannon M. Harris, Eleanor E. R. Arthur, Douglas W. Bailey, Lisa Bellon, Jennifer R. Carey, Lisa Goyal, Sharad Halyard, Michele Y. Moran, Meena S. Horst, Kathleen C. Haffty, Bruce G. TI ACR Appropriateness Criteria (R) Locally Advanced Breast Cancer SO BREAST JOURNAL LA English DT Article DE appropriateness criteria; breast cancer; locally advanced; radiation ID CONCURRENT RADIATION-THERAPY; COMBINED-MODALITY TREATMENT; NEOADJUVANT CHEMOTHERAPY; STAGE-III; POSTOPERATIVE RADIOTHERAPY; PREOPERATIVE CHEMOTHERAPY; POSTMASTECTOMY RADIATION; COMBINATION CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; REGIONAL RECURRENCE AB Locally advanced breast cancer (LABC) is a disease that is heterogeneous in its presentation, potentially curable, and generally necessitating multidisciplinary management. Radiation therapy (RT) plays an important role in the management of LABC. The integration of radiation with surgery, chemotherapy, and sometimes breast reconstruction can be complex. The American College of Radiology Appropriateness Criteria Breast Committee aims to provide guidance for the management of a variety of LABC cases. The American College of Radiology Appropriateness Criteria is evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is either lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [MacDonald, Shannon M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, Eleanor E. R.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Arthur, Douglas W.] Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. [Bailey, Lisa] Amer Coll Surg, Alta Bates Summit Med Ctr, Oakland, CA USA. [Bellon, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Carey, Lisa] Univ N Carolina Hlth Care Syst, Amer Soc Clin Oncol, Chapel Hill, NC USA. [Goyal, Sharad; Haffty, Bruce G.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Halyard, Michele Y.] Mayo Clin Scottsdale, Scottsdale, AZ USA. [Horst, Kathleen C.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Moran, Meena S.] Yale Univ, Sch Med, New Haven, CT USA. RP MacDonald, SM (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM smacdonald@partners.org OI Harris, Eleanor/0000-0002-7529-7473 NR 70 TC 5 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1075-122X J9 BREAST J JI Breast J. PD NOV-DEC PY 2011 VL 17 IS 6 BP 579 EP 585 DI 10.1111/j.1524-4741.2011.01150.x PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 849DE UT WOS:000297104900003 PM 21906206 ER PT J AU Kopans, D Gavenonis, S Halpern, E Moore, R AF Kopans, Daniel Gavenonis, Sara Halpern, Elkan Moore, Richard TI Calcifications in the Breast and Digital Breast Tomosynthesis SO BREAST JOURNAL LA English DT Article DE breast; calcifications; digital breast tomosynthesis; mammography; screening ID CARCINOMA MORTALITY; MAMMOGRAPHY; NUMBER AB Our study was to compare the clarity with which calcifications are seen on conventional mammography (CM) with the same calcifications on digital breast tomosynthesis (DBT). We define clarity as the sharpness, contrast, and diagnostic quality by which the calcifications were depicted. In a HIPPA compliant Institutional Review Board approved study, 3,000 women volunteered to have both a screening mammogram and a DBT study. A total of 119 sequential cases with relevant calcifications (not clearly benign) were reviewed. Two board certified, dedicated, breast imaging radiologists reviewed the CM and DBT images in an unblinded paired comparison. Only the mediolateral oblique (MLO) projection was available for the DBT studies. The MLO and craniocaudal projections were reviewed using the 2D images. Window and leveling, and electronic zoom were permitted. Unlimited time was allowed to provide a subjective assessment as too how well the calcifications were seen, from a diagnostic perspective, when the two studies were evaluated side-by-side. In 41.6% of the cases, the readers felt that calcifications were seen with superior clarity on DBT. In 50.4% of the cases, the visibility of calcifications was the same for DBT and CM, and in 8% of the cases, calcifications were seen with greater clarity on CM than DBT. In 92% of the cases, the clarity with which calcifications were seen on DBT was equal to or better than for CM and in almost half, the clarity on DBT was judged to be better than for CM. Our analysis shows that calcifications can be demonstrated with equal or greater clarity on DBT as on CM, thus allowing for comparable, and, perhaps, improved interpretive analysis of detected calcifications. C1 [Kopans, Daniel; Gavenonis, Sara; Halpern, Elkan; Moore, Richard] Massachusetts Gen Hosp Radiol, Avon Comprehens Breast Ctr, Boston, MA 02114 USA. RP Kopans, D (reprint author), Massachusetts Gen Hosp Radiol, Avon Comprehens Breast Ctr, Wang ACC 240 15 Parkman St, Boston, MA 02114 USA. EM kopans.daniel@mgh.harvard.edu NR 19 TC 55 Z9 57 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1075-122X J9 BREAST J JI Breast J. PD NOV-DEC PY 2011 VL 17 IS 6 BP 638 EP 644 DI 10.1111/j.1524-4741.2011.01152.x PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 849DE UT WOS:000297104900010 PM 21906207 ER PT J AU Abuabara, K Lee, H Kimball, AB AF Abuabara, K. Lee, H. Kimball, A. B. TI The effect of systemic psoriasis therapies on the incidence of myocardial infarction: a cohort study SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; POSITIVE PREDICTIVE-VALUE; RHEUMATOID-ARTHRITIS; CARDIOVASCULAR-DISEASE; VASCULAR-DISEASES; RISK-FACTORS; CORONARY-ARTERY; DOUBLE-BLIND; MORTALITY; INFLIXIMAB AB Background Psoriasis confers an independent risk of cardiovascular disease that is likely to be related to systemic inflammation. Anti-inflammatory treatment could theoretically reduce the risk of cardiovascular disease, and initial data suggest that treatment may reduce the incidence of cardiovascular risk factors. Objectives To determine the impact of anti-inflammatory therapy on the risk of acute myocardial infarction (MI) in patients with moderate-to-severe psoriasis. Methods Cohort study using administrative and pharmacy claims data from a large U. S. insurer comparing patients with psoriasis aged >= 18 years receiving systemic immunomodulatory therapies (methotrexate, ciclosporin, alefacept, efalizumab, adalimumab, etancercept and infliximab) with a control group treated with ultraviolet B phototherapy that has limited systemic anti-inflammatory effects. The risk of acute MI was calculated using a proportional hazards model while controlling for sex, age, hypertension, hyperlipidaemia, diabetes and depression. Significant interaction terms were included in the final model. Results The study group included 25 554 patients with psoriasis receiving systemic treatment or phototherapy. There was a trend towards an increased risk of MI in the systemic treatment group but not a significant difference in overall MI risk [hazard ratio (HR) 1.33, 95% confidence interval (CI) 0.90-1 96]. Additionally, there was a significant interaction with age: in patients under 50 years the HR for MI if receiving systemic therapy was 0.65 (95% CI 0.32-1.34), and in patients aged 50-70 years it was 1.37 (95% CI 0.79-2.38). Conclusions Overall, there does not appear to be a reduced risk of MI in patients with psoriasis receiving systemic therapy compared with a group undergoing phototherapy. The risk of MI may vary by age. C1 [Kimball, A. B.] Massachusetts Gen Hosp, Dept Dermatol, Clin Unit Res Trials Skin, Boston, MA 02114 USA. [Abuabara, K.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Lee, H.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Clin Unit Res Trials Skin, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU Abbott, Inc.; American Academy of Dermatology; Centocor FX The investigators received a physician-initiated grant from Abbott, Inc. to support this work and to gain access to the UnitedHealth data. The design and conduct of the study, data management, analysis and interpretation, and preparation and approval of the manuscript were all performed independently by the investigators. This work was also funded by the American Academy of Dermatology's Minority Student Mentorship Program.; K.A. and H. L.: none declared. A. B. K.: Investigator and Consultant for Abbott, Centocor and Amgen. She has an outcomes fellowship supported by Centocor. Her department administers phototherapy. NR 49 TC 53 Z9 54 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD NOV PY 2011 VL 165 IS 5 BP 1066 EP 1073 DI 10.1111/j.1365-2133.2011.10525.x PG 8 WC Dermatology SC Dermatology GA 852BG UT WOS:000297318700022 PM 21777216 ER PT J AU Zhang, DF Kearney, CJ Cheriyan, T Schmid, TM Spector, M AF Zhang, Dafang Kearney, Cathal J. Cheriyan, Thomas Schmid, Thomas M. Spector, Myron TI Extracorporeal shockwave-induced expression of lubricin in tendons and septa SO CELL AND TISSUE RESEARCH LA English DT Article DE ESWT; Lubricin; Tendon; Septum; Rat ID SUPERFICIAL ZONE PROTEIN; WAVE THERAPY; GENE-EXPRESSION; ARTICULAR-CARTILAGE; FLEXOR TENDON; BONE; KNEE; PROTEOGLYCAN; CHONDROCYTES; TENDINITIS AB Lubricin, a lubricating glycoprotein that facilitates tendon gliding, is upregulated by mechanical as well as biochemical stimuli, prompting this study of its induction by extracorporeal shockwave therapy (ESWT). The objective of this study was to characterize and quantify the effect of ESWT on lubricin expression in tendons and septa in a rat model. Hindlimbs of six rats were treated with low-dose ESWT and those of another six with high-dose ESWT, using contralateral limbs as controls. After 4 days, resected samples were processed for immunolocalization of lubricin using a purified monoclonal antibody. ESWT was found to increase lubricin expression in both low-dose and high-dose ESWT-treated tendons and also in septa. Lubricin expression generally increased with increasing dose of ESWT. Increased lubricin expression may contribute to the beneficial effects of ESWT in providing pain and symptom relief in musculoskeletal disorders by decreasing erosive wear. C1 [Zhang, Dafang; Kearney, Cathal J.; Cheriyan, Thomas; Spector, Myron] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Zhang, Dafang; Cheriyan, Thomas; Spector, Myron] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Zhang, Dafang; Kearney, Cathal J.; Spector, Myron] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Zhang, Dafang; Cheriyan, Thomas; Spector, Myron] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Schmid, Thomas M.] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Mail Stop 151 Res,150 S Huntington Ave, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu OI Kearney, Cathal/0000-0002-9514-6517 FU Dept. of Veterans Affairs FX This work was supported in part by the Dept. of Veterans Affairs. NR 30 TC 3 Z9 3 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD NOV PY 2011 VL 346 IS 2 BP 255 EP 262 DI 10.1007/s00441-011-1258-7 PG 8 WC Cell Biology SC Cell Biology GA 849JU UT WOS:000297122600011 PM 22009294 ER PT J AU Kullgren, JT Werner, RM AF Kullgren, Jeffrey T. Werner, Rachel M. TI Counterpoint: Will Pubic Reporting of Health-care Quality Measures Inform and Educate Patients? No SO CHEST LA English DT Editorial Material ID OF-CARE; CONSUMERS; NETWORK C1 [Kullgren, Jeffrey T.] Robert Wood Johnson Fdn Clin Scholars, Philadelphia, PA 19104 USA. [Kullgren, Jeffrey T.; Werner, Rachel M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Kullgren, Jeffrey T.; Werner, Rachel M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Univ Penn, Div Gen Internal Med, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Kullgren, JT (reprint author), Robert Wood Johnson Fdn Clin Scholars, 1303B Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM kullgren@mail.med.upenn.edu NR 20 TC 3 Z9 3 U1 2 U2 10 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2011 VL 140 IS 5 BP 1117 EP 1120 DI 10.1378/chest.11-2094 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 846UK UT WOS:000296928500006 PM 22045876 ER PT J AU Kullgren, JT Werner, RM AF Kullgren, Jeffrey T. Werner, Rachel M. TI Counterpoint: Will Pubic Reporting of Health-care Quality Measures Inform and Educate Patients? No Reply SO CHEST LA English DT Editorial Material ID HOSPITALS C1 [Kullgren, Jeffrey T.] Robert Wood Johnson Fdn Clin Scholars, Philadelphia, PA 19104 USA. [Kullgren, Jeffrey T.; Werner, Rachel M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Kullgren, Jeffrey T.; Werner, Rachel M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Univ Penn, Perelman Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Kullgren, JT (reprint author), Robert Wood Johnson Fdn Clin Scholars, 1303B Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM kullgren@mail.med.upenn.med NR 7 TC 0 Z9 0 U1 1 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2011 VL 140 IS 5 BP 1121 EP 1122 DI 10.1378/chest.11-2095 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 846UK UT WOS:000296928500008 ER PT J AU Krodel, DJ Bittner, EA Abdulnour, REE Brown, RH Eikermann, M AF Krodel, David J. Bittner, Edward A. Abdulnour, Raja-Elie E. Brown, Robert H. Eikermann, Matthias TI Negative Pressure Pulmonary Edema Following Bronchospasm SO CHEST LA English DT Article ID ASTHMA AB Negative pressure pulmonary edema (NPPE) is an important cause of noncardiogenic pulmonary edema but is rarely reported in the setting of bronchospasm. A 43-year-old woman with severe reactive airway disease suffered an episode of severe bronchospasm after endotracheal extubation following an otherwise uneventful general anesthetic. Subsequently, she developed clinical and radiographic signs of pulmonary edema in the absence of other symptoms of acute left-sided heart failure, leading to the diagnosis of noncardiogenic pulmonary edema. She received noninvasive positive pressure ventilation for a few hours, after which her clinical and radiologic signs and symptoms of pulmonary edema were greatly improved. This clinical scenario strongly suggests NPPE. We submit that it is possible to create NPPE by generating highly negative intrathoracic pressures in the setting of severe bronchospasm. CHEST 2011; 140(5):1351-1354 C1 [Krodel, David J.; Bittner, Edward A.; Eikermann, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Abdulnour, Raja-Elie E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA 02114 USA. [Brown, Robert H.] Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD USA. [Brown, Robert H.] Johns Hopkins Univ, Dept Environm Hlth Sci, Div Physiol, Baltimore, MD 21205 USA. [Brown, Robert H.] Johns Hopkins Univ, Dept Med, Div Pulm Med, Baltimore, MD USA. [Brown, Robert H.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. RP Krodel, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM dkrodel@partners.org NR 5 TC 4 Z9 5 U1 1 U2 8 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2011 VL 140 IS 5 BP 1351 EP 1354 DI 10.1378/chest.11-0529 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 846UK UT WOS:000296928500038 PM 22045880 ER PT J AU O'Connor, CM Fiuzat, M Lombardi, C Fujita, K Jia, G Davison, BA Cleland, J Bloomfield, D Dittrich, HC DeLucca, P Givertz, MM Mansoor, G Ponikowski, P Teerlink, JR Voors, AA Massie, BM Cotter, G Metra, M AF O'Connor, Christopher M. Fiuzat, Mona Lombardi, Carlo Fujita, Kenji Jia, Gang Davison, Beth A. Cleland, John Bloomfield, Daniel Dittrich, Howard C. DeLucca, Paul Givertz, Michael M. Mansoor, George Ponikowski, Piotr Teerlink, John R. Voors, Adriaan A. Massie, Barry M. Cotter, Gad Metra, Marco TI Impact of Serial Troponin Release on Outcomes in Patients With Acute Heart Failure Analysis From the PROTECT Pilot Study SO CIRCULATION-HEART FAILURE LA English DT Article DE cardiac troponin; acute heart failure; rolofylline ID IN-HOSPITAL MORTALITY; LONG-TERM PROGNOSIS; CARDIAC TROPONIN; AMBULATORY PATIENTS; ADENOSINE A(1); OPTIMIZE-HF; TASK-FORCE; ASSOCIATION; DYSFUNCTION; GUIDELINES AB Background-Cardiac troponin T (cTnT) elevation is common and is a predictor of outcomes in patients with acute heart failure (AHF). The degree and progression of cTnT release during hospitalization of patients with AHF is unclear. We evaluated the incidence of cTnT release during AHF hospitalization and the relationship of cTnT release with outcomes. Methods and Results-The Placebo-controlled Randomized study of the selective A(1) adenosine receptor antagonist rolofylline for patients hospitalized with acute heart failure and volume Overload to assess Treatment Effect on Congestion and renal funcTion (PROTECT) pilot study was a multicenter, double-blind study of patients with AHF. Measurements of cTnT were collected at randomization and days 2, 3, 4, and 7. Patients were classified on the basis of their serum cTnT levels at baseline: positive (>0.03 ng/mL), detectable (>0.01 ng/mL), and negative (>= 0.01 ng/mL). A detectable cTnT level developed during the study (after baseline) was classified as cTnT conversion: 288 patients were included; 172 (60%) patients had detectable cTnT levels and 97 (34%) had positive values (>0.03 ng/mL) at baseline. Of the 116 patients with negative troponin at baseline, 24 (21%) had elevated cTnT levels by day 7. On multivariable analysis, positive cTnT at baseline was an independent predictor of the composite end point of cardiovascular/renal rehospitalization or death at 60 days (hazard ratio, 1.84; 95% confidence interval, 1.04-3.26; P=0.036). Kaplan-Meier curves showed similar worse outcomes in patients with troponin conversion and positive troponin at baseline. Conclusions-There was a high prevalence of baseline cTnT elevation in this cohort; 21% of those negative at baseline converted to detectable levels by day 7. Positive troponin at baseline, and conversion to positive levels, were associated with worse outcomes at 60 days. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00328692 and NCT00354458. (Circ Heart Fail. 2011;4:724-732.) C1 [O'Connor, Christopher M.; Fiuzat, Mona] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Lombardi, Carlo; Metra, Marco] Univ Brescia, Dept Expt & Appl Med, Brescia, Italy. [Fujita, Kenji; Jia, Gang; Bloomfield, Daniel; Dittrich, Howard C.; DeLucca, Paul; Mansoor, George] Merck Res Labs, Rahway, NJ USA. [Davison, Beth A.; Cotter, Gad] Momentum Res, Durham, NC USA. [Cleland, John] Univ Hull, Kingston Upon Hull HU6 7RX, N Humberside, England. [Givertz, Michael M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Teerlink, John R.; Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.; Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. RP O'Connor, CM (reprint author), DUMC Box 3356, Durham, NC 27705 USA. EM oconn002@mc.duke.edu RI Teerlink, John/D-2986-2012; lombardi, carlo /O-2130-2013; Ponikowski, Piotr/O-6454-2015; OI lombardi, carlo /0000-0002-7120-5877; Ponikowski, Piotr/0000-0002-3391-7064; Davison, Beth/0000-0003-2374-6449; Cleland, John/0000-0002-1471-7016; Metra, Marco/0000-0001-6691-8568 FU Merck FX Drs O'Connor, Voors, Ponikowski, Dittrich, Metra, Teerlink, Massie, Givertz, Cleland, Weatherley, and Cotter received research funding from Merck. Drs Jia, Fujita, Mansoor, Bloomfield, and DeLucca are employees of Merck. NR 32 TC 39 Z9 40 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD NOV PY 2011 VL 4 IS 6 BP 724 EP 732 DI 10.1161/CIRCHEARTFAILURE.111.961581 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 850AF UT WOS:000297166100012 PM 21900185 ER PT J AU Ge, XW Wu, L Hu, WG Fernandes, S Wang, C Li, X Brown, JR Qin, XB AF Ge, Xiaowen Wu, Lin Hu, Weiguo Fernandes, Stacey Wang, Chun Li, Xu Brown, Jennifer R. Qin, Xuebin TI rILYd4, a Human CD59 Inhibitor, Enhances Complement-Dependent Cytotoxicity of Ofatumumab against Rituximab-Resistant B-cell Lymphoma Cells and Chronic Lymphocytic Leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID ANTI-CD20 MONOCLONAL-ANTIBODY; MEMBRANE ATTACK COMPLEX; NON-HODGKIN LYMPHOMAS; REGULATORY PROTEINS; IN-VITRO; AUTOIMMUNE DISORDERS; PROTECTIN CD59; CANCER-CELLS; HUMAN CD20; ACTIVATION AB Purpose: Ofatumumab is an anti-CD20 antibody recently approved for treatment of fludarabine and alemtuzumab refractory chronic lymphocytic leukemia (CLL); it mediates much stronger complement-dependent cytotoxicity (CDC) than rituximab. Human CD59, a key membrane complement regulator that inhibits CDC, is highly expressed in B-cell malignancies and its upregulation is an important determinant of the sensitivity of B-cell malignancies to rituximab treatment. Previously, we have shown that the potent CD59 inhibitor rILYd4 sensitizes rituximab-resistant lymphoma cells to rituximab-mediated CDC. Here, we further investigated whether rILYd4 can sensitize B-cell malignancies to ofatumumab-mediated CDC and whether either ofatumumab-mediated CDC or rILYd4-enhanced ofatumumab-mediated CDC correlates with CD20 or CD59 expression, known biomarkers involved in rituximab activity. Experimental Design: Rituximab-resistant cell lines and primary CLL cells were used to investigate the antitumor efficacy of the combination of rILYd4 with ofatumumab or rituximab. Propidium iodide staining or alamarBlue assay were used to evaluate the CDC effect. The levels of CD20 and CD59 on the cell membrane were analyzed by flow cytometry. Results: rILYd4 enhanced CDC effects mediated by ofatumumab or rituximab on rituximab-resistant lymphoma cells and primary CLL cells in vitro. The sensitivity to CDC effects mediated by ofatumumab positively correlated with the ratio of CD20/CD59 and negatively correlated with CD59 levels on CLL cells. The degree to which rILYd4 enhanced CDC correlated positively with the CD59 levels on CLL cells. Conclusions: These data suggest that rILYd4 may enhance the anticancer activity of ofatumumab and rituximab in B-cell malignancies that have relapsed after prior antibody-based therapies. Clin Cancer Res; 17(21); 6702-11. (C)2011 AACR. C1 [Ge, Xiaowen; Wu, Lin; Hu, Weiguo; Qin, Xuebin] Harvard Univ, Sch Med, Lab Translat Res, Cambridge, MA 02139 USA. [Ge, Xiaowen; Li, Xu] Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 1, Ctr Mol Med, Xian, Peoples R China. [Hu, Weiguo; Brown, Jennifer R.; Qin, Xuebin] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA USA. [Fernandes, Stacey; Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wu, Lin; Wang, Chun] Shanghai First Peoples Hosp, Dept Hematol, Shanghai, Peoples R China. RP Qin, XB (reprint author), Harvard Univ, Sch Med, Lab Translat Res, 1 Kendall Sq,Bldg 600,3rd Floor, Cambridge, MA 02139 USA. EM xuebin_qin@hms.harvard.edu FU GSK; Harvard Technology Development Accelerator Fund; China Scholarship Council [2009628090]; ASH; Leukemia and Lymphoma Society; [NIHRO1AI061174]; [NIHR21CA141324]; [NIHK23CA115682] FX J.R. Brown receives research funding from GSK. No potential conflicts of interest were disclosed by the other authors.; This work was supported by NIHRO1AI061174 (to X. B. Qin) and NIHR21CA141324 (to X. B. Qin), Harvard Technology Development Accelerator Fund (to X. B. Qin), and China Scholarship Council (2009628090; to X. Ge). J.R. Brown is supported by NIHK23CA115682 as well as by an ASH Scholar award and the Leukemia and Lymphoma Society Scholar in Clinical Research Award. NR 46 TC 25 Z9 26 U1 0 U2 8 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 NOV 1 PY 2011 VL 17 IS 21 BP 6702 EP 6711 DI 10.1158/1078-0432.CCR-11-0647 PG 10 WC Oncology SC Oncology GA 842TS UT WOS:000296624000014 PM 21918174 ER PT J AU Ouillette, P Collins, R Shakhan, S Li, JH Li, C Shedden, K Malek, SN AF Ouillette, Peter Collins, Roxane Shakhan, Sajid Li, Jinghui Li, Cheng Shedden, Kerby Malek, Sami N. TI The Prognostic Significance of Various 13q14 Deletions in Chronic Lymphocytic Leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; CHROMOSOME 13Q14; GENOMIC COMPLEXITY; TRANSCRIPTION MAP; GENE; REGION; CLL; LOCUS; SEQUENCE; SURVIVAL AB Purpose: To further our understanding of the biology and prognostic significance of various chromosomal 13q14 deletions in chronic lymphocytic leukemia (CLL). Experimental Design: We analyzed data from SNP 6.0 arrays to define the anatomy of various 13q14 deletions in a cohort of 255 CLL patients and have correlated two subsets of 13q14 deletions (type I exclusive of RB1 and type II inclusive of RB1) with patient survival. Furthermore, we measured the expression of the 13q14-resident microRNAs by quantitative PCR (Q-PCR) in 242 CLL patients and subsequently assessed their prognostic significance. We sequenced all coding exons of RB1 in patients with monoallelic RB1 deletion and have sequenced the 13q14-resident miR locus in all patients. Results: Large 13q14 (type II) deletions were detected in approximately 20% of all CLL patients and were associated with shortened survival. A strong association between 13q14 type II deletions and elevated genomic complexity, as measured through CLL-FISH or SNP 6.0 array profiling, was identified, suggesting that these lesions may contribute to CLL disease evolution through genomic destabilization. Sequence and copy number analysis of the RB1 gene identified a small CLL subset that is RB1 null. Finally, neither the expression levels of the 13q14-resident microRNAs nor the degree of 13q14 deletion, as measured through SNP 6.0 array-based copy number analysis, had significant prognostic importance. Conclusions: Our data suggest that the clinical course of CLL is accelerated in patients with large (type II) 13q14 deletions that span the RB1 gene, therefore justifying routine identification of 13q14 subtypes in CLL management. Clin Cancer Res; 17(21); 6778-90. (C)2011 AACR. C1 [Ouillette, Peter; Collins, Roxane; Shakhan, Sajid; Li, Jinghui; Malek, Sami N.] Univ Michigan, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA. [Shedden, Kerby] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Li, Cheng] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Malek, SN (reprint author), Univ Michigan, Dept Internal Med, Div Hematol & Oncol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM smalek@med.umich.edu FU NIH [1R01 CA136537-01]; Leukemia and Lymphoma Society of America; NIH through the University of Michigan [5 P30 CA46592] FX This work was supported by the NIH through grant 1R01 CA136537-01 (to S.N. Malek), the Translational Research Program of the Leukemia and Lymphoma Society of America (to S.N. Malek), and a Scholar in Clinical Research Award from the Leukemia and Lymphoma Society of America (to S.N. Malek). This research is supported (in part) by the NIH through the University of Michigan's Cancer Center Support grant (5 P30 CA46592). NR 39 TC 44 Z9 45 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2011 VL 17 IS 21 BP 6778 EP 6790 DI 10.1158/1078-0432.CCR-11-0785 PG 13 WC Oncology SC Oncology GA 842TS UT WOS:000296624000021 PM 21890456 ER PT J AU Mayer, EL Baurain, JF Sparano, J Strauss, L Campone, M Fumoleau, P Rugo, H Awada, A Sy, O Llombart-Cussac, A AF Mayer, Erica L. Baurain, Jean-Francois Sparano, Joseph Strauss, Lewis Campone, Mario Fumoleau, Pierre Rugo, Hope Awada, Ahmad Sy, Oumar Llombart-Cussac, Antonio TI A Phase 2 Trial of Dasatinib in Patients with Advanced HER2-Positive and/or Hormone Receptor-Positive Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID TYROSINE KINASE-ACTIVITY; C-SRC; SOLID TUMORS; INHIBITS GROWTH; CELL-LINES; METASTASIS; EXPRESSION; SURVIVAL; TAMOXIFEN; BONE AB Purpose: SRC-family kinases (SFK) are involved in numerous oncogenic signaling pathways. A phase 2 trial of dasatinib, a potent oral tyrosine kinase inhibitor of SFKs, was carried out in patients with human epidermal growth factor receptor 2-positive (HER2+) and/or hormone receptor-positive (HR+) advanced breast cancer. Experimental Design: Patients with measurable tumors and progression after chemotherapy and HER2 and/or HR-targeted agents in adjuvant or metastatic settings (maximum of two prior metastatic setting regimens) received twice daily dasatinib. Primary endpoint was Response Evaluation Criteria in Solid Tumors-defined response rate. Secondary endpoints included toxicity and limited pharmacokinetics. Results: Seventy patients (55 years median age) were treated, 83% of HER2+ patients had received prior HER2-directed therapy, and 61% of HR+ patients had received prior endocrine therapy in the advanced setting. Dasatinib starting dose was reduced from 100 to 70 mg twice daily to limit toxicity. Median therapy duration was 1.8 months in both dose groups and most discontinuations were due to progression. Of 69 evaluable patients, three had confirmed partial responses and six had stable disease for 16 weeks or more (disease control rate 13.0%); all nine of these tumors were HR+ (two were also HER2+). The most common drug-related toxicities were gastrointestinal complaints, headache, asthenia, and pleural effusion. Grade 3-4 toxicity occurred in 37% of patients and was comparable between doses; drug-related serious adverse events were less frequent with 70 mg twice daily than 100 mg twice daily. Conclusion: Limited single-agent activity was observed with dasatinib in patients with advanced HR+ breast cancer. Clin Cancer Res; 17(21); 6897-904. (C)2011 AACR. C1 [Mayer, Erica L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Awada, Ahmad] Inst Jules Bordet, B-1000 Brussels, Belgium. [Sparano, Joseph] Montefiore Einstein Canc Ctr, New York, NY USA. [Strauss, Lewis; Sy, Oumar] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Campone, Mario] Ctr Lutte Canc Nantes Atlantique, St Herblain, France. [Fumoleau, Pierre] Ctr Georges Francois Leclerc, Dijon, France. [Rugo, Hope] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Llombart-Cussac, Antonio] Hosp Arnau Vilanova, Lleida, Spain. RP Mayer, EL (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Erica_Mayer@dfci.harvard.edu RI Llombart-Cussac, Antonio/A-6706-2010 FU Bristol-Myers Squibb Oncology, Princeton, NJ; Bristol-Myers Squibb FX This study was sponsored by Bristol-Myers Squibb Oncology, Princeton, NJ.; This study was designed by employees of Bristol-Myers Squibb with input from investigators. Patient data were collected at participating institutes, analyzed using the data-management systems of the sponsor, and interpreted by the statistical team of the sponsor in collaboration with the authors. Study data were available to all authors. An initial version of the manuscript was written by Erica Mayer, and further developed with assistance from an independent company funded by Bristol-Myers Squibb. All authors contributed to writing and reviewing of the manuscript and agreed with the decision to submit for publication. NR 32 TC 41 Z9 43 U1 0 U2 9 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 NOV 1 PY 2011 VL 17 IS 21 BP 6897 EP 6904 DI 10.1158/1078-0432.CCR-11-0070 PG 8 WC Oncology SC Oncology GA 842TS UT WOS:000296624000033 PM 21903773 ER PT J AU Stedman, MR Gagnon, DR Lew, RA Jung, SH Losina, E Brookhart, MA AF Stedman, Margaret R. Gagnon, David R. Lew, Robert A. Jung, Sin-Ho Losina, Elena Brookhart, M. Alan TI A SAS macro for a clustered logrank test SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE Logrank test; Cluster randomized trial; Clustered logrank test; SAS macro ID SURVIVAL-DATA; RANK-TESTS AB The clustered logrank test is a nonparametric method of significance testing for correlated survival data. Examples of its application include cluster randomized trials where groups of patients rather than individuals are randomized to either a treatment or a control intervention. We describe a SAS macro that implements the 2-sample clustered logrank test for data where the entire cluster is randomized to the same treatment group. We discuss the theory and applications behind this test as well as details of the SAS code. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Stedman, Margaret R.; Losina, Elena] Brigham & Womens Hosp, Orthoped & Arthrit Ctr Outcomes Res, Dept Orthoped, Boston, MA 02115 USA. [Gagnon, David R.; Lew, Robert A.; Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Gagnon, David R.; Lew, Robert A.] Boston VA Healthcare Syst, MAVERIC, VA Cooperat Studies, Boston, MA USA. [Stedman, Margaret R.; Losina, Elena] Harvard Univ, Sch Med, Boston, MA USA. [Jung, Sin-Ho] Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC USA. [Brookhart, M. Alan] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. RP Stedman, MR (reprint author), Brigham & Womens Hosp, Orthoped & Arthrit Ctr Outcomes Res, Dept Orthoped, 75 Francis St, Boston, MA 02115 USA. EM mstedman2@partners.org OI Gagnon, David/0000-0002-6367-3179; Stedman, Margaret/0000-0001-9271-8332 FU National Institutes of Health [AG-027400]; [NRSA/T32 AR055885-03] FX I would like to acknowledge Dr. Daniel H. Solomon at Harvard Medical School and Brigham and Women's Hospital for his osteoporosis studies which provided inspiration for this work. This research was supported by the National Institutes of Health, Grant #AG-027400 awarded to M. Alan Brookhart and NRSA/T32 AR055885-03 awarded to Margaret Stedman. NR 8 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD NOV PY 2011 VL 104 IS 2 BP 266 EP 270 DI 10.1016/j.cmpb.2011.02.001 PG 5 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 847AU UT WOS:000296945100031 PM 21496938 ER PT J AU Hamrah, P Alipour, F Jiang, S Sohn, JH Foulks, GN AF Hamrah, P. Alipour, F. Jiang, S. Sohn, J-H Foulks, G. N. TI Optimizing evaluation of Lissamine Green parameters for ocular surface staining SO EYE LA English DT Article DE Lissamine Green; corneal staining; dry eye; ocular surface; conjunctiva; vital dye ID EYE WORKSHOP 2007; DRY EYE; ROSE-BENGAL; IN-VITRO; SUBCOMMITTEE; CORNEAL; DISEASE; TESTS AB Purpose The recently published seminal dry eye workshop proceedings defined Lissamine Green (LG), an organic dye, as a gold standard for demonstrating ocular surface staining. The purpose of the current study was to determine the optimal parameters of 1% LG instillation for the ocular surface examination in dry eye patients. Design Prospective and observational quality improvement study. Methods A quality improvement study evaluated 16 eyes from eight dry eye patients with different levels of severity. LG (1%), in three volumes (5, 10, and 20 mu l) was instilled into the conjunctival cul-de-sac, and four masked observers with different levels of clinical expertise examined the patients with and without red filter. The staining pattern of the conjunctiva and cornea was documented with the Oxford scale within 4 min of LG instillation. Optimal volume and inter-observer reliability were assessed. Results All dye volumes were tolerated well by all patients. Experienced observers preferred 10 mu l volume because of the ease of examination and accuracy. Although instillation of 20 mu l yielded similar scores as 10 mu l, it resulted in overflow of the lid and facial skin staining. The use of red filter significantly improved reading scores (P<0.01). Inter-observer reliability was higher for conjunctival scores than for corneal scores for all patients. The highest reliability was demonstrated with 10 mu l volume and increased with greater experience of the observer. Conclusions Ocular surface examination with instillation of 10 mu l 1% LG has good inter-observer reliability and is well tolerated. Observation through a red filter facilitates the examination. Eye (2011) 25, 1429-1434; doi:10.1038/eye.2011.184; published online 12 August 2011 C1 [Hamrah, P.; Jiang, S.; Sohn, J-H; Foulks, G. N.] Univ Louisville, Dept Ophthalmol & Visual Sci, Louisville, KY 40292 USA. [Hamrah, P.; Alipour, F.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & Refract Surg Serv,Dept Ophthalmol, Boston, MA USA. RP Foulks, GN (reprint author), Univ Louisville, Dept Ophthalmol & Visual Sci, Louisville, KY 40292 USA. EM gnfoul01@louisville.edu FU NIH [K08-EY020575]; New England Corneal Transplant Research Fund; RPB Department FX Financial support was provided by NIH K08-EY020575 (PH), New England Corneal Transplant Research Fund (PH) and RPB Department Grant (GF). NR 20 TC 8 Z9 9 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD NOV PY 2011 VL 25 IS 11 BP 1429 EP 1434 DI 10.1038/eye.2011.184 PG 6 WC Ophthalmology SC Ophthalmology GA 850PY UT WOS:000297209400006 PM 21836630 ER PT J AU Jurkunas, UV Jakobiec, FA Shin, J Zakka, FR Michaud, N Jethva, R AF Jurkunas, U. V. Jakobiec, F. A. Shin, J. Zakka, F. R. Michaud, N. Jethva, R. TI Reversible corneal epitheliopathy caused by vitamin B12 and folate deficiency in a vegan with a genetic mutation: a new disease SO EYE LA English DT Letter C1 [Jurkunas, U. V.; Jakobiec, F. A.; Shin, J.; Zakka, F. R.; Michaud, N.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Jurkunas, U. V.] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Cogan Lab Ophthalm Pathol, Dept Ophthalmol, Boston, MA USA. [Jethva, R.] Floating Hosp Children, Tufts Med Ctr, Boston, MA USA. RP Jurkunas, UV (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. EM Ula_Jurkunas@meei.harvard.edu FU NEI NIH HHS [R01 EY020581, R01EY020581] NR 5 TC 1 Z9 1 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD NOV PY 2011 VL 25 IS 11 BP 1512 EP 1514 DI 10.1038/eye.2011.177 PG 3 WC Ophthalmology SC Ophthalmology GA 850PY UT WOS:000297209400018 PM 21818128 ER PT J AU Bhattacharya, A Jernigan, AL Sabia, M Zhang, YQ Li, Y Qi, WB Van Remmen, H AF Bhattacharya, Arunabh Jernigan, Amanda L. Sabia, Marian Zhang, Yiqiang Li, Yan Qi, Wenbo Van Remmen, Holly TI Disruption of the 12/15-Lipoxygenase Gene (Alox15) Protects Against Denervation-Induced Muscle Atrophy SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 18th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 16-20, 2011 CL Atlanta, GA SP Soc Free Rad Biol & Med (SFRBM) C1 [Bhattacharya, Arunabh; Jernigan, Amanda L.; Sabia, Marian; Zhang, Yiqiang; Li, Yan; Qi, Wenbo; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst, San Antonio, TX 78229 USA. [Van Remmen, Holly] S Texas Vet Hlth Care Syst, San Antonio, TX 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2011 VL 51 SU 1 BP S76 EP S76 DI 10.1016/j.freeradbiomed.2011.10.420 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 848FS UT WOS:000297036600186 ER PT J AU Kachadourian, R Day, BJ Pugazhenti, S Franklin, CC Mahaffey, G Gauthier, C Valdameri, G Di Pietro, A Boumendjel, A AF Kachadourian, Remy Day, Brian J. Pugazhenti, Subbiah Franklin, Christopher C. Mahaffey, Gregory Gauthier, Charlotte Valdameri, Glaucio Di Pietro, Attilio Boumendjel, Ahcene TI A New Synthetic Chalcone Derivative is a Potent Inducer of Glutathione Synthesis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 18th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 16-20, 2011 CL Atlanta, GA SP Soc Free Rad Biol & Med (SFRBM) C1 [Kachadourian, Remy; Day, Brian J.; Pugazhenti, Subbiah; Franklin, Christopher C.] Univ Colorado Denver, Denver, CO USA. [Pugazhenti, Subbiah; Mahaffey, Gregory] Denver VA Med Ctr, Denver, CO USA. [Gauthier, Charlotte; Valdameri, Glaucio; Di Pietro, Attilio] CNRS, Inst Biol & Chim Prot, Lyon, France. [Boumendjel, Ahcene] Univ Grenoble 1, Grenoble, France. RI Valdameri, Glaucio/A-8909-2013 OI Valdameri, Glaucio/0000-0003-1882-1512 NR 2 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2011 VL 51 SU 1 BP S88 EP S89 DI 10.1016/j.freeradbiomed.2011.10.407 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 848FS UT WOS:000297036600221 ER PT J AU Mostoslavsky, R AF Mostoslavsky, Raul TI SIRT6, A MASTER REGULATOR OF GLUCOSE HOMEOSTASIS AND CANCER METABOLISM SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 18th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 16-20, 2011 CL Atlanta, GA SP Soc Free Rad Biol & Med (SFRBM) C1 [Mostoslavsky, Raul] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2011 VL 51 SU 1 BP S8 EP S8 DI 10.1016/j.freeradbiomed.2011.10.017 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 848FS UT WOS:000297036600014 ER PT J AU Shi, Y Liu, YH Li, Y Hamilton, RT Jernigan, AL Jang, YC Van Remmen, H AF Shi, Yun Liu, Yuhong Li, Yan Hamilton, Ryan T. Jernigan, Amanda L. Jang, Youngmok C. Van Remmen, Holly TI Age-related Changes in Neurotrophic Factors Expression in Skeletal Muscle Undergoing Atrophy SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 18th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 16-20, 2011 CL Atlanta, GA SP Soc Free Rad Biol & Med (SFRBM) C1 [Shi, Yun; Liu, Yuhong; Li, Yan; Hamilton, Ryan T.; Jernigan, Amanda L.; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Jang, Youngmok C.] Harvard Univ, Cambridge, MA 02138 USA. [Van Remmen, Holly] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2011 VL 51 SU 1 BP S79 EP S80 DI 10.1016/j.freeradbiomed.2011.10.431 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 848FS UT WOS:000297036600197 ER PT J AU Boudreaux, ED Niro, K Sullivan, A Rosenbaum, CD Allen, M Camargo, CA AF Boudreaux, Edwin D. Niro, Kathryn Sullivan, Ashley Rosenbaum, Christopher D. Allen, Michael Camargo, Carlos A., Jr. TI Current practices for mental health follow-up after psychiatric emergency department/psychiatric emergency service visits: a national survey of academic emergency departments SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Emergency; Psychiatry; Follow-up; Referral; Outpatient ID USERS; TEAM; CARE AB Objective: The objective was to describe continuity of care approaches for psychiatric emergencies in the emergency department. Methods: A national survey of all 138 academic emergency departments in the United States was conducted. Results: Most emergency physicians (81%) had no systematic method for identifying psychiatric emergency patients with high recidivism. In order to promote outpatient care, sites commonly reported using intensive interventions, including scheduling outpatient appointments prior to discharge (72%) and in-house case management (64%). Conclusion: While systematic identification of repeat psychiatric emergency patients was uncommon, emergency departments reported using a variety of fairly intensive strategies to promote continuity of care with outpatient mental health services. (C) 2011 Elsevier Inc. All rights reserved. C1 [Boudreaux, Edwin D.; Rosenbaum, Christopher D.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA 01655 USA. [Niro, Kathryn; Sullivan, Ashley; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Emergency Med Network, Boston, MA 02114 USA. [Allen, Michael] Univ Colorado, Depress Ctr, Aurora, CO 80045 USA. RP Rosenbaum, CD (reprint author), Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA 01655 USA. EM edwin.boudreaux@umassmed.edu; kniro@partners.org; afsullivan@partners.org; Christopher.Rosenbaum@umassmemorial.org; michael.allen@ucdenver.edu; ccamargo@partners.org RI McCarthy, Jodie/B-5760-2012; Allen, Michael/A-8776-2011; OI Boudreaux, Edwin/0000-0002-3223-6371 NR 25 TC 6 Z9 6 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2011 VL 33 IS 6 BP 631 EP 633 DI 10.1016/j.genhosppsych.2011.05.020 PG 3 WC Psychiatry SC Psychiatry GA 848EU UT WOS:000297034000015 PM 21872940 ER PT J AU Dupuy, JM Ostacher, MJ Huffman, J Perlis, RH Nierenberg, AA AF Dupuy, Jamie M. Ostacher, Michael J. Huffman, Jeffrey Perlis, Roy H. Nierenberg, Andrew A. TI A critical review of pharmacotherapy for major depressive disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Review DE Antidepressant; major depressive disorder; outcomes; pharmacological treatment ID SEROTONIN REUPTAKE INHIBITORS; STAR-ASTERISK-D; PLACEBO-CONTROLLED-TRIAL; ANTIDEPRESSANT PRESCRIPTION RATES; RESISTANT UNIPOLAR DEPRESSION; DOUBLE-BLIND; 2ND-GENERATION ANTIDEPRESSANTS; MODAFINIL AUGMENTATION; ADJUNCTIVE TREATMENT; RESIDUAL SYMPTOMS AB Newer generation antidepressant drugs, with improvements in safety and tolerability, have replaced tricyclic antidepressants as first-line treatment of depressive illness. However, no single antidepressant drug from any class has distinguished itself as the obvious first-line treatment of major depression. The choice of therapy is driven primarily by patient choice, with informed consent for the risks of adverse effects. Cost has become an additional factor in this decision as several of the newer antidepressant drugs are now available in generic form. Several augmentation and drug-switching strategies have demonstrated benefit in refractory illness. While no single strategy distinguished itself as superior to the others, some have been more rigorously tested. Ongoing efforts at improving effectiveness, time to response, and tolerability have led to novel drug therapies. Efforts at characterizing predictors of treatment outcomes now include pharmacogenetic studies. C1 [Dupuy, Jamie M.; Huffman, Jeffrey; Perlis, Roy H.; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA. [Dupuy, Jamie M.; Huffman, Jeffrey; Perlis, Roy H.; Nierenberg, Andrew A.] Harvard Univ, Sch Med, Boston, MA USA. [Ostacher, Michael J.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA USA. RP Dupuy, JM (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, Dept Psychiat, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM jdupuy@partners.org OI Ostacher, Michael/0000-0003-0353-7535 FU National Institute on Alcoholism and Alcohol Abuse [K23AA016340-01A1]; Harvard Catalyst/The Harvard Clinical and Translational Science Center [UL1 RR 025758]; Harvard University; Pfizer; AstraZeneca; Bristol-Myers Squibb; Eli Lilly Company; GlaxoSmithKline; Janssen Pharmaceutica; Massachusetts General Psychiatry Academy; Eli Lilly Co.; Proteus Biomedical; Concordant Rater Systems; MGH from NIMH; PamLabs; Pfizer Pharmaceuticals; Shire; Eli Lilly; Janssen Pharmaceuticals FX Supported in part by the National Institute on Alcoholism and Alcohol Abuse (Grant K23AA016340-01A1), and the Scholars in Clinical Science Program of Harvard Catalyst/The Harvard Clinical and Translational Science Center (Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centres) (Dr Ostacher). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centres, the National Center for Research Resources or the National Institutes of Health.; Dr Ostacher has received research support from Pfizer, and has served on the advisory/consulting boards of Pfizer, Schering-Plough, and Concordant Rater Systems. He has received speaker's fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Janssen Pharmaceutica, Pfizer, and Massachusetts General Psychiatry Academy.; Dr Perlis has received honoraria, consulting, or speaker's fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., GlaxoSmithKline, Pfizer, Proteus Biomedical, and Concordant Rater Systems. He holds patents and receives royalties with Concordant Rater Systems.; Dr Nierenberg is a full-time employee of the Massachusetts General Hospital (MGH). In the past 12 months (as of 3 March 2009), he has served as a consultant to the American Psychiatric Association (only travel expenses paid), Appliance Computing Inc. (Mindsite), Brandeis University. Through the MGH Clinical Trials Network and Institute, he has consulted for Brain Cells, Inc., Dianippon Sumitomo/Sepracor Novartis, PGx Health, Shire, Schering-Plough, Targacept, and Takeda/Lundbeck Pharmaceuticals. He received grant/research support through MGH from NIMH, PamLabs, Pfizer Pharmaceuticals, and Shire. He received honoraria from Belvior Publishing, University of Texas Southwestern Dallas, Hillside Hospital, American Drug Utilization Review, American Society for Clinical Psychopharmacology, Baystate Medical Center, Columbia University, IMEDEX, MJ Consulting, New York State, MBL Publishing, Physicians Postgraduate Press, SUNY Buffalo, University of Wisconsin, and the University of Pisa. Dr Nierenberg is a presenter for the Massachusetts General Hospital Psychiatry Academy (MGHPA). The education programs conducted by the MGHPA were supported through Independent Medical Education (IME) grants from the following pharmaceutical companies in 2008: Astra Zeneca, Eli Lilly, and Janssen Pharmaceuticals; in 2009 Astra Zeneca, Eli Lilly, and Bristol-Myers Squibb. No speakers' bureaus or boards since 2003. He is on the advisory boards of Appliance Computing, Inc., Brain Cells, Inc., Eli Lilly and Company, and Takeda/Lundbeck and Targacept. Dr. Nierenberg owns stock options in Appliance Computing, Inc. and Brain Cells, Inc. Through MGH, he is named for copyrights to the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery-Asberg Depression Scale exclusively licensed to the MGH Clinical Trials Network and Institute (CTNI). Also, through MGH, Dr Nierenberg has a patent extension application for the combination of buspirone, bupropion, and melatonin for the treatment of depression. NR 93 TC 10 Z9 12 U1 1 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD NOV PY 2011 VL 14 IS 10 BP 1417 EP 1431 DI 10.1017/S1461145711000083 PG 15 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 849DO UT WOS:000297106000012 PM 21349226 ER PT J AU Vogt, D Vaughn, R Glickman, ME Schultz, M Drainoni, ML Elwy, R Eisen, S AF Vogt, Dawne Vaughn, Rachel Glickman, Mark E. Schultz, Mark Drainoni, Mari-Lynn Elwy, Rani Eisen, Susan TI Gender Differences in Combat-Related Stressors and Their Association With Postdeployment Mental Health in a Nationally Representative Sample of US OEF/OIF Veterans SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE gender; veterans; military personnel; trauma exposure; mental health ID ARMED-FORCES PERSONNEL; MALE VIETNAM VETERANS; WAR-ZONE STRESSORS; RISK-FACTORS; SEX-DIFFERENCES; IRAQ WAR; RESILIENCE INVENTORY; MILITARY PERSONNEL; DEPLOYMENT RISK; UK MILITARY AB Though the broader literature suggests that women may be more vulnerable to the effects of trauma exposure, most available studies on combat trauma have relied on samples in which women's combat exposure is limited and analyses that do not directly address gender differences in associations between combat exposure and postdeployment mental health. Female service members' increased exposure to combat in Afghanistan and Iraq provides a unique opportunity to evaluate gender differences in different dimensions of combat-related stress and associated consequence for postdeployment mental health. The current study addressed these research questions in a representative sample of female and male U. S. veterans who had returned from deployment to Afghanistan or Iraq within the previous year. As expected, women reported slightly less exposure than men to most combat-related stressors, but higher exposure to other stressors (i.e., prior life stress, deployment sexual harassment). No gender differences were observed in reports of perceived threat in the war zone. Though it was hypothesized that combat-related stressors would demonstrate stronger negative associations with postdeployment mental health for women, only one of 16 stressor X gender interactions achieved statistical significance and an evaluation of the clinical significance of these interactions revealed that effects were trivial. Results suggest that female Operation Enduring Freedom/Operation Iraqi Freedom service members may be as resilient to combat-related stress as men. Future research is needed to evaluate gender differences in the longer-term effects of combat exposure. C1 [Vogt, Dawne] Boston Univ, Sch Med, Natl Ctr PTSD, Div Psychiat, Boston, MA 02130 USA. [Vogt, Dawne; Vaughn, Rachel] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [Glickman, Mark E.; Schultz, Mark; Drainoni, Mari-Lynn; Elwy, Rani; Eisen, Susan] Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Glickman, Mark E.; Drainoni, Mari-Lynn; Elwy, Rani; Eisen, Susan] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02130 USA. RP Vogt, D (reprint author), Boston Univ, Sch Med, Natl Ctr PTSD, Div Psychiat, 150 S Huntington Ave,116-3, Boston, MA 02130 USA. EM Dawne.Vogt@va.gov OI Glickman, Mark/0000-0003-3993-2801 NR 51 TC 79 Z9 79 U1 1 U2 12 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 NOV PY 2011 VL 120 IS 4 BP 797 EP 806 DI 10.1037/a0023452 PG 10 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 847XT UT WOS:000297009400003 PM 21639595 ER PT J AU Vogt, D Smith, B Elwy, R Martin, J Schultz, M Drainoni, ML Eisen, S AF Vogt, Dawne Smith, Brian Elwy, Rani Martin, James Schultz, Mark Drainoni, Mari-Lynn Eisen, Susan TI Predeployment, Deployment, and Postdeployment Risk Factors for Posttraumatic Stress Symptomatology in Female and Male OEF/OIF Veterans SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE trauma exposure; risk factors; posttraumatic stress disorder; conservation of resources theory; Veterans ID MALE VIETNAM VETERANS; WAR-ZONE STRESSORS; SOCIAL SUPPORT; LIFE EVENTS; PSYCHOMETRIC PROPERTIES; RESILIENCE INVENTORY; NATIONAL SAMPLE; PTSD CHECKLIST; FIT INDEXES; DISORDER AB Prior research on risk factors for posttraumatic stress symptomatology (PTSS) in war-exposed Veterans has revealed both direct and indirect mechanisms of risk that span predeployment, deployment, and postdeployment timeframes. The aims of the present study were to identify the mechanisms through which previously documented risk factors contribute to PTSS in a national sample of 579 female and male Veterans deployed to Afghanistan for Operation Enduring Freedom (OEF) or to Iraq for Operation Iraqi Freedom (OIF), as well as to examine the extent to which results mirror associations observed among Vietnam Veterans (King, King, Foy, Keane, & Fairbank, 1999). Consistent with conservation of resources (COR) theory (Hobfoll, 1989, 2001), findings indicated that PTSS is accounted for by multiple chains of risk, many originating in predeployment experiences that place Veterans at risk for additional stress exposure, and foretell difficulty accessing resources in the face of subsequent stressors. Importantly, the majority of previously documented mechanisms were replicated in this study, suggesting key pathways through which risk factors may contribute to PTSS across different Veteran populations. Results also revealed a number of novel risk mechanisms for OEF/OIF female Veterans, particularly with respect to the role of deployment family relationships in risk for PTSS. C1 [Vogt, Dawne; Smith, Brian] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Vogt, Dawne; Smith, Brian] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Elwy, Rani; Schultz, Mark; Drainoni, Mari-Lynn; Eisen, Susan] Edith Nourse Rogers Mem Vet Hosp, CHQOER, Bedford, MA USA. [Martin, James] Bryn Mawr Coll, Grad Sch Social Work & Social Res, Bryn Mawr, PA 19010 USA. [Drainoni, Mari-Lynn] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Drainoni, Mari-Lynn] Boston Univ, Sch Med, Dept Med, Infect Dis Sect, Boston, MA 02118 USA. RP Vogt, D (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 116B-3,150 S Huntington Ave, Boston, MA 02130 USA. EM Dawne.Vogt@va.gov RI Schueter, nicos/A-3625-2014 NR 63 TC 50 Z9 50 U1 2 U2 9 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 NOV PY 2011 VL 120 IS 4 BP 819 EP 831 DI 10.1037/a0024457 PG 13 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 847XT UT WOS:000297009400005 PM 21707125 ER PT J AU Lo Celso, C Scadden, DT AF Lo Celso, Cristina Scadden, David T. TI The haematopoietic stem cell niche at a glance SO JOURNAL OF CELL SCIENCE LA English DT Editorial Material ID BONE-MARROW NICHE; PROGENITOR CELLS; IN-VIVO; SELF-RENEWAL; ENDOTHELIAL-CELLS; OSTEOBLASTIC NICHE; ENDOSTEAL NICHE; BETA-CATENIN; TGF-BETA; MICROENVIRONMENT C1 [Lo Celso, Cristina] Univ London Imperial Coll Sci Technol & Med, Div Cell & Mol Biol, London SW7 2AZ, England. [Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Scadden, David T.] Harvard Univ, Dept Stem Cells & Regenerat Biol, Cambridge, MA 02138 USA. RP Lo Celso, C (reprint author), Univ London Imperial Coll Sci Technol & Med, Div Cell & Mol Biol, Sir Alexander Fleming Bldg,S Kensington Campus, London SW7 2AZ, England. EM clocelso@imperial.ac.uk OI Lo Celso, Cristina/0000-0002-1163-4207 FU Biotechnology and Biological Sciences Research Council [BB/I004033/1]; Cancer Research UK [CEA C36195/A11831]; NHLBI NIH HHS [HL044851, HL097748, HL097794, HL100402, R01 HL044851, R01 HL097748, R01 HL097794, U01 HL100402] NR 92 TC 56 Z9 57 U1 0 U2 14 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV 1 PY 2011 VL 124 IS 21 BP 3529 EP 3535 DI 10.1242/jcs.074112 PG 7 WC Cell Biology SC Cell Biology GA 847LV UT WOS:000296975300002 PM 22083139 ER PT J AU Alston, TA AF Alston, Theodore A. TI Precipitation of sugammadex by protamine SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Letter ID REVERSAL AGENT C1 [Alston, Theodore A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Alston, Theodore A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Alston, TA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM alstoncorbett@comcast.net NR 2 TC 2 Z9 2 U1 0 U2 3 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 NOV PY 2011 VL 23 IS 7 BP 593 EP 593 DI 10.1016/j.jclinane.2011.04.004 PG 1 WC Anesthesiology SC Anesthesiology GA 848FJ UT WOS:000297035600020 PM 22050813 ER PT J AU Goldwasser, J Cohen, PY Lin, WY Kitsberg, D Balaguer, P Polyak, SJ Chung, RT Yarmush, ML Nahmias, Y AF Goldwasser, Jonathan Cohen, Pazit Y. Lin, Wenyu Kitsberg, Danny Balaguer, Patrick Polyak, Stephen J. Chung, Raymond T. Yarmush, Martin L. Nahmias, Yaakov TI Naringenin inhibits the assembly and long-term production of infectious hepatitis C virus particles through a PPAR-mediated mechanism SO JOURNAL OF HEPATOLOGY LA English DT Article DE HCV; Naringenin; Lipid metabolism; PPAR alpha ID TRIGLYCERIDE TRANSFER PROTEIN; LOW-DENSITY; FLAVONOID NARINGENIN; CITRUS FLAVONOIDS; RNA REPLICATION; CELL-LINES; IN-VITRO; SECRETION; EXPRESSION; RESISTANCE AB Background & Aims: Hepatitis C virus (HCV) infection affects 3% of the world population and is the leading cause of chronic liver disease worldwide. Current standard of care is effective in only 50% of the patients, poorly tolerated, and associated with significant side effects and viral resistance. Recently, our group and others demonstrated that the HCV lifecycle is critically dependent on host lipid metabolism and that its production is metabolically modulated. Methods: The JFH1/Huh7.5.1 full lifecycle model of HCV was used to study the antiviral effects of naringenin on viral replication, assembly, and production. Activation of PPAR alpha was elucidated using GAL4-PPAR alpha fusion reporters, PPRE reporters, qRT-PCR, and metabolic studies. Metabolic results were confirmed in primary human hepatocytes. Results: We demonstrate that the grapefruit flavonoid naringenin dose-dependently inhibits HCV production without affecting intracellular levels of the viral RNA or protein. We show that naringenin blocks the assembly of intracellular infectious viral particles, upstream of viral egress. This antiviral effect is mediated in part by the activation of PPARa, leading to a decrease in VLDL production without causing hepatic lipid accumulation in Huh7.5.1 cells and primary human hepatocytes. Long-term treatment with naringenin leads to a rapid 1.4 log reduction in HCV, similar to 1000 U of interferon. During the washout period, HCV levels returned to normal, consistent with our proposed mechanism of action. Conclusions: The data demonstrates that naringenin is a nontoxic assembly inhibitor of HCV and that other PPARa agonists play a similar role in blocking viral production. The combination of naringenin with STAT-C agents could potentially bring a rapid reduction in HCV levels during the early treatment phase, an outcome associated with sustained virological response. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Cohen, Pazit Y.; Kitsberg, Danny; Nahmias, Yaakov] Hebrew Univ Jerusalem, Selim & Rachel Benin Sch Engn, Jerusalem, Israel. [Goldwasser, Jonathan; Yarmush, Martin L.; Nahmias, Yaakov] Shriners Burns Hosp, Ctr Engn Med, Boston, MA USA. [Goldwasser, Jonathan] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. [Goldwasser, Jonathan; Lin, Wenyu; Chung, Raymond T.; Yarmush, Martin L.; Nahmias, Yaakov] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Balaguer, Patrick] Univ Montpellier 1, INSERM, Montpellier, France. [Polyak, Stephen J.] Univ Washington, Seattle, WA 98195 USA. RP Nahmias, Y (reprint author), Hebrew Univ Jerusalem, Selim & Rachel Benin Sch Engn, Jerusalem, Israel. EM ynahmias@gmail.com RI Nahmias, Yaakov/H-4725-2013; Balaguer, Patrick/I-2973-2016; OI Nahmias, Yaakov/0000-0002-6051-616X FU National Institute of Diabetes and Digestive and Kidney Diseases [K01DK080241]; Harvard Clinical Nutrition Research Center [P30-DK040561]; European Research Council [TMIHCV 242699]; BioMEMS Resource Center [P41EB-002503]; Alexander Silberman Institute of Life Sciences FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K01DK080241) and the Harvard Clinical Nutrition Research Center (P30-DK040561). Resources were provided by European Research Council Starting Grant (TMIHCV 242699), the BioMEMS Resource Center (P41EB-002503), and the Alexander Silberman Institute of Life Sciences. NR 43 TC 42 Z9 43 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD NOV PY 2011 VL 55 IS 5 BP 963 EP 971 DI 10.1016/j.jhep.2011.02.011 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 846BN UT WOS:000296872300005 PM 21354229 ER PT J AU Nadazdin, O Boskovic, S Wee, SL Sogawa, H Koyama, I Colvin, RB Smith, RN Tocco, G O'Connor, DH Karl, JA Madsen, JC Sachs, DH Kawai, T Cosimi, AB Benichou, G AF Nadazdin, Ognjenka Boskovic, Svjetlan Wee, Siew-Lin Sogawa, Hiroshi Koyama, Ichiro Colvin, Robert B. Smith, R. Neal Tocco, Georges O'Connor, David H. Karl, Julie A. Madsen, Joren C. Sachs, David H. Kawai, Tatsuo Cosimi, A. Benedict Benichou, Gilles TI Contributions of Direct and Indirect Alloresponses to Chronic Rejection of Kidney Allografts in Nonhuman Primates SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MEMORY T-CELLS; PERSISTENT ALLOPEPTIDE REACTIVITY; CLASS-II PEPTIDES; INDIRECT RECOGNITION; INDIRECT ALLORECOGNITION; MHC PEPTIDES; HOMEOSTATIC PROLIFERATION; TRANSPLANT RECIPIENTS; HETEROLOGOUS IMMUNITY; REGULATORY TOLERANCE AB The relative contribution of direct and indirect allorecognition pathways to chronic rejection of allogeneic organ transplants in primates remains unclear. In this study, we evaluated T and B cell alloresponses in cynomolgus monkeys that had received combined kidney/bone marrow allografts and myeloablative immunosuppressive treatments. We measured donor-specific direct and indirect T cell responses and alloantibody production in monkeys (n = 5) that did not reject their transplant acutely but developed chronic humoral rejection (CHR) and in tolerant recipients (n = 4) that never displayed signs of CHR. All CHR recipients exhibited high levels of anti-donor Abs and mounted potent direct T cell alloresponses in vitro. Such direct alloreactivity could be detected for more than 1 y after transplantation. In contrast, only two of five monkeys with CHR had a detectable indirect alloresponse. No indirect alloresponse by T cells and no alloantibody responses were found in any of the tolerant monkeys. Only one of four tolerant monkeys displayed a direct T cell alloresponse. These observations indicate that direct T cell alloresponses can be sustained for prolonged periods posttransplantation and result in alloantibody production and chronic rejection of kidney transplants, even in the absence of detectable indirect alloreactivity. The Journal of Immunology, 2011, 187: 4589-4597. C1 [Benichou, Gilles] Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Transplant Ctr, Boston, MA 02114 USA. [Nadazdin, Ognjenka; Boskovic, Svjetlan; Wee, Siew-Lin; Sogawa, Hiroshi; Koyama, Ichiro; Colvin, Robert B.; Smith, R. Neal; Tocco, Georges; Madsen, Joren C.; Sachs, David H.; Kawai, Tatsuo; Cosimi, A. Benedict; Benichou, Gilles] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Colvin, Robert B.; Smith, R. Neal] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [O'Connor, David H.; Karl, Julie A.] Univ Wisconsin, Dept Pathol & Lab Med, Wisconsin Natl Primate Res Ctr, Madison, WI 53711 USA. RP Benichou, G (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Transplant Ctr, 55 Fruit St,Thier 807, Boston, MA 02114 USA. EM gbenichou@partners.org OI o'connor, david/0000-0003-2139-470X FU Massachusetts General Hospital Executive Committee on Research; National Institute of Allergy and Infectious Diseases [U19 AI066705, PO1HL18646, RO1HL093131]; National Institutes of Health [19 DK080652, HL018446] FX This work was supported by Massachusetts General Hospital Executive Committee on Research, National Institute of Allergy and Infectious Diseases Grants U19 AI066705 (to G. B.) and PO1HL18646 and RO1HL093131 (to J.C.M.), and National Institutes of Health Grants 19 DK080652 and HL018446 (to A.B.C.). NR 54 TC 6 Z9 6 U1 2 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2011 VL 187 IS 9 BP 4589 EP 4597 DI 10.4049/jimmunol.1003253 PG 9 WC Immunology SC Immunology GA 841ET UT WOS:000296496000025 PM 21957140 ER PT J AU Xiang, M Shi, XL Li, YH Xu, J Yin, LH Xiao, GZ Scott, MJ Billiar, TR Wilson, MA Fan, J AF Xiang, Meng Shi, Xiaolian Li, Yuehua Xu, Jia Yin, Lianhua Xiao, Guozhi Scott, Melanie J. Billiar, Timothy R. Wilson, Mark A. Fan, Jie TI Hemorrhagic Shock Activation of NLRP3 Inflammasome in Lung Endothelial Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MOBILITY GROUP BOX-1; INTERLEUKIN-1 RECEPTOR ANTAGONIST; RESPIRATORY-DISTRESS-SYNDROME; NEUTROPHIL NADPH OXIDASE; MULTIPLE ORGAN FAILURE; SEVERE BLUNT TRAUMA; TLR2 UP-REGULATION; NAD(P)H OXIDASE; ISCHEMIA/REPERFUSION INJURY; ALVEOLAR MACROPHAGES AB Hemorrhagic shock (HS) due to major trauma and surgery predisposes the host to the development of systemic inflammatory response syndrome (SIRS), including acute lung injury (ALI), through activating and exaggerating the innate immune response. IL-1 beta is a crucial proinflammatory cytokine that contributes to the development of SIRS and ALI. Lung endothelial cells (EC) are one important source of IL-1 beta, and the production of active IL-1 beta is controlled by the inflammasome. In this study, we addressed the mechanism underlying HS activation of the inflammasome in lung EC. We show that high mobility group box 1 acting through TLR4, and a synergistic collaboration with TLR2 and receptor for advanced glycation end products signaling, mediates HS-induced activation of EC NAD(P) H oxidase. In turn, reactive oxygen species derived from NAD(P) H oxidase promote the association of thioredoxin-interacting protein with the nucleotide-binding oligomerization domain-like receptor protein NLRP3 and subsequently induce inflammasome activation and IL-1 beta secretion from the EC. We also show that neutrophil-derived reactive oxygen species play a role in enhancing EC NAD(P) H oxidase activation and therefore an amplified inflammasome activation in response to HS. The present study explores a novel mechanism underlying HS activation of EC inflammasome and thus presents a potential therapeutic target for SIRS and ALI induced after HS. The Journal of Immunology, 2011, 187: 4809-4817. C1 [Fan, Jie] Vet Affairs Pittsburgh Healthcare Syst, Dept Surg, Res & Dev, Pittsburgh, PA 15240 USA. [Xiang, Meng; Shi, Xiaolian; Li, Yuehua; Xu, Jia; Scott, Melanie J.; Billiar, Timothy R.; Wilson, Mark A.; Fan, Jie] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15213 USA. [Xiang, Meng; Yin, Lianhua] Fudan Univ, Shanghai Med Coll, Dept Physiol & Pathophysiol, Shanghai 200032, Peoples R China. [Shi, Xiaolian] Xi An Jiao Tong Univ, Coll Med, Dept Pharmacol, Xian 710061, Peoples R China. [Xu, Jia] So Med Univ, Dept Pathophysiol, Guangzhou 510515, Guangdong, Peoples R China. [Xiao, Guozhi] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. RP Fan, J (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Dept Surg, Res & Dev, Bldg 1,Room 2W109 151L-U,Univ Dr C, Pittsburgh, PA 15240 USA. EM jif7@pitt.edu FU National Institutes of Health [R01-HL-079669]; National Institutes of Health Center [P50-GM-53789]; Veterans Administration FX This work was supported by National Institutes of Health Grant R01-HL-079669 (to J.F. and M.A.W.), National Institutes of Health Center Grant P50-GM-53789 (to T.R.B. and J.F.), and a Veterans Administration Merit Award (to J.F.). NR 61 TC 52 Z9 59 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2011 VL 187 IS 9 BP 4809 EP 4817 DI 10.4049/jimmunol.1102093 PG 9 WC Immunology SC Immunology GA 841ET UT WOS:000296496000046 PM 21940680 ER PT J AU Spires-Jones, TL Kopeikina, KJ Koffie, RM de Calignon, A Hyman, BT AF Spires-Jones, Tara L. Kopeikina, Katherine J. Koffie, Robert M. de Calignon, Alix Hyman, Bradley T. TI Are Tangles as Toxic as They Look? SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Tau; Alzheimer; Neurofibrillary tangle; Neurodegeneration ID ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; HYPERPHOSPHORYLATED-TAU; TRANSGENIC MICE; NEURONAL LOSS; ENDOPLASMIC-RETICULUM; CASPASE ACTIVATION; AXONAL-TRANSPORT; ENDOGENOUS-TAU; REPEAT DOMAIN AB Neurofibrillary tangles are intracellular accumulations of hyperphosphorylated and misfolded tau protein characteristic of Alzheimer's disease and other tauopathies. Classic cross-sectional studies of Alzheimer patient brains showed associations of tangle accumulation with neuronal loss, synapse loss, and dementia, which led to the supposition that tangles are toxic to neurons. More recent advances in imaging techniques and mouse models have allowed the direct exploration of the question of toxicity of aggregated versus soluble tau and have surprisingly challenged the view of tangles as toxic species in the brain. Here, we review these recent experiments on the nature of the toxicity of tau with particular emphasis on our experiments imaging tangles in the intact brain through a cranial window, which allows observation of tangle formation and longitudinal imaging of the fate of tangle-bearing neurons. C1 [Spires-Jones, Tara L.; Kopeikina, Katherine J.; Koffie, Robert M.; Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. [Kopeikina, Katherine J.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [de Calignon, Alix] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England. RP Spires-Jones, TL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 114 16th St, Boston, MA 02129 USA. EM tspires@partners.org; bhyman@partners.org OI Spires-Jones, Tara/0000-0003-2530-0598 FU National Institute of Health [AG08487, T32AG000278, AG026249, K99AG33670]; Alzheimer's Association FX This work was supported by National Institute of Health grants AG08487, T32AG000278, AG026249, K99AG33670 and the Alzheimer's Association Zenith Award. NR 64 TC 40 Z9 40 U1 2 U2 12 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2011 VL 45 IS 3 SI SI BP 438 EP 444 DI 10.1007/s12031-011-9566-7 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 841NL UT WOS:000296518900020 PM 21638071 ER PT J AU Dickerson, BC AF Dickerson, Bradford C. TI Quantitating Severity and Progression in Primary Progressive Aphasia SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Magnetic resonance imaging; Cerebral cortex; Primary progressive aphasia; Frontotemporal dementia; Clinical trials; Biomarkers ID FRONTOTEMPORAL LOBAR DEGENERATION; ALZHEIMERS-DISEASE; SEMANTIC DEMENTIA; SYMPTOM SEVERITY; PICKS-DISEASE; 3 VARIANTS; PATHOLOGY; DISORDERS; SIGNATURE; DIAGNOSIS AB Primary progressive aphasia (PPA) is an insidiously progressive clinical syndrome that includes at its core an impairment in language. From a clinical perspective, there are a variety of diagnostic challenges; international consensus has only recently been reached on the nomenclature for specific clinical subtypes. There are at present no established treatments, and efforts to develop treatments have been hampered by the lack of standardized methods to monitor progression of the illness. This is further complicated by the multiplicity of underlying neuropathologies. Although measures developed from work with stroke aphasia and from work with disorders such as Alzheimer's disease and frontotemporal dementia have provided a valuable foundation for monitoring progression, PPA presents unique challenges to clinicians aiming to quantify impairments for the purposes of full characterization and monitoring, and ultimately with the goal of designing clinical trials of interventions to make a meaningful difference in patients' lives. In this review, I will summarize the main points made in my presentation at the 2010 International Conference on Frontotemporal Dementia, expand from there to summarize our current approach to monitoring progression of PPA, and finally will outline some ideas about goals for the development of better tools for this purpose. C1 MGH Frontotemporal Dementia Unit, Charlestown, MA 02129 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol,Frontotemporal Dementia Unit, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Psychiat,Frontotemporal Dementia Unit, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA. RP Dickerson, BC (reprint author), MGH Frontotemporal Dementia Unit, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu FU NIA [R01-AG29411, R21-AG29840, P50-AG005134]; Alzheimer's Association FX This work was supported by grants from the NIA R01-AG29411, R21-AG29840, P50-AG005134, and the Alzheimer's Association. We express special appreciation to the participants in our program and their families for their valuable contributions. The author thanks Daisy Sapolsky, MS, CCC-SLP for her dedicated collaborative partnership in these efforts. The author reports no disclosures. NR 46 TC 7 Z9 8 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2011 VL 45 IS 3 SI SI BP 618 EP 628 DI 10.1007/s12031-011-9534-2 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 841NL UT WOS:000296518900039 PM 21573887 ER PT J AU Penrod, JD Luhrs, CA Livote, EE Cortez, TB Kwak, J AF Penrod, Joan D. Luhrs, Carol A. Livote, Elayne E. Cortez, Therese B. Kwak, Jennifer TI Implementation and Evaluation of a Network-Based Pilot Program to Improve Palliative Care in the Intensive Care Unit SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Palliative care; critical care; intensive care unit; ICU; quality improvement AB Background. Intensive care unit (ICU) care could be improved by implementation of time-triggered evidence-based interventions including identification of a patient/family medical decision maker, the patient's advance directive status, and cardiopulmonary resuscitation preferences by Day 1; offer of social work and spiritual support by Day 3; and a family meeting establishing goals of care by Day 5. We implemented a program to improve care for ICU patients in five Department of Veterans Affairs' ICUs. Measures. We measured the percent of ICU patients with lengths of stay of five or more days that received the care processes by the appropriate day. Intervention. Critical care and palliative care providers trained ICU nurse teams to improve care through auditing, performance feedback, improvement tools, education, and monthly team meetings. Outcomes. Pre- and postintervention care were compared. Offering social work and spiritual support, identification of the medical decision maker, and documentation of family meetings significantly improved. Conclusions/Lessons Learned. ICU nurse teams can be engaged to improve care under the aegis of a collaborative quality improvement project. J Pain Symptom Manage 2011;42:668-671. Published by Elsevier Inc. on behalf of U.S. Cancer Pain Relief Committee. C1 [Penrod, Joan D.; Livote, Elayne E.; Kwak, Jennifer] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Luhrs, Carol A.; Cortez, Therese B.] VA New York Harbor Healthcare Syst, Brooklyn, NY USA. RP Penrod, JD (reprint author), James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM joan.penrod@mssm.edu FU Department of Veterans Affairs; Health Services Research; Development Service FX This work was supported in part by the Department of Veterans Affairs, Health Services Research and Development Service. The authors declare no conflicts of interest. NR 5 TC 12 Z9 13 U1 0 U2 7 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 NOV PY 2011 VL 42 IS 5 BP 668 EP 671 DI 10.1016/j.jpainsymman.2011.06.012 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 847YL UT WOS:000297011800005 PM 22045370 ER PT J AU Villarreal, D Restrepo, MI Healy, J Howard, B Tidwell, J Ross, J Hartronft, S Jawad, M Sanchez-Reilly, S Reed, K Espinoza, SE AF Villarreal, Deborah Restrepo, Marcos I. Healy, Jennifer Howard, Bonita Tidwell, Janet Ross, Jeanette Hartronft, Scotte Jawad, Marriyam Sanchez-Reilly, Sandra Reed, Kristin Espinoza, Sara E. TI A Model for Increasing Palliative Care in the Intensive Care Unit: Enhancing Interprofessional Consultation Rates and Communication SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Palliative care; critical care; end of life; quality improvement; interprofessional ID OUTCOMES; STATES AB Background. Only a minority of patients who die in the medical intensive care unit (MICU) receive palliative care services. At the South Texas Veterans Health Care System Audie L. Murphy Hospital, only 5% of patients who died in the MICU from May to August 2010 received a palliative care consultation. Measures. We measured the percentage of MICU patients for which there was a palliative care consultation during the intervention period. Intervention. Starting October 1, 2010 and ending April 30, 2011, the palliative care and MICU teams participated in daily "pre-rounds'' to identify patients at risk for poor outcomes, who may benefit from a palliative care consultation. Outcomes. Palliative care consultation increased significantly from 5% to 59% for patients who died in the MICU during the intervention period. Additionally, palliative care consultation increased from 5% to 21% for all patients admitted to the MICU during the intervention period. Conclusions/Lessons Learned. Daily pre-rounds between the palliative care and MICU teams increased palliative care services for MICU patients at risk for poor outcomes, who may benefit from a palliative care consultation. J Pain Symptom Manage 2011;42:676-679. Published by Elsevier Inc. on behalf of U.S. Cancer Pain Relief Committee. C1 [Villarreal, Deborah] Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, Div Geriatr Gerontol & Palliat Med, San Antonio, TX 78229 USA. [Villarreal, Deborah; Healy, Jennifer; Ross, Jeanette; Jawad, Marriyam; Sanchez-Reilly, Sandra; Espinoza, Sara E.] Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr Gerontol & Palliat Med, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care, San Antonio, TX 78229 USA. [Jawad, Marriyam] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, San Antonio, TX 78229 USA. RP Villarreal, D (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, Div Geriatr Gerontol & Palliat Med, 7400 Merton Minter, San Antonio, TX 78229 USA. EM villarreald4@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 FU U.S. Department of Health and Human Services, Health Resources and Services Administration, Bureau of Health Professions FX Dr. Villareal is receiving career development support from the U.S. Department of Health and Human Services, Health Resources and Services Administration, Bureau of Health Professions, Geriatric Academic Career Award. NR 9 TC 9 Z9 9 U1 1 U2 5 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 NOV PY 2011 VL 42 IS 5 BP 676 EP 679 DI 10.1016/j.jpainsymman.2011.07.004 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 847YL UT WOS:000297011800007 PM 22045372 ER PT J AU Vig, EK Sudore, RL Berg, KM Fromme, EK Arnold, RM AF Vig, Elizabeth K. Sudore, Rebecca L. Berg, Karina M. Fromme, Erik K. Arnold, Robert M. TI Responding to Surrogate Requests That Seem Inconsistent With a Patient's Living Will SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Surrogates; decision making; advance directives; substituted judgment ID LIFE DECISION-MAKING; SUSTAINING TREATMENT; PREFERENCES; CHOICES; INTERESTS; JUDGMENTS; STABILITY; DISAGREE; OTHERS; FAMILY AB Clinicians may feel conflicted when a patient's legal decision maker is making decisions that seem inconsistent with a patient's living will. We provide evidence-based information to help clinicians consider whether a surrogate's inconsistent decisions are ethically appropriate. Surrogates are not flawless translators of their loved one's preferences; they are influenced by their own hopes and the current clinical context. Patients may be aware of this, are often concerned about burdening their loved ones, and often grant their surrogates leeway in interpreting their wishes. When appropriate, clinicians should respect surrogates' interpretations of patient values and take steps to decrease surrogate stress during the decision-making process. Finally, if clinicians are cognizant of their own values and preferences, they may recognize how these may affect their responses to certain clinical cases. J Pain Symptom Manage 2011;42:777-782. (C) 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Vig, Elizabeth K.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Vig, Elizabeth K.] Univ Washington, Seattle, WA 98195 USA. [Sudore, Rebecca L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Sudore, Rebecca L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Berg, Karina M.] Yale Univ, Sch Med, New Haven, CT USA. [Fromme, Erik K.] Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97201 USA. [Arnold, Robert M.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Sect Palliat Care & Med Eth,Ctr Bioeth & Hlth Law, Pittsburgh, PA USA. RP Vig, EK (reprint author), 1660 Columbian Way,S 182 Eth, Seattle, WA 98108 USA. EM vigster@u.washington.edu FU Pfizer Fellowship in Clear Communication FX Dr. Sudore is supported in part by a Pfizer Fellowship in Clear Communication. The other authors have no sponsorship related to this manuscript. The authors have no financial conflicts of interest to disclose. NR 22 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD NOV PY 2011 VL 42 IS 5 BP 777 EP 782 DI 10.1016/j.jpainsymman.2011.08.003 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 847YL UT WOS:000297011800017 PM 22045374 ER PT J AU Pierre, JF Heneghan, AF Tsao, FHC Sano, Y Jonker, MA Omata, J Lan, JG Kudsk, KA AF Pierre, Joseph F. Heneghan, Aaron F. Tsao, Francis H. C. Sano, Yoshifumi Jonker, Mark A. Omata, Jiro Lan, Jinggang Kudsk, Kenneth A. TI Route and Type of Nutrition and Surgical Stress Influence Secretory Phospholipase A2 Secretion of the Murine Small Intestine SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article; Proceedings Paper CT Meeting of the American-Society-for-Parenteral-and-Enteral-Nutrition/Clinical Nutrition Week CY FEB 07, 2010 CL Las Vegas, NV SP Amer Soc Parenteral & Enteral Nutr DE secretory phospholipase A2; parenteral nutrition; surgical stress; small intestine; defensins; enteral feeding; innate immunity ID TOTAL PARENTERAL-NUTRITION; BACTERICIDAL PROPERTIES; INFLAMMATORY MEDIATORS; STAPHYLOCOCCUS-AUREUS; ENTERAL NUTRITION; LYMPHOID-TISSUE; CELL-WALL; GROUP-II; A(2); EXPRESSION AB Background: The function of secretory phospholipase A2 (sPLA2) is site dependent. In tissue, sPLA2 regulates eicosanoid production; in circulation, sPLA2 primes neutrophils; and in the intestinal lumen, sPLA2 provides innate bactericidal immunity as a defensin-related protein. Since parenteral nutrition (PN) primes leukocytes while suppressing intraluminal mucosal immunity, the authors hypothesized that (1) PN would diminish luminal sPLA2 activity but increase activity in intestinal tissue and serum and (2) stress would accentuate these changes. Methods: Mice received chow, a complex enteral diet (CED), intragastric PN (IG-PN), or PN in experiment 1 and chow, chow+stress, PN, or PN+stress in experiment 2. Results: In experiment 1, luminal sPLA2 activity was greatest in chow and decreased in CED, IG-PN, and PN, with PN lower than CED and IG-PN. Compared to that after chow, serum sPLA2 activity dropped after CED, IG-PN, and PN. Serum sPLA2 was higher in portal than systemic serum. In experiment 2, PN lowered luminal sPLA2 activity vs chow. Stress lowered luminal sPLA2 activity in chow, without change in PN. Following stress, luminal immunoglobulin A increased in chow but not PN. Serum sPLA2 activity increased in PN. Conclusions: PN attenuates sPLA2 activity in intestinal fluid, consistent with suppressed innate mucosal defense. Stress suppresses luminal fluid sPLA2 activity in chow but not the immunoglobulin A response; PN impairs both. Stress significantly elevates serum sPLA2 in PN-fed mice, consistent with known increased neutrophil priming with PN. PN reduces innate bactericidal immunity of the gut but upregulates serum proinflammatory products poststress. (JPEN J Parenter Enteral Nutr. 2011;35:748-756) C1 [Pierre, Joseph F.; Heneghan, Aaron F.; Sano, Yoshifumi; Jonker, Mark A.; Omata, Jiro; Lan, Jinggang; Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. [Pierre, Joseph F.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. [Heneghan, Aaron F.; Lan, Jinggang; Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. [Tsao, Francis H. C.] Univ Wisconsin, Dept Med, Div Allergy Pulm & Crit Care Med, Sch Med & Publ Hlth, Madison, WI USA. RP Kudsk, KA (reprint author), 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM kudsk@sur-gery.wisc.edu FU NIGMS NIH HHS [R01 GM53439, R01 GM053439] NR 32 TC 13 Z9 13 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD NOV PY 2011 VL 35 IS 6 BP 748 EP 756 DI 10.1177/0148607111414025 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 839UL UT WOS:000296394800011 PM 22042050 ER PT J AU Atesok, KI Alman, BA Schemitsch, EH Peyser, A Mankin, H AF Atesok, Kivanc I. Alman, Benjamin A. Schemitsch, Emil H. Peyser, Amos Mankin, Henry TI Osteoid Osteoma and Osteoblastoma SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Review ID PERCUTANEOUS RADIOFREQUENCY ABLATION; BONE-FORMING LESIONS; DIAGNOSTIC-ACCURACY; OPERATIVE TREATMENT; IMAGING FEATURES; CHILDREN; MANAGEMENT; RESECTION; SPINE; TUMOR AB Osteoid osteoma and osteoblastoma are commonly seen benign osteogenic bone neoplasms. Both tumors are typically seen in the second decade of life, with a notable predilection in males. Histologically, these tumors resemble each other, with characteristically increased osteoid tissue formation surrounded by vascular fibrous stroma and perilesional sclerosis. However, osteoblastomas are larger than osteoid osteomas, and they exhibit greater osteoid production and vascularity. Clinically, osteoid osteoma most commonly occurs in the long bones (eg, femur, tibia). The lesions cause night pain that is relieved with nonsteroidal anti-inflammatory drugs (NSAIDs). Osteoblastoma is most frequently located in the axial skeleton, and the pain is usually not worse at night and is less likely to be relieved with NSAIDs. Osteoblastoma can be locally aggressive; osteoid osteoma lacks growth potential. Osteoid osteoma may be managed nonsurgically with NSAIDs. When surgery is required, minimally invasive methods (eg, CT-guided excision, radiofrequency ablation) are preferred. Osteoblastoma has a higher rate of recurrence than does osteoid osteoma, and patients must be treated surgically with intralesional curettage or en bloc resection. C1 [Atesok, Kivanc I.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. [Alman, Benjamin A.] Hosp Sick Children, Div Orthopaed Surg, Toronto, ON M5G 1X8, Canada. [Schemitsch, Emil H.] Univ Toronto, St Michaels Hosp, Div Orthopaed, Dept Surg, Toronto, ON M5S 1A1, Canada. [Peyser, Amos] Shaare Zedek Med Ctr, Dept Orthoped, Jerusalem, Israel. [Mankin, Henry] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Atesok, KI (reprint author), Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. NR 45 TC 31 Z9 37 U1 1 U2 10 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD NOV PY 2011 VL 19 IS 11 BP 678 EP 689 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 839WI UT WOS:000296399800004 PM 22052644 ER PT J AU Dowsett, M Nielsen, TO A'Hern, R Bartlett, J Coombes, RC Cuzick, J Ellis, M Henry, NL Hugh, JC Lively, T McShane, L Paik, S Penault-Llorca, F Prudkin, L Regan, M Salter, J Sotiriou, C Smith, IE Viale, G Zujewski, JA Hayes, DF AF Dowsett, Mitch Nielsen, Torsten O. A'Hern, Roger Bartlett, John Coombes, R. Charles Cuzick, Jack Ellis, Matthew Henry, N. Lynn Hugh, Judith C. Lively, Tracy McShane, Lisa Paik, Soon Penault-Llorca, Frederique Prudkin, Ljudmila Regan, Meredith Salter, Janine Sotiriou, Christos Smith, Ian E. Viale, Giuseppe Zujewski, Jo Anne Hayes, Daniel F. TI Assessment of Ki67 in Breast Cancer: Recommendations from the International Ki67 in Breast Cancer Working Group SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID PATHOLOGISTS GUIDELINE RECOMMENDATIONS; IMPROVED SURGICAL OUTCOMES; PHASE-II TRIAL; POSTMENOPAUSAL WOMEN; CELL PROLIFERATION; AMERICAN SOCIETY; PROGNOSTIC VALUE; CLINICAL ONCOLOGY/COLLEGE; NEOADJUVANT CHEMOTHERAPY; PROGESTERONE-RECEPTORS AB Uncontrolled proliferation is a hallmark of cancer. In breast cancer, immunohistochemical assessment of the proportion of cells staining for the nuclear antigen Ki67 has become the most widely used method for comparing proliferation between tumor samples. Potential uses include prognosis, prediction of relative responsiveness or resistance to chemotherapy or endocrine therapy, estimation of residual risk in patients on standard therapy and as a dynamic biomarker of treatment efficacy in samples taken before, during, and after neoadjuvant therapy, particularly neoadjuvant endocrine therapy. Increasingly, Ki67 is measured in these scenarios for clinical research, including as a primary efficacy endpoint for clinical trials, and sometimes for clinical management. At present, the enormous variation in analytical practice markedly limits the value of Ki67 in each of these contexts. On March 12, 2010, an international panel of investigators with substantial expertise in the assessment of Ki67 and in the development of biomarker guidelines was convened in London by the cochairs of the Breast International Group and North American Breast Cancer Group Biomarker Working Party to consider evidence for potential applications. Comprehensive recommendations on preanalytical and analytical assessment, and interpretation and scoring of Ki67 were formulated based on current evidence. These recommendations are geared toward achieving a harmonized methodology, create greater between-laboratory and between-study comparability, and allow earlier valid applications of this marker in clinical practice. C1 [Dowsett, Mitch; Salter, Janine] Royal Marsden Hosp, Acad Dept Biochem, London SW3 6JJ, England. [Dowsett, Mitch; Salter, Janine] Breakthrough Breast Canc Ctr, London, England. [Nielsen, Torsten O.] Univ British Columbia, Vancouver Hosp, Vancouver, BC V5Z 1M9, Canada. [A'Hern, Roger] Inst Canc Res, Canc Res UK Clin Trials & Stat Unit, Surrey, England. [Bartlett, John] Univ Edinburgh, Western Gen Hosp, Edinburgh Canc Res Ctr, Edinburgh, Midlothian, Scotland. [Coombes, R. Charles] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Div Canc, London, England. [Cuzick, Jack] Univ London, Barts & London Sch Med & Dent, Wolfson Inst Prevent Med, London, England. [Ellis, Matthew] Washington Univ, Sch Med, Siteman Canc Ctr, Breast Canc Program, St Louis, MO USA. [Henry, N. Lynn; Hayes, Daniel F.] Univ Michigan, Ctr Comprehens Canc, Breast Oncol Program, Ann Arbor, MI 48109 USA. [Hugh, Judith C.] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. [Lively, Tracy] NCI, Diagnost Evaluat Branch, Canc Diag Program, Rockville, MD USA. [McShane, Lisa] NCI, Biometr Res Branch, DCTD, Bethesda, MD 20892 USA. [Paik, Soon] NSABP Fdn, Div Pathol, Pittsburgh, PA USA. [Penault-Llorca, Frederique] Univ Auvergne, Dept Biopathol, Clermont Ferrand, France. [Prudkin, Ljudmila] Hosp Univ Vall Hebron, Lab Patol Mol, Barcelona, Spain. [Regan, Meredith] Dana Farber Canc Inst, IBCSG Stat Ctr, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Regan, Meredith] Harvard Univ, Sch Med, Boston, MA USA. [Sotiriou, Christos] Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium. [Sotiriou, Christos] Breast Canc Translat Res Lab BCTL, Brussels, Belgium. [Smith, Ian E.] Royal Marsden Hosp, Breast Unit, London SW3 6JJ, England. [Viale, Giuseppe] Univ Milan, European Inst Oncol, Dept Pathol, Milan, Italy. [Zujewski, Jo Anne] NCI, Canc Therapy Evaluat Program, Rockville, MD USA. RP Dowsett, M (reprint author), Royal Marsden Hosp, Dept Biochem, Fulham Rd, London SW3 6JJ, England. EM mitch.dowsett@icr.ac.uk FU Cancer Research UK NR 55 TC 500 Z9 525 U1 3 U2 36 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 NOV PY 2011 VL 103 IS 22 BP 1656 EP 1664 DI 10.1093/jnci/djr393 PG 9 WC Oncology SC Oncology GA 850PV UT WOS:000297209000007 PM 21960707 ER PT J AU Zafar, SN Millham, FH Chang, YC Fikry, K Alam, HB King, DR Velmahos, GC de Moya, MA AF Zafar, Syed Nabeel Millham, Frederick H. Chang, Yuchiao Fikry, Karim Alam, Hasan B. King, David R. Velmahos, George C. de Moya, Marc A. TI Presenting Blood Pressure in Traumatic Brain Injury: A Bimodal Distribution of Death SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE Traumatic brain injury; Mortality; Blood pressure ID SEVERE HEAD-INJURY; 110 MM HG; PREHOSPITAL HYPOTENSION; TEAM ACTIVATION; BLUNT TRAUMA; REDEFINING HYPOTENSION; PROGNOSTIC VALUE; VALID INDICATOR; MORTALITY; IMPACT AB Background: Recent research explores the relationship between vital signs on arrival to the emergency department and early outcomes. This work has not included traumatic brain injury (TBI). We aimed to evaluate the relationship of the initial emergency department systolic blood pressure (EDSBP) with outcome. Methods: By using the National Trauma Data Bank (v7), we analyzed patients older than 16 years with isolated moderate to severe blunt TBI. TBI was defined by International Classification of Diseases-9th Rev diagnosis codes and Abbreviated Injury Scale scores. We determined mortality rates while controlling for age, gender, race, payment type, and injury severity using logistic regression. Survival analysis was performed to determine 3-day survival rates. Scores and rates were plotted against EDSBP. Results: A total of 7,238 patients were included in the analysis. Plots of adverse outcomes versus EDSBP demonstrated bimodal distributions. The mortality curve had one inflection point at EDSBP 120 mm Hg, indicating higher mortality when blood pressures were lower than this threshold. Another inflection began at EDSBP 140 mm Hg. The mortality rate was 21% when EDSBP was <120 mm Hg, 9% when it was between 120 mm Hg and 140 mm Hg, and 19% when EDSBP was >= 140 mm Hg. Multivariate analysis demonstrated that patients presenting with an EDSBP of <120 mm Hg and >= 140 mm Hg were 2.7 (95% confidence interval = 2.13,3.48) and 1.6 (95% confidence interval = 1.32,1.96) times more likely to die, respectively, than those who presented with a EDSBP of 120 mm Hg to 140 mm Hg. Conclusions: Mortality in moderate to severe TBI has a bimodal distribution. Like hypotension, hypertension at hospital admission seems to be associated with increased mortality in TBI, even after controlling for other factors. C1 [Fikry, Karim; Alam, Hasan B.; King, David R.; Velmahos, George C.; de Moya, Marc A.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Zafar, Syed Nabeel] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Millham, Frederick H.] Newton Wellesley Hosp, Dept Surg, Newton, MA USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP de Moya, MA (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM mdemoya@partners.org OI King, David/0000-0003-1028-1478; Zafar, Syed Nabeel/0000-0003-3843-9687 NR 31 TC 13 Z9 13 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 NOV PY 2011 VL 71 IS 5 BP 1179 EP 1184 DI 10.1097/TA.0b013e3182140d38 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 849IG UT WOS:000297118600021 PM 21502878 ER PT J AU Fang, Y Xu, P Gu, C Wang, Y Fu, XJ Yu, WR Yao, M AF Fang, Yong Xu, Peng Gu, Chuan Wang, Ying Fu, Xiu-Jun Yu, Wei-Rong Yao, Min TI Ulinastatin Improves Pulmonary Function in Severe Burn-Induced Acute Lung Injury by Attenuating Inflammatory Response SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE Ulinastatin; Thermal injury; Acute lung injury; Inflammatory response; Permeability ID URINARY TRYPSIN-INHIBITOR; RESPIRATORY-DISTRESS-SYNDROME; NEUTROPHIL CHEMOTACTIC FACTOR; ENDOTHELIAL-CELLS; SYSTEMIC INFLAMMATION; INHALATION INJURY; HEMORRHAGIC-SHOCK; GENE-EXPRESSION; TNF-ALPHA; ACTIVATION AB Background: Acute systemic inflammatory response to severe skin burn injury mediates burn-induced acute lung injury. Ulinastatin is potentially an effective intervention, because it attenuates the systemic inflammatory response induced by endotoxin and improves myocardial function during ischemic shock and reperfusion. Methods: Rats received full-thickness burn wounds to 30% total body surface area followed by delayed resuscitation. The treatment group received 50,000 U/kg of ulinastatin and the burn group was given vehicle only. A sham group was not burned but otherwise was treated identically. After killing, blood and lung samples were harvested for histology and measurement of inflammatory mediators. Results: Administration of ulinastatin significantly decreased the mRNA and protein levels of tumor necrosis factor-alpha, interleukin-1 beta, -6, and -8 both locally and systemically in burn-injured rats. The secretion of neutrophil elastase and myeloperoxidase in the lung and the expression of intercellular adhesion molecule-1 on the surface of lung epithelium were inhibited by ulinastatin. Ulinastatin also reduced the increase in pulmonary microvascular permeability. Consistent with these findings, ulinastatin ameliorated the lung edema and pulmonary oxygenation in burn-injured rats. Conclusions: These results indicate that the inhibitory effects of ulinastatin on inflammatory mediator production, neutrophil activation, and microvascular permeability are associated with the recovery of pulmonary functions in severe burn-induced acute lung injury and suggest that ulinastatin may serve as a potential therapeutic administration in critical burn care. C1 [Fang, Yong; Xu, Peng; Gu, Chuan; Wang, Ying; Fu, Xiu-Jun; Yu, Wei-Rong; Yao, Min] Shanghai Jiao Tong Univ, Peoples Hosp 3, Dept Burns & Plast Surg, Shanghai 201900, Peoples R China. Shanghai Jiao Tong Univ, Sch Med, Inst Traumat Med, Shanghai 201900, 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, Peoples Hosp 3, Dept Burns & Plast Surg, 280 Mohe Rd, Shanghai 201900, Peoples R China. EM myao2@partners.org FU Foundation of Nature and Science at the School of Medicine, Shanghai Jiao Tong University [09XJ21073] FX Supported by a grant from the Foundation of Nature and Science at the School of Medicine, Shanghai Jiao Tong University (09XJ21073). NR 25 TC 27 Z9 37 U1 1 U2 9 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 NOV PY 2011 VL 71 IS 5 BP 1297 EP 1304 DI 10.1097/TA.0b013e3182127d48 PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 849IG UT WOS:000297118600040 PM 21926648 ER PT J AU Liteplo, AS Noble, VE Attwood, BHC AF Liteplo, Andrew S. Noble, Vicki E. Attwood, Ben H. C. TI Real-time Video Streaming of Sonographic Clips Using Domestic Internet Networks and Free Videoconferencing Software SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE image quality; sonography; telesonography; videoconferencing; wireless ID PREHOSPITAL ULTRASOUND; TRAUMA AB Objectives-As the use of point-of-care sonography spreads, so too does the need for remote expert over-reading via telesonogrpahy. We sought to assess the feasibility of using familiar, widespread, and cost-effective existent technology to allow remote over-reading of sonograms in real time and to compare 4 different methods of transmission and communication for both the feasibility of transmission and image quality. Methods-Sonographic video clips were transmitted using 2 different connections (WiFi and 3G) and via 2 different videoconferencing modalities (iChat [Apple Inc, Cupertino, CA] and Skype [Skype Software Sarl, Luxembourg]), for a total of 4 different permutations. The clips were received at a remote location and recorded and then scored by expert reviewers for image quality, resolution, and detail. Results-Wireless transmission of sonographic clips was feasible in all cases when WiFi was used and when Skype was used over a 3G connection. Images transmitted via a WiFi connection were statistically superior to those transmitted via 3G in all parameters of quality (average P = .031), and those sent by iChat were superior to those sent by Skype but not statistically so (average P = .057). Conclusions-Wireless transmission of sonographic video clips using inexpensive hardware, free videoconferencing software, and domestic Internet networks is feasible with retention of image quality sufficient for interpretation. WiFi transmission results in greater image quality than transmission by a 3G network. C1 [Liteplo, Andrew S.; Noble, Vicki E.] Massachusetts Gen Hosp, Div Emergency Ultrasound, Dept Emergency Med, Boston, MA 02114 USA. [Attwood, Ben H. C.] Stoke Mandeville Hosp, Dept Anesthet & Intens Care, Aylesbury HP21 8AL, Bucks, England. RP Liteplo, AS (reprint author), Massachusetts Gen Hosp, Div Emergency Ultrasound, Dept Emergency Med, 0 Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM aliteplo@partners.org NR 16 TC 5 Z9 5 U1 0 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD NOV PY 2011 VL 30 IS 11 BP 1459 EP 1466 PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 846XN UT WOS:000296936600002 PM 22039018 ER PT J AU Shipp, TD Nguyen, HT Bromley, B Lyons, JG Benacerraf, BR AF Shipp, Thomas D. Nguyen, Hiep T. Bromley, Bryann Lyons, Jennifer G. Benacerraf, Beryl R. TI Importance of Renal Abnormalities First Identified in the Third Trimester After Normal Findings on a Detailed Second-Trimester Structural Fetal Survey SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE Renal abnormalities; structural survey; third trimester ID DILATATION; PREDICTOR AB Objectives-The purpose of this study was to evaluate the importance of renal abnormalities first identified in the third trimester of pregnancy after normal findings on a detailed second-trimester structural fetal survey. Methods-Between March 1, 2007, and August 1, 2009, all patients having a sonographic examination in the third trimester who previously had normal findings on a second-trimester detailed structural fetal survey were retrospectively identified. Fetal renal abnormalities first detected in the third trimester and not seen during the second-trimester survey were tabulated. Neonatal follow-up was obtained for those with sonographic abnormalities. Results-Overall, 4170 patients had third-trimester scans after normal findings on a detailed second-trimester survey. A new renal abnormality was detected in 77 (1.8%) of these third-trimester scans. Detailed postnatal imaging follow-up was available in 49 of 77 (63.6%), of which 44 (89.8%) had prenatal hydronephosis. Of these, 9 of 44 (20.5%) had reflux; 14 of 44 (31.8%) had normal findings or had hydronephosis that resolved on follow-up sonography after birth; and the rest had hydronephosis (13 of 44 [29.5%]), ureterovesical junction obstruction (3 of 44 [6.8%]), or ureteropelvic junction obstruction (5 of 44 [11.4%]). The other 5 fetuses with nonhydronephrotic renal abnormalities had pelvic kidneys (3) and unilateral renal agenesis (2). Two of those with reflux (22.2%) required surgery, and 1 of those with ureterovesical junction obstruction (33.3%) required surgery. Conclusions-Most renal abnormalities first identified in the third trimester after normal findings on a detailed second-trimester structural fetal survey were hydronephrosis, of which approximately one-third resolved after birth. Among the remaining neonates with persistent hydronephrosis, almost one-third had reflux that was not detected on the second-trimester anatomy scan. C1 [Shipp, Thomas D.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02115 USA. [Shipp, Thomas D.; Bromley, Bryann; Benacerraf, Beryl R.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Shipp, Thomas D.; Bromley, Bryann; Benacerraf, Beryl R.] Diagnost Ultrasound Associates PC, Boston, MA USA. [Shipp, Thomas D.; Bromley, Bryann; Benacerraf, Beryl R.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Benacerraf, Beryl R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Nguyen, Hiep T.] Childrens Hosp, Dept Urol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Lyons, Jennifer G.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Shipp, TD (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, CWN 3,75 Francis St, Boston, MA 02115 USA. EM tshipp@partners.mg NR 9 TC 3 Z9 3 U1 0 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD NOV PY 2011 VL 30 IS 11 BP 1567 EP 1572 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 846XN UT WOS:000296936600014 PM 22039030 ER PT J AU Iezzoni, LI AF Iezzoni, Lisa I. TI Last Word: Barbara Starfield's Road Map SO MEDICAL CARE LA English DT Editorial Material ID CARE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Iezzoni, LI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, 50 Staniford St,Suite 901H, Boston, MA 02114 USA. EM liezzoni@partners.org 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 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2011 VL 49 IS 11 BP 976 EP 977 DI 10.1097/MLR.0b013e318233a906 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 841UO UT WOS:000296540400003 PM 22005604 ER PT J AU Edwardsen, EA Dichter, ME Walsh, P Cerulli, C AF Edwardsen, Elizabeth A. Dichter, Melissa E. Walsh, Patrick Cerulli, Catherine TI Instructional Curriculum Improves Medical Staff Knowledge and Efficacy for Patients Experiencing Intimate Partner Violence SO MILITARY MEDICINE LA English DT Article ID DOMESTIC VIOLENCE; MENTAL-HEALTH; PRIMARY-CARE; WOMEN; PHYSICIANS; VICTIMS AB Objectives: This study assesses Veterans Affairs mental health providers' understanding of intimate partner violence (IPV) and the perception of patient benefit of routine inquiry and service referral. The impact of an instructional curriculum was also examined following an interactive training. Methods: An evidence-based curriculum was offered to Veterans Affairs mental health providers. The curriculum utilized didactic methods, case scenarios, and resources regarding referrals and statutes regarding crimes related to violence and abuse. The participants completed pre- and post-training surveys to assess their perceptions about IPV and to evaluate the training. Results: Seventy-three individuals completed the training. Fifty-four of the participants were female, and thirty-three were over the age of 45 years. Fifty-one individuals completed both surveys. There were no differences between participants' views of the seriousness of IPV in the community or their practices before or after the training. However, participants scored significantly higher on the knowledge and efficacy measures after the training (p < 0.001). Conclusion: Following an educational intervention, providers demonstrate more knowledge and efficacy regarding routine inquiry and referral for IPV. Barriers to universal implementation still warrant attention. C1 [Edwardsen, Elizabeth A.] Univ Rochester, Sch Med & Dent, Dept Emergency Med, Rochester, NY 14642 USA. [Dichter, Melissa E.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Walsh, Patrick] Univ Rochester, Sch Med & Dent, Ctr Excellence, Dept Psychiat, Rochester, NY 14642 USA. [Cerulli, Catherine] Univ Rochester, Sch Med & Dent, Dept Psychiat, Lab Interpersonal Violence & Victimizat, Rochester, NY 14642 USA. RP Edwardsen, EA (reprint author), Univ Rochester, Sch Med & Dent, Dept Emergency Med, 601 Elmwood Ave, Rochester, NY 14642 USA. FU NIMH [K01MH75965-01]; Center of Excellence for Suicide Prevention, Department of VA FX Funding for this work is provided by NIMH K01MH75965-01 (C. Cerulli). Additional funding is provided by the Center of Excellence for Suicide Prevention, Department of VA. NR 25 TC 3 Z9 4 U1 0 U2 5 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD NOV PY 2011 VL 176 IS 11 BP 1260 EP 1264 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 845NR UT WOS:000296830300009 PM 22165653 ER PT J AU Qin, Y Ekmekcioglu, S Liu, P Duncan, LM Lizee, G Poindexter, N Grimm, EA AF Qin, Yong Ekmekcioglu, Suhendan Liu, Ping Duncan, Lyn M. Lizee, Gregory Poindexter, Nancy Grimm, Elizabeth A. TI Constitutive Aberrant Endogenous Interleukin-1 Facilitates Inflammation and Growth in Human Melanoma SO MOLECULAR CANCER RESEARCH LA English DT Article ID FACTOR-KAPPA-B; SUPPRESSOR-CELLS; CANCER; EXPRESSION; REGULATORS; APOPTOSIS; AUTOPHAGY; PATHWAY; METASTASIS; ACTIVATION AB Interleukin (IL)-1-mediated inflammation is proposed to contribute to the development and progression of some cancers. IL-1 family member proteins are known to be expressed constitutively in many melanoma tumor cells, and we hypothesize that these support molecular pathways of inflammation and facilitate tumor growth. To investigate the expression of IL-1 alpha and IL-1 beta in melanoma patients, and their association with disease progression, immunohistochemical staining was carried out on tissues from 170 patients including benign nevi, primary melanomas, and metastatic melanomas. IL-1 beta levels were low (or zero) in benign nevi and higher in primary and metastatic melanomas (P < 0.0001). IL-1 alpha was expressed in about 73% of nevi and 55% of metastatic melanomas, with levels significantly higher in primary tumors (P < 0.0001); most (98%) primary melanoma samples were positive for IL-1 alpha. In vitro studies with seven human melanoma cell lines showed that five cell lines expressed IL-1 alpha and IL-1 beta proteins and mRNA. We identified for the first time several important downstream signaling pathways affected by endogenous IL-1, including reactive oxygen and nitrogen species, COX-2, and phosphorylated NF-kappa B inhibitor (I kappa B) and stress-activated protein kinase/c-jun-NH2-kinase; all of which were decreased by siRNA to IL-1s. Downregulation of IL-1 alpha, IL-1 beta, or MyD88 substantially increased p21 and p53 levels. Treatment with IL-1 receptor type I neutralizing antibody or IL-1 pathway-specific siRNAs led to growth arrest in IL-1-positive melanoma cells. Furthermore, blocking the IL-1 pathway increased autophagy in IL-1-positive melanoma cells. These results indicate that the endogenous IL-1 system is functional in most human melanoma and interrupting its signaling inhibits the growth of IL-1-positive melanoma cells. Mol Cancer Res; 9(11); 1537-50. (C) 2011 AACR. C1 [Qin, Yong; Ekmekcioglu, Suhendan; Lizee, Gregory; Poindexter, Nancy; Grimm, Elizabeth A.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [Liu, Ping] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Duncan, Lyn M.] Massachusetts Gen Hosp, Pathol Serv, Dept Dermatopathol Unit, Boston, MA 02114 USA. RP Grimm, EA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Box 362,1515 Holcombe Blvd, Houston, TX 77030 USA. EM egrimm@mdanderson.org FU National Cancer Institute [CA16672]; University of Texas, MD Anderson Cancer Center [P50 CA093459]; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation FX The authors thank Sandra Kinney (MD Anderson) for assistance in the IHC studies and Wendy Schawa (MD Anderson) for assistance in flow cytometric studies. The authors are grateful to Karen Muller for proofreading and editing the manuscript and figures and also thank MDACC Characterized Cell Line Core Facility for STR DNA fingerprinting of the melanoma cell lines, the Flow Cytometry, and Cellular Imagine Facility at MD Anderson (funded by National Cancer Institute CA16672) for AO staining analysis.; This research was supported by the University of Texas, MD Anderson Cancer Center SPORE in Melanoma (P50 CA093459) and Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. NR 38 TC 32 Z9 33 U1 0 U2 5 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 NOV PY 2011 VL 9 IS 11 BP 1537 EP 1550 DI 10.1158/1541-7786.MCR-11-0279 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 850QH UT WOS:000297211100011 PM 21954434 ER PT J AU Gerstner, E Jennings, D Chi, AS Plotkin, S Kwon, SJ Pinho, M Polaskova, P Batchelor, TT Sorensen, AG AF Gerstner, Elizabeth Jennings, Dominique Chi, Andrew S. Plotkin, Scott Kwon, Seon Joo Pinho, Marco Polaskova, Pavlina Batchelor, Tracy T. Sorensen, A. Gregory TI COMPARISON OF CHANGES IN MRI CONTRAST ENHANCEMENT AND FLAIR HYPERINTENSITY IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA DURING CHEMORADIATION WITH AND WITHOUT AN ANTI-VEGF AGENT SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Gerstner, Elizabeth; Chi, Andrew S.; Plotkin, Scott; Batchelor, Tracy T.; Sorensen, A. Gregory] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jennings, Dominique; Kwon, Seon Joo; Pinho, Marco; Polaskova, Pavlina] Martinos Ctr Biomed Imaging, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 7 EP 8 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600032 ER PT J AU Furnari, F Fenton, T Nathanson, D de Alberquerque, CP Kuga, D Wanami, A Dang, J Yang, HJ Tanaka, K Gao, L Oba-Shinjo, S Uno, M Inda, M Bachoo, R James, CD DePinho, R Vandenberg, S Zhou, HL Marie, S Mischel, P Cavenee, W AF Furnari, Frank Fenton, Timothy Nathanson, David de Alberquerque, Claudio Ponte Kuga, Daisuke Wanami, Akio Dang, Julie Yang, Huijun Tanaka, Kazuhiro Gao, Lu Oba-Shinjo, Sueli Uno, Miyuki Inda, Maria-del-Mar Bachoo, Robert James, C. David DePinho, Ronald Vandenberg, Scott Zhou, Huilin Marie, Suely Mischel, Paul Cavenee, Webster TI PTEN PHOSPHORYLATION BY FIBROBLAST GROWTH FACTOR RECEPTORS AND SRC MEDIATES RESISTANCE TO EPIDERMAL GROWTH FACTOR RECEPTOR INHIBITORS IN GLIOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Furnari, Frank; Fenton, Timothy; de Alberquerque, Claudio Ponte; Gao, Lu; Inda, Maria-del-Mar; Zhou, Huilin; Cavenee, Webster] Ludwig Inst UCSD, La Jolla, CA USA. [Nathanson, David; Kuga, Daisuke; Wanami, Akio; Dang, Julie; Yang, Huijun; Tanaka, Kazuhiro; Mischel, Paul] Univ Calif Los Angeles, Los Angeles, CA USA. [Oba-Shinjo, Sueli; Uno, Miyuki] Univ Sao Paulo, Sao Paulo, Brazil. [Bachoo, Robert] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [James, C. David] Univ Calif San Francisco, San Francisco, CA 94143 USA. [DePinho, Ronald] Dana Farber Canc Inst, Boston, MA USA. [Vandenberg, Scott] Univ Calif San Diego, La Jolla, CA 92093 USA. [Marie, Suely] Univ Sao Paulo, Sao Paulo, CA, Brazil. RI James, Charles/E-2721-2012; Marie, Suely/D-1870-2012; Oba-Shinjo, Sueli /C-4017-2012 OI James, Charles/0000-0002-1027-203X; NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2011 VL 13 SU 3 BP 10 EP 10 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600039 ER PT J AU Kouri, FM Chin, L Stegh, AH AF Kouri, Foteini M. Chin, Lynda Stegh, Alexander H. TI MICRORNA-182 ACTS AS A CHEMOSENSITIZER IN GBM BY REPRESSING BCL2L12 SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Kouri, Foteini M.; Stegh, Alexander H.] Northwestern Univ, Chicago, IL 60611 USA. [Chin, Lynda] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 24 EP 24 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600101 ER PT J AU Terry, AR Barker, FG Leffert, LR Bateman, B Souter, I Plotkin, SR AF Terry, Anna R. Barker, Fred G., II Leffert, Lisa R. Bateman, Brian Souter, Irene Plotkin, Scott R. TI OUTCOMES OF HOSPITALIZATION AMONG PREGNANT WOMEN WITH CNS NEOPLASMS: A POPULATION-BASED STUDY SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Terry, Anna R.; Barker, Fred G., II; Leffert, Lisa R.; Bateman, Brian; Souter, Irene; Plotkin, Scott R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 28 EP 28 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600119 ER PT J AU Kleijn, A Kloezeman, J Treffers-Westerlaken, E Fulci, G Leenstra, S Dirven, C Debets, R Lamfers, M AF Kleijn, Anne Kloezeman, Jenneke Treffers-Westerlaken, Elike Fulci, Giulia Leenstra, Sieger Dirven, Clemens Debets, Reno Lamfers, Martine TI CHARACTERIZATION OF THE IMMUNE RESPONSE TO ONCOLYTIC ADENOVIRUS THERAPY FOR MALIGNANT GLIOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Kleijn, Anne; Kloezeman, Jenneke; Treffers-Westerlaken, Elike; Leenstra, Sieger; Dirven, Clemens; Debets, Reno; Lamfers, Martine] Erasmus MC, Rotterdam, Netherlands. [Fulci, Giulia] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 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 NOV PY 2011 VL 13 SU 3 BP 32 EP 32 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600132 ER PT J AU Kong, S Tyler, B Zhou, JY Carter, BS Brem, H Junghans, RP Sampath, P AF Kong, Seogkyoung Tyler, Betty Zhou, Jinyuan Carter, Bob S. Brem, Henry Junghans, Richard P. Sampath, Prakash TI SUCCESSFUL SUPPRESSION OF A HUMAN GLIOMA XENOGRAFT USING IL13RA2-SPECIFIC MONOMERIC CHIMERIC ANTIGEN RECEPTOR SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Kong, Seogkyoung; Sampath, Prakash] Boston Univ, Sch Med, Roger Williams Med Ctr, Dept Neurosurg, Providence, RI USA. [Tyler, Betty; Brem, Henry] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Hunterian Neurosurg Res Lab, Baltimore, MD 21205 USA. [Zhou, Jinyuan] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Carter, Bob S.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Neurosurg Serv, Boston, MA 02115 USA. [Junghans, Richard P.] Boston Univ, Sch Med, Roger Williams Hosp, Dept Surg,Div Surg Res, Providence, RI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2011 VL 13 SU 3 BP 34 EP 34 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600138 ER PT J AU Cloughesy, T Raizer, J Drappatz, J Gerena-Lewis, M Rogerio, J Yacoub, S Desjardin, A AF Cloughesy, Timothy Raizer, J. Drappatz, J. Gerena-Lewis, M. Rogerio, J. Yacoub, S. Desjardin, A. TI A PHASE II TRIAL OF EVEROLIMUS IN PATIENTS WITH RECURRENT GLIOBLASTOMA MULTIFORME SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Cloughesy, Timothy] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Raizer, J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Drappatz, J.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Gerena-Lewis, M.] Summit Oncol Associates, Akron, OH USA. [Rogerio, J.; Yacoub, S.] Novartis Pharmaceut, Florham Pk, NJ USA. [Desjardin, A.] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 1 Z9 1 U1 1 U2 1 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 NOV PY 2011 VL 13 SU 3 BP 42 EP 43 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600172 ER PT J AU Reiner, AS Panageas, KS Iwamoto, FM Cloughesy, TF Aldape, KD Rivera, AL Eichler, AF Louis, DN Paleologos, NA Fisher, BJ Ashby, LS Cairncross, JG Roldan, GB Wen, PY Ligon, KL Shiff, D Robins, HI Rocque, BG Chamberlain, MC Mason, WP Weaver, SA Green, RM Kamar, FG Abrey, LE DeAngelis, LM Jhanwar, SC Rosenblum, MK Lassman, AB AF Reiner, Anne S. Panageas, Katherine S. Iwamoto, Fabio M. Cloughesy, Timothy F. Aldape, Kenneth D. Rivera, Andreana L. Eichler, April F. Louis, David N. Paleologos, Nina A. Fisher, Barbara J. Ashby, Lynn S. Cairncross, J. G. Roldan, Gloria B. Wen, Patrick Y. Ligon, Keith L. Shiff, David Robins, H. I. Rocque, Brandon G. Chamberlain, Marc C. Mason, Warren P. Weaver, Susan A. Green, Richard M. Kamar, Francois G. Abrey, Lauren E. DeAngelis, Lisa M. Jhanwar, Suresh C. Rosenblum, Marc K. Lassman, Andrew B. TI RECURSIVE PARTITIONING ANALYSIS OF PROGNOSTIC VARIABLES IN NEWLY DIAGNOSED ANAPLASTIC OLIGODENDROGLIAL TUMORS SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Reiner, Anne S.; Panageas, Katherine S.; Iwamoto, Fabio M.; Abrey, Lauren E.; DeAngelis, Lisa M.; Jhanwar, Suresh C.; Rosenblum, Marc K.; Lassman, Andrew B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Aldape, Kenneth D.; Rivera, Andreana L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Eichler, April F.; Louis, David N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Paleologos, Nina A.] NorthShore Univ Hlth Syst, Evanston Hosp Kellogg Canc, Pritzker Sch Med, Evanston, IL USA. [Fisher, Barbara J.] London Reg Canc Program, London, ON, Canada. [Ashby, Lynn S.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Cairncross, J. G.; Roldan, Gloria B.] Univ Calgary, Calgary, AB, Canada. [Wen, Patrick Y.; Ligon, Keith L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wen, Patrick Y.; Ligon, Keith L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shiff, David] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Robins, H. I.; Rocque, Brandon G.] Univ Wisconsin, Madison, WI USA. [Chamberlain, Marc C.] Univ Washington, Seattle, WA 98195 USA. [Chamberlain, Marc C.] Seattle Canc Care Alliance, Seattle, WA USA. [Mason, Warren P.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Green, Richard M.] Kaiser Permanente Angeles Med Ctr, Los Angeles, CA USA. [Weaver, Susan A.] Albany Med Ctr, Albany, NY USA. [Kamar, Francois G.] Clemenceau Med Ctr, Beirut, Lebanon. NR 0 TC 2 Z9 2 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 43 EP 44 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600176 ER PT J AU Sparagana, S Belousova, E Jozwiak, S Korf, B Frost, M Kuperman, R Kohrman, M Witt, O Wu, J Flamini, R Jansen, A Curtalolo, P Thiele, E Whittemore, V De Vries, P Ford, J Shah, G Cauwel, H Edrich, P Sahmoud, T Franz, D AF Sparagana, Steven Belousova, E. Jozwiak, Sergiusz Korf, Bruce Frost, Michael Kuperman, Rachel Kohrman, Michael Witt, Olaf Wu, Joyce Flamini, Robert Jansen, Anna Curtalolo, P. Thiele, E. Whittemore, V. De Vries, Petrus Ford, James Shah, Gaurav Cauwel, H. Edrich, Pascal Sahmoud, Tarek Franz, David TI EVEROLIMUS TREATMENT OF SUBEPENDYMAL GIANT CELL ASTROCYTOMAS (SEGAs) ASSOCIATED WITH TUBEROUS SCLEROSIS COMPLEX (TSC): THE EXIST-1 TRIAL SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Sparagana, Steven] Texas Scottish Rite Hosp Children, Dallas, TX 75219 USA. [Belousova, E.] Moscow Res Inst Pediat Pediat Surg, Moscow, Russia. [Jozwiak, Sergiusz] Childrens Mem Hlth Inst Warsaw, Warsaw, Poland. [Korf, Bruce] Univ Alabama, Birmingham, AL USA. [Frost, Michael] Minnesota Epilepsy Grp, St Paul, MN USA. [Kuperman, Rachel] Childrens Hosp & Res Ctr Oakland, Oakland, CA USA. [Kohrman, Michael] Univ Chicago, Chicago, IL 60637 USA. [Kohrman, Michael] Comer Childrens Hosp, Chicago, IL USA. [Witt, Olaf] Univ Heidelberg, Med Ctr, Heidelberg, Germany. [Witt, Olaf] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Wu, Joyce] Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA USA. [Flamini, Robert] Childrens Healthcare Atlanta, Atlanta, GA USA. [Jansen, Anna] UZ Brussel, Brussels, Belgium. [Curtalolo, P.] Univ Rome Tor Vega, Rome, Italy. [Thiele, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Whittemore, V.] Tuberous Sclerosis Alliance, Silver Spring, MD USA. [De Vries, Petrus] Univ Cambridge, Neurodev Serv, Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England. [De Vries, Petrus] Univ Cambridge, Dev Psychiat Sect, Cambridge, England. [Ford, James; Shah, Gaurav; Cauwel, H.; Edrich, Pascal; Sahmoud, Tarek] Novartis Pharmaceut, Florham Pk, NJ USA. [Franz, David] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. RI Jansen, Anna/P-3121-2014 OI Jansen, Anna/0000-0002-3835-2824 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2011 VL 13 SU 3 BP 50 EP 50 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600202 ER PT J AU Ram, Z Wong, ET Gutin, PH AF Ram, Zvi Wong, Eric T. Gutin, Philip H. TI COMPARING THE EFFECT OF NOVOTTF TO BEVACIZUMAB IN RECURRENT GBM: A POST-HOC SUB-ANALYSIS OF THE PHASE III TRIAL DATA SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Ram, Zvi] Tel Aviv Med Ctr & Sch Med, Dana Childrens Hosp, IL-64239 Tel Aviv, Israel. [Wong, Eric T.] BIDMC, Boston, MA USA. [Gutin, Philip H.] NYC, MSKCC, New York, NY USA. NR 0 TC 1 Z9 1 U1 1 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 NOV PY 2011 VL 13 SU 3 BP 52 EP 52 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600211 ER PT J AU Nunes, FP Merker, V Jennings, D Caruso, P Muzikansky, A Stemmer-Rachamimov, A Plotkin, S AF Nunes, Fabio P. Merker, Vanessa Jennings, Dominique Caruso, Paul Muzikansky, Alona Stemmer-Rachamimov, Anat Plotkin, Scott TI MENINGIOMA RESPONSE TO BEVACIZUMAB: A RETROSPECTIVE ANALYSIS OF TREATMENT RESULTS IN 14 NF2 PATIENTS SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Nunes, Fabio P.; Merker, Vanessa; Jennings, Dominique; Caruso, Paul; Muzikansky, Alona; Stemmer-Rachamimov, Anat; Plotkin, Scott] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 59 EP 59 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600240 ER PT J AU Nayak, L Iwamoto, FM Rudnick, JD Norden, AD Omuro, A Kaley, TJ AF Nayak, Lakshmi Iwamoto, Fabio M. Rudnick, Jeremy D. Norden, Andrew D. Omuro, Antonio Kaley, Thomas J. TI BEVACIZUMAB IN MULTIPLY RECURRENT AGGRESSIVE MENINGIOMAS SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Nayak, Lakshmi; Omuro, Antonio; Kaley, Thomas J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Iwamoto, Fabio M.] NCI, NIH, Bethesda, MD 20892 USA. [Rudnick, Jeremy D.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Norden, Andrew D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 61 EP 61 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600248 ER PT J AU Panageas, KS Iwamoto, FM Cloughesy, TF Aldape, KD Rivera, AL Eichler, AF Louis, DN Paleologos, NA Fisher, BJ Ashby, LS Cairncross, JG Roldan, GB Wen, PY Ligon, KL Schiff, D Robins, HI Rocque, BG Chamberlain, MC Mason, WP Weaver, SA Green, RM Kamar, FG Abrey, LE DeAngelis, LM Jhanwar, SC Rosenblum, MK Lassman, AB AF Panageas, Katherine S. Iwamoto, Fabio M. Cloughesy, Timothy F. Aldape, Kenneth D. Rivera, Andreana L. Eichler, April F. Louis, David N. Paleologos, Nina A. Fisher, Barbara J. Ashby, Lynn S. Cairncross, J. G. Roldan, Gloria B. Wen, Patrick Y. Ligon, Keith L. Schiff, David Robins, H. I. Rocque, Brandon G. Chamberlain, Marc C. Mason, Warren P. Weaver, Susan A. Green, Richard M. Kamar, Francois G. Abrey, Lauren E. DeAngelis, Lisa M. Jhanwar, Suresh C. Rosenblum, Marc K. Lassman, Andrew B. TI TIME TRENDS IN TREATMENT OF ANAPLASTIC OLIGODENDROGLIAL TUMORS SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Panageas, Katherine S.; Iwamoto, Fabio M.; Abrey, Lauren E.; DeAngelis, Lisa M.; Jhanwar, Suresh C.; Rosenblum, Marc K.; Lassman, Andrew B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Aldape, Kenneth D.; Rivera, Andreana L.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Eichler, April F.; Louis, David N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Paleologos, Nina A.] NorthShore Univ HealthSyst, Evanston Hosp, Kellogg Canc Ctr, Evanston, IL USA. [Fisher, Barbara J.] London Reg Canc Program, London, ON, Canada. [Ashby, Lynn S.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Cairncross, J. G.; Roldan, Gloria B.] Univ Calgary, Calgary, AB, Canada. [Wen, Patrick Y.; Ligon, Keith L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wen, Patrick Y.; Ligon, Keith L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schiff, David] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Robins, H. I.; Rocque, Brandon G.] Univ Wisconsin, Madison, WI USA. [Chamberlain, Marc C.] Univ Washington, Seattle, WA 98195 USA. [Chamberlain, Marc C.] Seattle Canc Care Alliance, Seattle, WA USA. [Mason, Warren P.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Weaver, Susan A.] Albany Med Ctr, Albany, NY USA. [Green, Richard M.] Kaiser Permanente, Los Angeles Med Ctr, Los Angeles, CA USA. [Kamar, Francois G.] Clemenceau Med Ctr, Beirut, Lebanon. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 62 EP 63 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600256 ER PT J AU Rangarajan, HG Kieran, MW Scott, RM Lew, SM Firat, SY Segura, AD Jogal, SA AF Rangarajan, Hemalatha G. Kieran, Mark W. Scott, Robert M. Lew, Sean M. Firat, Selim Y. Segura, Annette D. Jogal, Sachin A. TI RECURRENT PAPILLARY TUMOR OF THE PINEAL REGION (PTPR) IN A PEDIATRIC PATIENT: A BRIEF REPORT SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Rangarajan, Hemalatha G.; Lew, Sean M.; Firat, Selim Y.; Segura, Annette D.; Jogal, Sachin A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Kieran, Mark W.; Scott, Robert M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI champier, jacques/B-4160-2012; Rangarajan, Hemalatha/E-2011-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 62 EP 62 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600252 ER PT J AU Plotkin, SR Supko, JG Curry, WT Chi, AS Gerstner, ER Stemmer-Rachamimov, A Batchelor, TT AF Plotkin, Scott R. Supko, Jeffrey G. Curry, William T. Chi, Andrew S. Gerstner, Elizabeth R. Stemmer-Rachamimov, Anat Batchelor, Tracy T. TI INTRATUMORAL CONCENTRATIONS OF SUNITINIB AFTER ORAL ADMINISTRATION IN PATIENTS WITH HIGH GRADE GLIOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Plotkin, Scott R.; Supko, Jeffrey G.; Curry, William T.; Chi, Andrew S.; Gerstner, Elizabeth R.; Stemmer-Rachamimov, Anat; Batchelor, Tracy T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 66 EP 66 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600271 ER PT J AU Plotkin, SR Halpin, C Merker, V Barker, FG AF Plotkin, Scott R. Halpin, Chris Merker, Vanessa Barker, Fred G., II TI HEARING AND RADIOGRAPHIC RESPONSE OF NEUROFIBROMATOSIS 2-RELATED VESTIBULAR SCHWANNOMA TO BEVACIZUMAB: A RETROSPECTIVE REVIEW OF 31 PATIENTS SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Plotkin, Scott R.; Merker, Vanessa; Barker, Fred G., II] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Halpin, Chris] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 67 EP 67 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600277 ER PT J AU Guo, DL Reinitz, F Youssef, M Hong, C Nathanson, D Akhavan, D Kuga, D Amzajerdi, AN Soto, H Zhu, SJ Babic, I Iwanami, A Tanaka, K Gini, B DeJesus, J Lisiero, DD Huang, T Prins, R Wen, P Robbins, HI Prados, M DeAngelis, L Mellinghoff, I Mehta, M James, CD Chakravarti, A Cloughesy, T Tontonoz, P Mischel, P AF Guo, Deliang Reinitz, Felicia Youssef, Mary Hong, Cynthia Nathanson, David Akhavan, David Kuga, Daisuke Amzajerdi, Ali Nael Soto, Horacio Zhu, Shaojun Babic, Ivan Iwanami, Akio Tanaka, Kazuhiro Gini, Beatrice DeJesus, Jason Lisiero, Dominique D. Huang, Tiffany Prins, Robert Wen, Patrick Robbins, H. Ian Prados, Michael DeAngelis, Lisa Mellinghoff, Ingo Mehta, Minesh James, C. David Chakravarti, Arnab Cloughesy, Timothy Tontonoz, Peter Mischel, Paul TI TARGETING EGFR/PI3K/AKT REGULATED SREBP-1/LDLR MEDIATED CHOLESTEROL METABOLISM TO TREAT GLIOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Guo, Deliang; Chakravarti, Arnab] Ohio State Univ, James Comprehens Canc Ctr, Columbus, OH 43210 USA. [Reinitz, Felicia; Youssef, Mary; Hong, Cynthia; Nathanson, David; Akhavan, David; Kuga, Daisuke; Amzajerdi, Ali Nael; Soto, Horacio; Zhu, Shaojun; Babic, Ivan; Iwanami, Akio; Tanaka, Kazuhiro; Gini, Beatrice; DeJesus, Jason; Lisiero, Dominique D.; Huang, Tiffany; Prins, Robert; Cloughesy, Timothy; Tontonoz, Peter; Mischel, Paul] Univ Calif Los Angeles, Los Angeles, CA USA. [Wen, Patrick] Dana Farber Canc Inst, Boston, MA 02115 USA. [Robbins, H. Ian] Univ Wisconsin, Madison, WI USA. [Prados, Michael; James, C. David] UCSF, San Francisco, CA USA. [DeAngelis, Lisa; Mellinghoff, Ingo] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mehta, Minesh] Northwestern Univ, Chicago, IL 60611 USA. RI James, Charles/E-2721-2012; Guo, Deliang/I-3735-2014 OI James, Charles/0000-0002-1027-203X; Guo, Deliang/0000-0002-8359-390X NR 0 TC 0 Z9 0 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 NOV PY 2011 VL 13 SU 3 BP 70 EP 71 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600290 ER PT J AU Zhang, W Zhang, J Hoadley, K Carter, B Li, SW Kang, CS You, YP Jiang, CL Song, SY Jiang, T Chen, C AF Zhang, Wei Zhang, Jing Hoadley, Katherine Carter, Bob Li, Shouwei Kang, Chunsheng You, Yongping Jiang, Chuanlu Song, Sonya Jiang, Tao Chen, Clark TI MIR-181D: A PREDICTIVE GLIOBLASTOMA BIOMARKER THAT DOWNREGULATES MGMT EXPRESSION SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Zhang, Wei; Li, Shouwei; Jiang, Tao] Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China. [Zhang, Jing] Beijing Inst Genom, Beijing, Peoples R China. [Hoadley, Katherine] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Carter, Bob] Univ Calif San Diego, Div Neurosurg, San Diego, CA 92103 USA. [Kang, Chunsheng] Tianjin Hosp, Lab Neurooncol, Tianjin, Peoples R China. [You, Yongping] Jiangsu Prov Peoples Hosp, Dept Neurosurg, Nanjing, Peoples R China. [Jiang, Chuanlu] Harbin Med Coll, Dept Neurosurg, Harbin, Peoples R China. [Song, Sonya] Peking Univ, Sch Oncol, Beijing 100871, Peoples R China. [Chen, Clark] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Jiang, Tao/N-8142-2014; Zhang, Jing/F-4707-2015 OI Zhang, Jing/0000-0001-5903-6487 NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV PY 2011 VL 13 SU 3 BP 77 EP 77 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600312 ER PT J AU Sperduto, PW Kased, N Roberge, D Xu, ZY Shanley, R Luo, XH Sneed, PK Chao, ST Weil, RJ Suh, J Bhatt, A Jensen, AW Brown, PD Shih, HA Kirkpatrick, J Gaspar, LE Fiveash, JB Chiang, V Knisely, JP Sperduto, CM Lin, N Mehta, MP AF Sperduto, Paul W. Kased, Norbert Roberge, David Xu, Zhiyuan Shanley, Ryan Luo, Xianghua Sneed, Penny K. Chao, Samuel T. Weil, Robert J. Suh, John Bhatt, Amit Jensen, Ashley W. Brown, Paul D. Shih, Helen A. Kirkpatrick, John Gaspar, Laurie E. Fiveash, John B. Chiang, Veronica Knisely, Jonathan P. Sperduto, Christina M. Lin, Nancy Mehta, Minesh P. TI THE EFFECT OF TUMOR SUBTYPE ON SURVIVAL AND THE GRADED PROGNOSTIC ASSESSMENT (GPA) FOR PATIENTS WITH BREAST CANCER AND BRAIN METASTASES SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Shanley, Ryan] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Kased, Norbert; Sneed, Penny K.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA. [Roberge, David] McGill Univ, Dept Radiat Oncol, Ctr Hlth, Montreal, PQ H3A 2T5, Canada. [Xu, Zhiyuan; Weil, Robert J.] Cleveland Clin, Dept Neurosurg, Cleveland, OH 44106 USA. [Luo, Xianghua] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Bhatt, Amit] Univ Wisconsin, Dept Human Oncol, Madison, WI USA. [Shih, Helen A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Kirkpatrick, John] Duke Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Gaspar, Laurie E.] Univ Colorado, Sch Med, Dept Radiat Oncol, Aurora, CO USA. [Fiveash, John B.] Univ Alabama, Dept Radiat Oncol, Birmingham, AL USA. [Chiang, Veronica] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Knisely, Jonathan P.] Yale Univ, Sch Med, Dept Radiat Oncol, New Haven, CT USA. [Sperduto, Christina M.] Dartmouth Coll, Hanover, NH 03755 USA. [Lin, Nancy] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mehta, Minesh P.] Northwestern Univ, Dept Radiat Oncol, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 82 EP 82 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600333 ER PT J AU Lee, EQ Batchelor, TT Lassman, AB Schiff, DS Kaley, TJ Wong, ET Mikkelsen, T Purow, BW Drappatz, J Norden, AD Beroukhim, R Weiss, S Alexander, BM Sceppa, C Gerard, M Hallisey, SD Bochacki, CA Smith, KH Muzikansky, AM Wen, PY AF Lee, Eudocia Quant Batchelor, Tracy T. Lassman, Andrew B. Schiff, David S. Kaley, Thomas J. Wong, Eric T. Mikkelsen, Tom Purow, Benjamin W. Drappatz, Jan Norden, Andrew D. Beroukhim, Rameen Weiss, Stephanie Alexander, Brian M. Sceppa, Christine Gerard, Mary Hallisey, Stephen D. Bochacki, Caelainn A. Smith, Katrina H. Muzikansky, Alona M. Wen, Patrick Y. TI PRELIMINARY DATA FROM A MULTICENTER, PHASE II, RANDOMIZED, NONCOMPARATIVE CLINICAL TRIAL OF RADIATION THERAPY AND TEMOZOLOMIDE WITH OR WITHOUT VANDETANIB IN NEWLY-DIAGNOSED GLIOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Lee, Eudocia Quant; Drappatz, Jan; Norden, Andrew D.; Beroukhim, Rameen; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Batchelor, Tracy T.; Muzikansky, Alona M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lassman, Andrew B.; Kaley, Thomas J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Schiff, David S.; Purow, Benjamin W.] Univ Virginia, Charlottesville, VA USA. [Wong, Eric T.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Mikkelsen, Tom] Henry Ford Hosp, Hermelin Brain Tumor Ctr, Detroit, MI 48202 USA. [Weiss, Stephanie; Alexander, Brian M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hallisey, Stephen D.; Bochacki, Caelainn A.; Smith, Katrina H.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2011 VL 13 SU 3 BP 86 EP 86 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600349 ER PT J AU Peereboom, DM Mikkelson, T Sloan, AE Rich, JN Supko, JG Ye, XB Brewer, C Lamborn, K Prados, M Grossman, SA AF Peereboom, David M. Mikkelson, Tom Sloan, Andrew E. Rich, Jeremy N. Supko, Jeffrey G. Ye, Xiaobu Brewer, Cathy Lamborn, Kathleen Prados, Michael Grossman, Stuart A. TI A PHASE II AND PHARMACODYNAMIC TRIAL OF RO4929097 FOR PATIENTS WITH RECURRENT/PROGRESSIVE GLIOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Peereboom, David M.; Rich, Jeremy N.; Brewer, Cathy] Cleveland Clin, Cleveland, OH 44106 USA. [Mikkelson, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. [Sloan, Andrew E.] Univ Hosp, Cleveland, OH USA. [Supko, Jeffrey G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ye, Xiaobu; Grossman, Stuart A.] Johns Hopkins Univ, Baltimore, MD USA. [Lamborn, Kathleen] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2011 VL 13 SU 3 BP 86 EP 86 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600350 ER PT J AU Batchelor, T Grossman, S Brem, S Lesser, G Voloschin, A Nabors, LB Mikkelsen, T Desideri, S Supko, J Peereboom, D AF Batchelor, Tracy Grossman, Stuart Brem, Steve Lesser, Glenn Voloschin, Alfredo Nabors, Louis B. Mikkelsen, Tom Desideri, Serena Supko, Jeffrey Peereboom, David TI FEASIBILITY AND PHASE I/II TRIAL OF TANDUTINIB IN PATIENTS WITH RECURRENT GLIOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Batchelor, Tracy; Supko, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grossman, Stuart; Desideri, Serena] Johns Hopkins Univ, Baltimore, MD USA. [Brem, Steve] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Lesser, Glenn] Wake Forest Univ, Winston Salem, NC 27109 USA. [Voloschin, Alfredo] Emory Univ, Atlanta, GA 30322 USA. [Nabors, Louis B.] Univ Alabama, Birmingham, AL USA. [Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. [Peereboom, David] Cleveland Clin, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 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 NOV PY 2011 VL 13 SU 3 BP 89 EP 89 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600360 ER PT J AU Lucas, MR AF Lucas, Michele R. TI HYPERAROUSAL/HYPERVIGILANCE IN PATIENTS WITH BRAIN CANCER CREATES A CYCLE OF SLEEP DISTURBANCE AND DAYTIME SLEEPINESS SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Lucas, Michele R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 121 EP 121 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600476 ER PT J AU Gerard, ME Drappatz, J Muzikansky, A Weiss, S Kesari, S Wong, E Fadul, CE Norden, AD Quant, EC Beroukhim, R Alexander, B Ruland, S Ciampa, AS LaFrankie, DC Sceppa, C Smith, KH Hammond, SN Wen, PY AF Gerard, Mary E. Drappatz, Jan Muzikansky, Alona Weiss, Stephanie Kesari, Santosh Wong, Eric Fadul, Camilo E. Norden, Andrew D. Quant, Eudocia C. Beroukhim, Rameen Alexander, Brian Ruland, Sandra Ciampa, Abigail S. LaFrankie, Debra C. Sceppa, Christine Smith, Katrina H. Hammond, Samantha N. Wen, Patrick Y. TI INTERIM ANALYSIS OF A RANDOMIZED PLACEBO-CONTROLLED PILOT TRIAL OF ARMODAFINIL FOR FATIGUE IN PATIENTS WITH MALIGNANT GLIOMAS UNDERGOING RADIOTHERAPY WITH OR WITHOUT STANDARD CHEMOTHERAPY SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Gerard, Mary E.; Drappatz, Jan; Weiss, Stephanie; Norden, Andrew D.; Quant, Eudocia C.; Beroukhim, Rameen; Alexander, Brian; Ruland, Sandra; Ciampa, Abigail S.; LaFrankie, Debra C.; Sceppa, Christine; Smith, Katrina H.; Hammond, Samantha N.; Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kesari, Santosh] Univ Calif San Diego, San Diego, CA 92103 USA. [Wong, Eric] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Fadul, Camilo E.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 125 EP 125 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600493 ER PT J AU Mahajan, A Grosshans, D McAleer, MF Brown, PD Chintagumpala, M Vats, T Puduvalli, V Yock, T AF Mahajan, Anita Grosshans, David McAleer, Mary Francis Brown, Paul D. Chintagumpala, Murali Vats, Tribhawan Puduvalli, Vinay Yock, Torunn TI A MATCHED COMPARISON OF BLOOD COUNTS DURING WHOLE VERSUS PARTIAL VERTEBRAL PROTON CRANIOSPINAL IRRADIATION SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Mahajan, Anita; Grosshans, David; McAleer, Mary Francis; Brown, Paul D.; Vats, Tribhawan; Puduvalli, Vinay] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Chintagumpala, Murali] Baylor Coll Med, Houston, TX 77030 USA. [Yock, Torunn] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 128 EP 128 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600506 ER PT J AU Wang, CC Floyd, S Chang, CH Warnke, P Chio, CC Kasper, E Mahadevan, A Wong, E Jeyapalan, S Chen, C AF Wang, Che-Chuan Floyd, Scott Chang, Chin-Hong Warnke, Peter Chio, Chung-Ching Kasper, Ekkehard Mahadevan, Anand Wong, Eric Jeyapalan, Suriya Chen, Clark TI CYBERKNIFE HYPOFRACTIONATED STEREOTACTIC RADIOSURGERY (HSRS) OF RESECTION CAVITY AFTER EXCISION OF LARGE CEREBRAL METASTASIS SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Wang, Che-Chuan; Chang, Chin-Hong; Chio, Chung-Ching] Chi Mei Med Ctr, Tainan, Taiwan. [Floyd, Scott; Kasper, Ekkehard; Mahadevan, Anand; Wong, Eric] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Warnke, Peter] Univ Chicago, Chicago, IL 60637 USA. [Jeyapalan, Suriya] Rhode Isl Hosp, Providence, RI USA. [Chen, Clark] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 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 NOV PY 2011 VL 13 SU 3 BP 128 EP 128 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600505 ER PT J AU Colen, RR Mahajan, B Jolesz, FA Zinn, PO AF Colen, Rivka R. Mahajan, Bhanu Jolesz, Ferenc A. Zinn, Pascal O. TI RADIOGENOMIC MAPPING IN GBM IN PATIENTS WITH HIGH VERSUS LOW EDEMA/TUMOR INFILTRATION USING AN IMAGE-GENOMIC ANALYSIS OF 12,764 GENES AND 555 MICRORNAS SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Colen, Rivka R.; Mahajan, Bhanu; Jolesz, Ferenc A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Zinn, Pascal O.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 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 NOV PY 2011 VL 13 SU 3 BP 142 EP 143 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600560 ER PT J AU Chen, C Kasper, E Warnke, P AF Chen, Clark Kasper, Ekkehard Warnke, Peter TI PALLIATIVE ENDOSCOPIC THIRD VENTRICULOSTOMY VERSUS VENTRICULOPERITONEAL SHUNTING IN THE TREATMENT OF OBSTRUCTIVE HYDROCEPHALUS FROM CEREBRAL METASTASIS SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Chen, Clark] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kasper, Ekkehard] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Warnke, Peter] Univ Chicago, Dept Neurosurg, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 155 EP 155 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600610 ER PT J AU Sheth, SA Snuderl, M Kwon, CS Wirth, D Yaroslavsky, A Curry, WT AF Sheth, Sameer A. Snuderl, Matija Kwon, Churl-Su Wirth, Dennis Yaroslavsky, Anna Curry, William T. TI CONFOCAL MICROSCOPIC FLUORESCENCE IMAGING OF GLIOMAS SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Sheth, Sameer A.; Snuderl, Matija; Kwon, Churl-Su; Curry, William T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wirth, Dennis; Yaroslavsky, Anna] Univ Massachusetts, Lowell, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2011 VL 13 SU 3 BP 162 EP 162 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CP UT WOS:000297026600638 ER PT J AU Badr, CE Wurdinger, T Nilsson, J Niers, JM Whalen, M Degterev, A Tannous, BA AF Badr, Christian E. Wurdinger, Thomas Nilsson, Jonas Niers, Johanna M. Whalen, Michael Degterev, Alexei Tannous, Bakhos A. TI Lanatoside C sensitizes glioblastoma cells to tumor necrosis factor-related apoptosis-inducing ligand and induces an alternative cell death pathway SO NEURO-ONCOLOGY LA English DT Article DE cardiac glycoside; glioblastoma; lanatoside C; non-apoptotic cell death; TRAIL ID TRAIL-INDUCED APOPTOSIS; CARDIAC-GLYCOSIDES; CYTOCHROME-C; CANCER-CELLS; DOWN-REGULATION; CULTURED-CELLS; GLIOMA-CELLS; SODIUM-PUMP; IN-VIVO; INHIBITORS AB Human glioblastoma (GBM) cells are notorious for their resistance to apoptosis-inducing therapeutics. We have identified lanatoside C as a sensitizer of GBM cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death partly by upregulation of the death receptor 5. We show that lanatoside C sensitizes GBM cells to TRAIL-induced apoptosis in a GBM xenograft model in vivo. Lanatoside C on its own serves as a therapeutic agent against GBM by activating a caspase-independent cell death pathway. Cells treated with lanatoside C showed necrotic cell morphology with absence of caspase activation, low mitochondrial membrane potential, and early intracellular ATP depletion. In conclusion, lanatoside C sensitizes GBM cells to TRAIL-induced cell death and mitigates apoptosis resistance of glioblastoma cells by inducing an alternative cell death pathway. To our knowledge, this is one of the first examples of use of caspase-independent cell death inducers to trigger tumor regression in vivo. Activation of such mechanism may be a useful strategy to counter resistance of cancer cells to apoptosis. C1 [Badr, Christian E.; Wurdinger, Thomas; Niers, Johanna M.; Whalen, Michael; Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA. [Badr, Christian E.; Wurdinger, Thomas; Niers, Johanna M.; Whalen, Michael; Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA 02129 USA. [Wurdinger, Thomas; Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. [Badr, Christian E.; Wurdinger, Thomas; Niers, Johanna M.; Whalen, Michael; Tannous, Bakhos A.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Badr, Christian E.; Wurdinger, Thomas; Nilsson, Jonas; Niers, Johanna M.] Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. [Degterev, Alexei] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 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 Institutes of Health (NIH)/National Cancer Institute [4R00CA126839]; NIH/National Institute of Neurological Disorders [1R21NS061051, P30 NS045776, 1R01NS064983]; Executive Committee on Research at Massachusetts General Hospital; American Brain Tumor Association FX This work was supported by grants from the National Institutes of Health (NIH)/National Cancer Institute 4R00CA126839, NIH/National Institute of Neurological Disorders 1R21NS061051, P30 NS045776 and 1R01NS064983 (B.A.T.) as well as Executive Committee on Research at Massachusetts General Hospital (C.B.) and the American Brain Tumor Association (T.W.). NR 51 TC 21 Z9 21 U1 1 U2 4 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 NOV PY 2011 VL 13 IS 11 BP 1213 EP 1224 DI 10.1093/neuonc/nor067 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 848CH UT WOS:000297025500006 PM 21757445 ER PT J AU Biffi, A Battey, TWK Ayres, AM Cortellini, L Schwab, K Gilson, AJ Rost, NS Viswanathan, A Goldstein, JN Greenberg, SM Rosand, J AF Biffi, A. Battey, T. W. K. Ayres, A. M. Cortellini, L. Schwab, K. Gilson, A. J. Rost, N. S. Viswanathan, A. Goldstein, J. N. Greenberg, S. M. Rosand, J. TI Warfarin-related intraventricular hemorrhage Imaging and outcome SO NEUROLOGY LA English DT Article ID SPONTANEOUS INTRACEREBRAL HEMORRHAGE; HEMATOMA EXPANSION; THERAPY AB Objective: Oral anticoagulation therapy (OAT) with warfarin increases mortality and disability after intracerebral hemorrhage (ICH), the result of increased ICH volume and risk of hematoma expansion. We investigated whether OAT also influences risk of development of intraventricular hemorrhage (IVH), the volume of IVH and IVH expansion, and whether IVH is a substantive mediator of the overall effect of OAT on ICH outcome. Methods: We performed a retrospective analysis of a prospectively collected single-center cohort of 1,879 consecutive ICH cases (796 lobar, 865 deep, 153 cerebellar, 15 multiple location, 50 primary IVH) from 1999 to 2009. ICH and IVH volumes at presentation, as well as hematoma expansion (>33% or >6 mL increase) and IVH expansion (>2 mL increase), were determined using established semiautomated methods. Outcome was assessed at 90 days using either the modified Rankin Scale or Glasgow Outcome Scale. Results: Warfarin use was associated with IVH risk, IVH volume at presentation, and IVH expansion in both lobar and deep ICH (all p < 0.05) in a dose-response relationship with international normalized ratio. Warfarin was associated with poor outcome in both lobar and deep ICH (p < 0.01), and > 95% of this effect was accounted for by baseline ICH and IVH volumes, as well as ICH and IVH expansion. Conclusion: Warfarin increases IVH volume and risk of IVH expansion in lobar and deep ICH. These findings (along with effects on ICH volume and expansion) likely represent the mechanisms by which anticoagulation worsens ICH functional outcome. Neurology (R) 2011;77:1840-1846 C1 [Biffi, A.; Battey, T. W. K.; Cortellini, L.; Rost, N. S.; Rosand, J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Biffi, A.; Battey, T. W. K.; Ayres, A. M.; Cortellini, L.; Schwab, K.; Gilson, A. J.; Rost, N. S.; Viswanathan, A.; Greenberg, S. M.; Rosand, J.] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Biffi, A.; Battey, T. W. K.; Cortellini, L.; Rost, N. S.; 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. 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 FU National Institute for Neurologic Disorders and Stroke [R01 NS063925, R01 NS059727, P50 NS051343, K23 NS064052, K23 NS059774]; American Heart Association/ Bugher Foundation Centers for Stroke Prevention Research [0775011N, 0755984T]; American Heart Association Bugher Foundation; NIH; NIH/NINDS; NIH (NINDS, NIA); National Stroke Association; American Heart Association-Bugher Foundation; NIH/NIA; CSL Behring; Alzheimer's Association; NIH (NINDS, NHLBI); MGH Deane Institute for Integrative Research in Atrial Fibrillation and Stroke FX Study funding: The authors' work on this study was supported by funding from the National Institute for Neurologic Disorders and Stroke (R01 NS063925, R01 NS059727, P50 NS051343, K23 NS064052, K23 NS059774). Dr. Biffi received support from the American Heart Association/ Bugher Foundation Centers for Stroke Prevention Research (0775011N, 0755984T). Funding entities had no involvement in study design, data collection, analysis, and interpretation, writing of the report, and in the decision to submit the paper for publication.; Dr. Biffi receives research support from the American Heart Association Bugher Foundation. T. W. K. Battey reports no disclosures. A. M. Ayres receives research support from the NIH. L. Cortellini receives research support from the NIH/NINDS. K. M. Schwab receives research support from the NIH (NINDS, NIA). A.J. Gilson reports no disclosures. Dr. Rost serves as Associate Editor for Frontiers in Hospitalist Neurology and Assistant Editor for Stroke and receives research support from the NIH/NINDS, the National Stroke Association, and the American Heart Association-Bugher Foundation. Dr. Viswanathan has served as consultant for Athena Diagnostics, Inc. and receives research support from the NIH/NIA. Dr. Goldstein serves on a scientific advisory board for and received funding for travel and consulting honoraria from CSL Behring; serves as an Associate Editor for Academic Emergency Medicine and 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 16 TC 26 Z9 27 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 2011 VL 77 IS 20 BP 1840 EP 1846 DI 10.1212/WNL.0b013e3182377e12 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 849WS UT WOS:000297156700018 PM 22049204 ER PT J AU Perez, DL Larvie, M Acar, D Daffner, K AF Perez, D. L. Larvie, M. Acar, D. Daffner, K. TI Teaching NeuroImages: Apathetic variant of frontotemporal dementia SO NEUROLOGY LA English DT Editorial Material C1 [Perez, D. L.; Acar, D.; Daffner, K.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Perez, D. L.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Perez, D. L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Larvie, M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Perez, DL (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM david.lperez@gmail.com 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 NOV PY 2011 VL 77 IS 20 BP E117 EP E117 DI 10.1212/WNL.0b013e3182377e4c PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 849WS UT WOS:000297156700001 PM 22084280 ER PT J AU Bley, AE Giannikopoulos, OA Hayden, D Kubilus, K Tifft, CJ Eichler, FS AF Bley, Annette E. Giannikopoulos, Ourania A. Hayden, Doug Kubilus, Kim Tifft, Cynthia J. Eichler, Florian S. TI Natural History of Infantile G(M2) Gangliosidosis SO PEDIATRICS LA English DT Article DE infantile G(M2) gangliosidosis; natural history; Tay Sachs; Sandhoff; survival; lysosomal disorders; neurodegeneration ID TAY-SACHS-DISEASE; HEXOSAMINIDASE ALPHA-GENE; SANDHOFF DISEASE; NEUTRAL GLYCOSPHINGOLIPIDS; GM2 GANGLIOSIDOSIS; GENERALIZED ACCUMULATION; FINE-STRUCTURE; BRAIN; STORAGE; MUTATION AB OBJECTIVE: GM2 gangliosidoses are caused by an inherited deficiency of lysosomal beta-hexosaminidase and result in ganglioside accumulation in the brain. Onset during infancy leads to rapid neurodegeneration and death before 4 years of age. We set out to quantify the rate of functional decline in infantile GM2 gangliosidosis on the basis of patient surveys and a comprehensive review of existing literature. METHODS: Patients with infantile GM2 gangliosidosis (N = 237) were surveyed via questionnaire by the National Tay Sachs & Allied Diseases Association (NTSAD). These data were supplemented by survival data from the NTSAD database and a literature survey. Detailed retrospective surveys from 97 patients were available. Five patients who had received hematopoietic stem cell transplantation were evaluated separately. The mortality rate of the remaining 92 patients was comparable to that of the 103 patients from the NTSAD database and 121 patients reported in the literature. RESULTS: Common symptoms at onset were developmental arrest (83%), startling (65%), and hypotonia (60%). All 55 patients who had learned to sit without support lost that ability within 1 year. Individual functional measures correlated with each other but not with survival. Gastric tube placement was associated with prolonged survival. Tay Sachs and Sandhoff variants did not differ. Hematopoietic stem cell transplantation was not associated with prolonged survival. CONCLUSIONS: We studied the timing of regression in 97 cases of infantile GM2 gangliosidosis and conclude that clinical disease progression does not correlate with survival, likely because of the impact of improved supportive care over time. However, functional measures are quantifiable and can inform power calculations and study design of future interventions. Pediatrics 2011; 128: e1233-e1241 C1 [Bley, Annette E.; Giannikopoulos, Ourania A.; Eichler, Florian S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hayden, Doug] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Kubilus, Kim] Natl Tay Sachs & Allied Dis Assoc, Boston, MA USA. [Tifft, Cynthia J.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Eichler, FS (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,ACC 708, Boston, MA 02114 USA. EM feichler@partners.org FU Harvard Catalyst/Harvard Clinical and Translational Science Center (National Institutes of Health) [UL1 RR 025758]; Harvard University; National Institutes of Health [K08NS52550]; National Institutes of Health "Lysosomal Disease Network" [5U54NS065768]; NTSAD FX This work was conducted with support from Harvard Catalyst/Harvard Clinical and Translational Science Center (National Institutes of Health award UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers), National Institutes of Health training grant K08NS52550 (to Dr Eichler), and National Institutes of Health "Lysosomal Disease Network" grant 5U54NS065768. Ms. Giannikopoulos, Mrs. Kubilus, and Dr. Eichler were supported by the NTSAD. NR 76 TC 26 Z9 29 U1 1 U2 12 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2011 VL 128 IS 5 BP E1233 EP E1241 DI 10.1542/peds.2011-0078 PG 9 WC Pediatrics SC Pediatrics GA 843YO UT WOS:000296714000024 PM 22025593 ER PT J AU Schinka, JA Casey, RJ Kasprow, W Rosenheck, RA AF Schinka, John A. Casey, Roger J. Kasprow, Wesley Rosenheck, Robert A. TI Requiring Sobriety at Program Entry: Impact on Outcomes in Supported Transitional Housing for Homeless Veterans SO PSYCHIATRIC SERVICES LA English DT Article ID 1ST AB Objective: An important distinction in models of housing for the homeless is whether programs that require abstinence prior to program admission produce better outcomes than unrestricted programs. Data from a large transitional housing program were used to compare client characteristics of and outcomes from programs requiring abstinence at admission and programs not requiring abstinence. Methods: The U.S. Department of Veterans Affairs (VA) Northeast Program Evaluation Center provided records of individuals who were admitted into, and discharged from, the VA Grant and Per Diem program in 2003-2005. Records contained information from intake interviews, program discharge information, and descriptions of provider characteristics. Analyses were based on 3,188 veteran records, 1,250 from programs requiring sobriety at admission and 1,938 from programs without a sobriety requirement. Group differences were examined with t tests and chi square analyses; predictors of program outcome were determined with logistic regression. Results: Individuals using drugs or alcohol at program admission had more problematic histories, as indicated by several general health and mental health variables, and shorter program stays. There were significant differences between groups in the frequency of program completion, recidivism for homelessness, and employment on program discharge, but effect sizes for these analyses were uniformly small and of questionable importance. Regression analyses did not find meaningful support for the importance of sobriety on program entry on any of the outcome measures. Conclusions: The results add evidence to the small body of literature supporting the position that sobriety on program entry is not a critical variable in determining outcomes for individuals in transitional housing programs. (Psychiatric Services 62:1325-1330, 2011) C1 [Schinka, John A.; Casey, Roger J.] Natl Ctr Homelessness Vet, Tampa, FL 33612 USA. [Kasprow, Wesley] US Dept Vet Affairs, NE Program Evaluat Ctr, West Haven, CT USA. [Rosenheck, Robert A.] Yale Univ, Dept Psychiat, West Haven, CT USA. RP Schinka, JA (reprint author), Natl Ctr Homelessness Vet, MHBS 116B,13000 BB Downs Blvd, Tampa, FL 33612 USA. EM jschinka@health.usf.edu RI McCarthy, Jodie/B-5760-2012 FU VA National Center on Homelessness Among Veterans FX This research was supported by the VA National Center on Homelessness Among Veterans. NR 11 TC 5 Z9 5 U1 0 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD NOV PY 2011 VL 62 IS 11 BP 1325 EP 1330 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 843LT UT WOS:000296674000012 PM 22211212 ER PT J AU Kim, HM Pfeiffer, P Ganoczy, D Valenstein, M AF Kim, Hyungjin Myra Pfeiffer, Paul Ganoczy, Dara Valenstein, Marcia TI Intensity of Outpatient Monitoring After Discharge and Psychiatric Rehospitalization of Veterans With Depression SO PSYCHIATRIC SERVICES LA English DT Article ID SUBSTANCE USE DISORDERS; HOSPITALIZATION; PREDICTORS; SUICIDE; RISK; CARE AB Objective: This study assessed whether increased frequency of clinical monitoring during the high-risk period of 12 weeks after discharge from a psychiatric hospitalization reduced subsequent rehospitalization in a national cohort of Veterans Health Administration patients receiving depression treatment between 1999 and 2004. Methods: A case-control design was used. Patients who had at least two inpatient psychiatric hospitalizations were identified (case group, N=17,852) and then individually matched with up to two patients who also had been discharged from psychiatric inpatient settings but were not rehospitalized for the number of days between the case-group patient's discharge and subsequent rehospitalization (N=35,511). Results: Covariate-adjusted relative risk (RR) did not show an association between increased monitoring and subsequent psychiatric hospitalization, but there was a significant negative interaction between monitoring and a comorbid substance use disorder diagnosis (p<.001). Increased monitoring was positively associated with rehospitalization of patients without a substance use disorder, whereas increased monitoring was not associated with increased risk of rehospitalization of those with a comorbid substance use disorder. The RR of rehospitalization associated with a weekly monitoring visit (12 visits per 84 days) versus no monitoring visit was 1.14 for patients without a substance use disorder, whereas the RR was reduced to .94 for patients with a substance use disorder. Conclusions: Increased outpatient monitoring during the high-risk period after discharge appears to have a modest protective effect on rehospitalization among depressed patients with a comorbid substance use disorder. (Psychiatric Services 62:1346-1352, 2011) C1 [Kim, Hyungjin Myra] Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA. [Kim, Hyungjin Myra; Pfeiffer, Paul; Ganoczy, Dara; Valenstein, Marcia] US Dept Vet Affairs, Serious Mental Illness Treatment Resource & Evalu, Ann Arbor Ctr Excellence, Ann Arbor, MI USA. [Pfeiffer, Paul; Valenstein, Marcia] Univ Michigan, Dept Psychianj, Ann Arbor, MI 48109 USA. RP Kim, HM (reprint author), Univ Michigan, Ctr Stat Consultat & Res, 3550 Rackham,915 E Washington St, Ann Arbor, MI 48109 USA. EM myrakim@umich.edu FU U.S. Department of Veterans Affairs, Health Services Research and Development Service [IIR 04-211-1, MRP 03-320]; National Institute of Mental Health [R01-MH078698-01] FX The funding sources for this work were grants IIR 04-211-1 and MRP 03-320 from the U.S. Department of Veterans Affairs, Health Services Research and Development Service, and grant R01-MH078698-01 from the National Institute of Mental Health. Resources were also contributed by the Serious Mental Illness Treatment Resource and Evaluation Center, Ann Arbor. NR 19 TC 10 Z9 10 U1 2 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD NOV PY 2011 VL 62 IS 11 BP 1346 EP 1352 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 843LT UT WOS:000296674000015 PM 22211215 ER PT J AU Nicolson, SE Chabon, B Larsen, KA Kelly, SE Potter, AW Stern, TA AF Nicolson, Stephen E. Chabon, Brenda Larsen, Kenneth A. Kelly, Susan E. Potter, Adam W. Stern, Theodore A. TI Primitive Reflexes Associated with Delirium: A Prospective Trial SO PSYCHOSOMATICS LA English DT Article ID POSTOPERATIVE DELIRIUM; VASCULAR DEMENTIA; OLDER-PEOPLE; DISEASE; SIGNS; ADULTS; HEALTHY AB Background: The presence of primitive reflexes (PRs) may have diagnostic or prognostic value in the evaluation of cognitive impairment. Objective: We hypothesized that the presence of preoperative PRs would predict the development of postoperative delirium and that the emergence of PRs postoperatively would be positively associated with the emergence of delirium. Methods: Patients participating in a larger study on the prophylaxis of postoperative delirium were evaluated for the presence of six PRs (grasp reflex [left and right], palmomental reflex [left and right], glabellar tap, and snout reflex), preoperatively and postoperatively The presence of PRs was then correlated with the development of delirium. Results: Of the 79 patients studied, 29% (n = 23) developed delirium during the postoperative period. The preoperative presence of one PR did not predict the development of delirium, but the only patient with > 1 PR preoperatively went on to develop delirium in the postoperative period. Similarly, having one frontal release sign in the postoperative period did not correlate with delirium, while the appearance of more than one PR was associated with a greater likelihood of delirium. Of the 11 patients who had two or more frontal release signs during one postoperative examination, six (55%) developed delirium. Of the five patients who showed three or more frontal release signs, 4 (80%) developed delirium. Conclusion: Our study is the first to investigate the relationship between the appearance of PRs and the development of delirium. We have provided some evidence that PRs are associated with acute CNS dysfunction. (Psychosomatics 2011; 52:507-512) C1 [Nicolson, Stephen E.; Chabon, Brenda] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA. [Larsen, Kenneth A.; Kelly, Susan E.; Potter, Adam W.] New England Baptist Hosp, Dept Med, Boston, MA USA. [Kelly, Susan E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kelly, Susan E.] Tufts Med Ctr, Dept Med, Boston, MA USA. [Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Nicolson, SE (reprint author), Montefiore Med Ctr, Dept Psychiat, 111 E 210 St, Bronx, NY 10467 USA. EM snicolso@montefiore.org RI Potter, Adam/D-9893-2014; OI Potter, Adam/0000-0003-4980-8353 NR 33 TC 4 Z9 5 U1 0 U2 3 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 NOV-DEC PY 2011 VL 52 IS 6 BP 507 EP 512 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 849PJ UT WOS:000297137300002 PM 22054619 ER PT J AU Chang, BH Dusek, JA Benson, H AF Chang, Bei-Hung Dusek, Jeffery A. Benson, Herbert TI Psychobiological Changes from Relaxation Response Elicitation: Long-Term Practitioners vs. Novices SO PSYCHOSOMATICS LA English DT Article ID TRANSCENDENTAL-MEDITATION PROGRAM; QUALITY-OF-LIFE; STRESS REDUCTION; PSYCHOSOCIAL STRESS; AFRICAN-AMERICANS; BREAST-CANCER; DEPRESSION; CORTISOL; MODEL; METAANALYSIS AB Objective: The relaxation response (RR) is a physiological state that is the counterpart to the stress response. We investigate the psychological and biological effects, as well as the correlation between these two effects that are associated with short-term vs. long-term practice of techniques that elicit the RR ("RR practice"). Methods: The study comprised both a cross sectional and an 8-week prospective design. The study sample included individuals with a long-term RR practice ("long-term practitioners" n = 28) and those with no prior RI? practice experience ("novices" n = 28). The novices received 8 weeks of RR-elicitation training ("RR training") for the prospective analysis (short-term practice). Results: Long-term practitioners reported lower levels of psychological distress than the novices before they received RR training. As a result of the 8-week RR training, novices significantly reduced their psychological distress to levels comparable to that of long-term practitioners. Long-term practitioners had greater immediate (after listening to a RR-eliciting CD) decreases in psychological distress level than the 8-week trained novices. Furthermore, the reduction in psychological distress levels for long-term practitioners correlated with a reduction in biological measures of stress, after controlling for baseline values. There was no reduction in biological measures and no correlation with psychological measures in the 8-week trained novices. Conclusions: While our data indicate that even a short-term 8-week RR-eliciting practice can decrease psychological distress levels, only after years of RR practice does psychological distress reduction coincide with biological change. (Psychosomatics 2011; 52:550-559) C1 [Chang, Bei-Hung] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Chang, Bei-Hung] VA Boston Hlth Care Syst, Boston, MA USA. [Dusek, Jeffery A.; Benson, Herbert] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Dusek, Jeffery A.] Abbott NW Hosp, Penny George Inst Hlth & Healing, Minneapolis, MN 55407 USA. RP Chang, BH (reprint author), 150 S Huntington Ave,152H,Bldg 9,4th Floor, Boston, MA 02130 USA. EM bhchang@bu.edu OI Dusek, Jeffery/0000-0001-9581-0564 FU Center for Disease Control and Prevention [5 R01 DP000339, H75/CCH119124, H75/CCH123424] FX The study was funded by the Center for Disease Control and Prevention: grant numbers 5 R01 DP000339, H75/CCH119124, and H75/CCH123424. The authors disclosed no proprietary or commercial interest in any product mentioned or concept discussed in this article. NR 39 TC 12 Z9 12 U1 3 U2 15 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 NOV-DEC PY 2011 VL 52 IS 6 BP 550 EP 559 PG 10 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 849PJ UT WOS:000297137300008 PM 22054625 ER PT J AU Beach, SR Stern, TA AF Beach, Scott R. Stern, Theodore A. TI "Playing Possum:" Differential Diagnosis, Work-Up, and Treatment of Profound Interpersonal Withdrawal SO PSYCHOSOMATICS LA English DT Article AB Patients who exhibit profound interpersonal withdrawal 1 challenge clinicians in terms of diagnostic formulation, elucidation of the etiology or mechanism of disease, and treatment. Insufficient history provided directly by the patient leads to a greater reliance on the physical examination and a need for heightened recognition of consistencies and inconsistencies in presenting signs and symptoms. Strategies to establish the potential causes and to refine the appropriate work-up are crucial for clinicians who care for such complex patients. We present two case vignettes to highlight the differential diagnosis, the mechanisms of disease, and the potential treatments of patients who appear to be "playing possum" (a term that refers to the instinctive defense mechanism exhibited by the Virginia opossum [involving inertia, rigidity, drooling, and release of anal gland fluid] in the face of threat).(1) C1 [Beach, Scott R.; Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Beach, Scott R.; Stern, Theodore A.] Harvard Univ, Sch Med, 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 5 TC 2 Z9 2 U1 0 U2 1 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 NOV-DEC PY 2011 VL 52 IS 6 BP 560 EP 562 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 849PJ UT WOS:000297137300009 PM 22054626 ER PT J AU Mendez, MF Ramirez-Bermudez, J AF Mendez, Mario F. Ramirez-Bermudez, Jesus TI Cotard Syndrome in Semantic Dementia SO PSYCHOSOMATICS LA English DT Article ID DELUSIONS; BRAIN C1 [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. [Ramirez-Bermudez, Jesus] Natl Inst Neurol & Neurosurg Mexico, Dept Neuropsychiat, Mexico City, DF, Mexico. RP Mendez, MF (reprint author), VA Greater Angeles, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu FU [R01AG034499-03] FX This work was funded and supported by #R01AG034499-03 NR 17 TC 8 Z9 8 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 NOV-DEC PY 2011 VL 52 IS 6 BP 571 EP 574 PG 4 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 849PJ UT WOS:000297137300012 PM 22054629 ER PT J AU Horan, WP Kring, AM Gur, RE Reise, SP Blanchard, JJ AF Horan, William P. Kring, Ann M. Gur, Raquel E. Reise, Steven P. Blanchard, Jack J. TI Development and psychometric validation of the Clinical Assessment Interview for Negative Symptoms (CAINS) SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Rating scale; Expression; Experience; Negative symptoms; Clinical trials ID PSYCHIATRIC RATING-SCALE; SCHIZOPHRENIA; DEFICITS AB Progress in the development of new pharmacological and psychosocial treatments for the negative symptoms of schizophrenia is impeded by limitations of available assessment instruments. The multi-site Collaboration to Advance Negative Symptom Assessment in Schizophrenia (CANSAS) was established to develop and validate a new clinical rating scale using a transparent, iterative, and data-driven process. The Clinical Assessment Interview for Negative Symptoms (CAINS) was designed to address limitations of existing measures and assess consensus-based sub-domains, including asociality, avolition, anhedonia, affective blunting, and alogia. The structure and psychometric properties of the CAINS were evaluated in a sample of 281 schizophrenia and schizoaffective outpatients at four sites. Converging structural analyses indicated that the scale was comprised of two moderately correlated factors one reflecting experiential impairments (diminished motivation and enjoyment of social, vocational, and recreational activities) and one reflecting expressive impairments (diminished non-verbal and verbal communication). Item-level analyses revealed generally good distributional properties, inter-rater agreement, discriminating anchor points, and preliminary convergent and discriminant validity. Results indicate that the CAINS is a promising new measure for quantifying negative symptoms in clinical neuroscience and treatment studies, Results guided item modification or deletion, and the reliability and validity of the revised, shorter version of the CAINS is in the final phase of development within the CANSAS project. Published by Elsevier B.V. C1 [Horan, William P.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Kring, Ann M.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Gur, Raquel E.] Univ Penn, Philadelphia, PA 19104 USA. [Blanchard, Jack J.] Univ Maryland, College Pk, MD 20742 USA. RP Horan, WP (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, VA Greater Los Angeles Healthcare Syst, 300 UCLA Med Plaza,Suite 2255, Los Angeles, CA 90095 USA. EM horan@ucla.edu FU National Institute of Mental Health [K02-MH079231, R01-MH082839, RO1-MH082890, R01-MH082782, R01-MH82783] FX This work was supported by the National Institute of Mental Health (K02-MH079231 and R01-MH082839 to JJB: RO1-MH082890 to AMK: R01-MH082782 to WPH; and R01-MH82783 to REG). Funding sources had no role in study design or in the collection, analysis and interpretation of data; or in the writing of this report. NR 32 TC 83 Z9 83 U1 4 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV PY 2011 VL 132 IS 2-3 BP 140 EP 145 DI 10.1016/j.schres.2011.06.030 PG 6 WC Psychiatry SC Psychiatry GA 848ZB UT WOS:000297092500008 PM 21798716 ER PT J AU Meszaros, ZS Dimmock, JA Ploutz-Snyder, R Chauhan, SVS Abdul-Malak, Y Middleton, FA Batki, SL AF Meszaros, Zsuzsa Szombathyne Dimmock, Jacqueline A. Ploutz-Snyder, Robert Chauhan, Sumerendra Vir Singh Abdul-Malak, Ynesse Middleton, Frank A. Batki, Steven L. TI Accuracy of self-reported medical problems in patients with alcohol dependence and co-occurring schizophrenia or schizoaffective disorder SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Alcohol; Schizophrenia; Schizoaffective disorder; Medical illness; Self-report ID MENTAL-DISORDERS; UNITED-STATES; COMORBIDITY; CARE; MORBIDITY; MORTALITY; ILLNESS; PEOPLE; HEALTH; SCALE AB Background: Schizophrenia and alcohol dependence (AD) are both major risk factors for a variety of medical problems, yet little is known about the medical status of patients in whom both conditions coexist. Objective: The objectives of this study are to assess accuracy of self-reported medical problems and to compare the accuracy reports in patients with schizophrenia or schizoaffective disorder and co-occurring AD compared to patients with AD only and to controls. Our hypothesis was that medical problems are under-reported in patients with co-occurring disorders, possibly due to the combination of alcohol use and symptoms of schizophrenia. Methods: Self-reported medical diagnoses were recorded and compared to medical records obtained from all area hospitals in 42 patients with schizophrenia and AD, 44 patients with schizoaffective disorder and AD, 41 patients with AD only, and 15 control subjects. Patients underwent medical history, physical examination, and review of medical records. Results: Patients with schizophrenia or schizoaffective disorder and co-occurring AD underreported their medical problems significantly more than patients with AD only and controls. Accuracy of self report was significantly lower in patients with schizophrenia-spectrum disorders plus co-occurring alcohol dependence than in AD alone or in controls. The most commonly underreported diagnoses included coronary artery disease, chronic renal failure, seizure disorder, hyperlipidemia, asthma and hypertension. Discussion: In order to detect potentially unreported medical conditions in patients with co-occurring schizophrenia/schizoaffective disorder and alcohol dependence, the use of targeted screening questionnaires is recommended in addition to physical examination and thorough review of medical records. (C) 2011 Elsevier B.V. All rights reserved. C1 [Meszaros, Zsuzsa Szombathyne; Dimmock, Jacqueline A.; Chauhan, Sumerendra Vir Singh; Abdul-Malak, Ynesse; Batki, Steven L.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Ploutz-Snyder, Robert] NASA, Univ Space Res Assoc, Houston, TX USA. [Middleton, Frank A.] SUNY Upstate Med Univ, Dept Neurosci Physiol, Syracuse, NY 13210 USA. [Batki, Steven L.] UCSF, Dept Psychiat, San Francisco, CA USA. [Batki, Steven L.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Meszaros, ZS (reprint author), SUNY Upstate Med Univ, Dept Psychiat, 750 E Adams St, Syracuse, NY 13210 USA. EM meszaroz@upstate.edu FU NIH-NIAAA [RO1 AA01365501, RO1 AA01615103] FX This research was supported by NIH-NIAAA grant RO1 AA01365501, "Naltrexone Treatment of Alcohol Abuse in Schizophrenia" (PI: Batki) and by NIH-NIAAA grant RO1 AA01615103 "Peripheral Pathophysiogenomic Markers of Ethanol-induced Brain Damage" (PI: Middleton). The NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit this paper for publication. NR 32 TC 3 Z9 3 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV PY 2011 VL 132 IS 2-3 BP 190 EP 193 DI 10.1016/j.schres.2011.07.033 PG 4 WC Psychiatry SC Psychiatry GA 848ZB UT WOS:000297092500016 PM 21852074 ER PT J AU Selim, M Yeatts, S Goldstein, JN Gomes, J Greenberg, S Morgenstern, LB Schlaug, G Torbey, M Waldman, B Xi, GH Palesch, Y AF Selim, Magdy Yeatts, Sharon Goldstein, Joshua N. Gomes, Joao Greenberg, Steven Morgenstern, Lewis B. Schlaug, Gottfried Torbey, Michel Waldman, Bonnie Xi, Guohua Palesch, Yuko CA The Deferoxamine Mesylate In Intra TI Safety and Tolerability of Deferoxamine Mesylate in Patients With Acute Intracerebral Hemorrhage SO STROKE LA English DT Article DE deferoxamine mesylate; iron; ICH ID PERIHEMATOMAL EDEMA; BRAIN EDEMA; NATURAL-HISTORY; BLOOD-PRESSURE; AGED RATS; IRON; HEMATOMA; INJURY; EXPRESSION; FERRITIN AB Background and Purpose-Treatment with the iron chelator, deferoxamine mesylate (DFO), improves neurological recovery in animal models of intracerebral hemorrhage (ICH). We aimed to evaluate the feasibility, safety, and tolerability of varying dose-tiers of DFO in patients with spontaneous ICH, and to determine the maximum tolerated dose to be adopted in future efficacy studies. Methods-This was a multicenter, phase-I, dose-finding study using the Continual Reassessment Method. DFO was administered by intravenous infusion for 3 consecutive days, starting within 18 hours of ICH onset. Subjects underwent repeated clinical assessments through 90 days, and computed tomography neuroimaging pre- and post-drug-administration. Results-Twenty subjects were enrolled onto 5 dose tiers, starting with 7 mg/kg per day and ending with 62 mg/kg per day as the maximum tolerated dose. Median age was 68 years (range, 50-90); 60% were men; and median Glasgow Coma Scale and National Institutes of Health Stroke Scale scores on admission were 15 (5-15) and 9 (0-39), respectively. ICH location was lobar in 40%, deep in 50%, and brain stem in 10%; intraventricular hemorrhage was present in 15%. DFO was discontinued because of adverse events in 2 subjects (10%). Six subjects (30%) experienced 12 serious adverse events, none of which were drug-related. DFO infusions were associated with mild blood-pressure-lowering effects. Fifty percent of patients had modified Rankin scale scores <= 2, and 39% had modified Rankin scale scores of 4 to 6 on day 90; 15% died. Conclusions-Consecutive daily infusions of DFO after ICH are feasible, well-tolerated, and not associated with excessive serious adverse events or mortality. Our findings lay the groundwork for future studies to evaluate the efficacy of DFO in ICH. (Stroke. 2011; 42:3067-3074.) C1 [Selim, Magdy; Schlaug, Gottfried] Harvard Univ, Beth Israel Deaconess Med Ctr, Stroke Div, Dept Neurol,Med Sch, Boston, MA 02215 USA. [Yeatts, Sharon; Waldman, Bonnie; Palesch, Yuko] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Goldstein, Joshua N.; Greenberg, Steven] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Goldstein, Joshua N.; Greenberg, Steven] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Morgenstern, Lewis B.; Xi, Guohua] Univ Michigan, Stroke Program, Ann Arbor, MI 48109 USA. [Morgenstern, Lewis B.; Xi, Guohua] Univ Michigan, Dept Neurosurg, Ann Arbor, MI 48109 USA. [Gomes, Joao] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Torbey, Michel] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. [Torbey, Michel] Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA. RP Selim, M (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Stroke Div, Dept Neurol,Med Sch, 330 Brookline Ave Palmer 127, Boston, MA 02215 USA. EM mselim@bidmc.harvard.edu RI Goldstein, Joshua/H-8953-2016 FU NIH/NINDS [1R01-NS 057127]; NINDS [1R01-NS 057127, U01 NS052510] FX The study was sponsored by the NIH/NINDS (1R01-NS 057127). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.; All investigators received modest support from the NINDS (1R01-NS 057127). Dr. Selim received significant support as the Principal Investigator. L.B.M. and G.X. received additional significant support from the NINDS (U01 NS052510). NR 33 TC 48 Z9 51 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2011 VL 42 IS 11 BP 3067 EP U237 DI 10.1161/STROKEAHA.111.617589 PG 24 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 842EM UT WOS:000296574500249 PM 21868742 ER PT J AU Carandang, RA Barton, B Rordorf, GA Ogilvy, CS Sims, JR AF Carandang, Raphael A. Barton, Bruce Rordorf, Guy A. Ogilvy, Christopher S. Sims, John R. TI Nicotine Replacement Therapy After Subarachnoid Hemorrhage Is Not Associated With Increased Vasospasm SO STROKE LA English DT Article DE neurocritical care; nicotine; subarachnoid hemorrhage; vascular tone regul; vasospasm ID ALPHA(7)-NICOTINIC ACETYLCHOLINE-RECEPTORS; RATS IN-VIVO; CIGARETTE-SMOKING; NEUROGENIC VASODILATION; TRANSDERMAL NICOTINE; BASILAR ARTERY; RISK-FACTORS; MECHANISMS; NEUROPROTECTION; DEFINITION AB Background and Purpose-A significant number of patients with aneurysmal subarachnoid hemorrhage are active smokers and at risk for acute nicotine withdrawal. There is conflicting literature regarding the vascular effects of nicotine and theoretical concern that it may worsen vasospasm. The literature on the safety of nicotine replacement therapy and its effects on vasospasm is limited. Methods-A retrospective analysis was conducted of a prospectively collected database of aneurysmal subarachnoid hemorrhage patients admitted to the neurointensive care unit from 1994 to 2008. Paired control subjects matched for age, sex, Fisher score, aneurysm size and number, hypertension, and current medication were analyzed. The primary outcome was clinical and angiographic vasospasm and the secondary outcome was Glasgow Outcome Score on discharge. Conditional logistic models were used to investigate univariate and multivariate relationships between predictors and outcome. Results-Two hundred fifty-eight active smoking patients were included of which 87 were treated with transdermal nicotine replacement therapy. Patients were well matched for age, sex, gender, Fisher score, aneurysm size and number, hypertension, and current medications, but patients who received nicotine replacement therapy had less severe Hunt-Hess scores and Glasgow coma scores. There was no difference in angiographic vasospasm, but patients who received nicotine replacement therapy were less likely to have clinical vasospasm (19.5 versus 32.8%; P=0.026) and a Glasgow Outcome Score <4 on discharge (62.6% versus 81.6%; P=0.005) on multivariate analysis. Conclusions-Nicotine replacement therapy was not associated with increased angiographic vasospasm and was associated with less clinical vasospasm and better Glasgow Outcome Score scores on discharge. (Stroke. 2011;42:3080-3086.) C1 [Carandang, Raphael A.] Univ Massachusetts, Sch Med, Dept Neurol, UMASS Mem Med Ctr, Worcester, MA USA. [Barton, Bruce] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, UMASS Mem Med Ctr, Worcester, MA USA. [Rordorf, Guy A.; Sims, John R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Rordorf, Guy A.; Ogilvy, Christopher S.; Sims, John R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Rordorf, Guy A.; Sims, John R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Carandang, RA (reprint author), 55 Lake Ave N, Worcester, MA 01655 USA. EM raphael.carandang@umassmemorial.org OI Barton, Bruce/0000-0001-7878-8895 FU National Institutes of Health [K08NS049241]; Eli Lilly FX J.R.S. is supported by National Institutes of Health K08NS049241.; J.R.S. is currently employed by Eli Lilly and receives salary and stock as compensation. NR 29 TC 2 Z9 2 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 NOV PY 2011 VL 42 IS 11 BP 3080 EP 3086 DI 10.1161/STROKEAHA.111.620955 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 842EM UT WOS:000296574500251 PM 21868740 ER PT J AU Smith, EE Fonarow, GC Reeves, MJ Cox, M Olson, DM Hernandez, AF Schwamm, LH AF Smith, Eric E. Fonarow, Gregg C. Reeves, Mathew J. Cox, Margueritte Olson, DaiWai M. Hernandez, Adrian F. Schwamm, Lee H. TI Outcomes in Mild or Rapidly Improving Stroke Not Treated With Intravenous Recombinant Tissue-Type Plasminogen Activator Findings From Get With The Guidelines-Stroke SO STROKE LA English DT Article DE acute stroke; thrombolysis; outcomes ID TRANSIENT ISCHEMIC ATTACK; PERIPHERAL VASCULAR-DISEASE; CARDIOVASCULAR RADIOLOGY; SCIENTIFIC STATEMENT; EARLY MANAGEMENT; ASSOCIATION; COUNCIL; CARE; INTERVENTION; ELIGIBILITY AB Background and Purpose-Mild or rapidly improving stroke is a frequently cited reason for not giving intravenous recombinant tissue-type plasminogen activator (rtPA), but some of these patients may have poor outcomes. We used data from a large nationwide study (Get With The Guidelines-Stroke) to determine risk factors for poor outcomes after mild or improving stroke at hospital discharge. Methods-Between 2003 and 2009, there were 29 200 ischemic stroke patients (from 1092 hospitals) arriving within 2 hours after symptom onset with mild or rapidly improving stroke symptoms as the only contraindication to rtPA. Logistic regression was used to determine the independent predictors of discharge to home. Results-Among 93 517 patients arriving within 2 hours, 31.2% (29 200) did not receive rtPA solely because of mild/improving stroke. Among the 29 200 mild/improving cases, 28.3% were not discharged to home, and 28.5% were unable to ambulate without assistance at hospital discharge. The likelihood of home discharge was strongly related to initial National Institutes of Health Stroke Scale score (P<0.001). In multivariable-adjusted analysis, patients not discharged to home were more likely to be older, female, and black; have a higher National Institutes of Health Stroke Scale score and vascular risk factors; and were less likely to be taking lipid-lowering medication before admission. Conclusions-In this large, nationwide study, a sizeable minority of patients who did not receive intravenous rtPA solely because of mild/improving stroke had poor short-term outcomes, raising the possibility that stroke-related disability is relatively common, even in "mild" stroke. A controlled trial of reperfusion therapy in this population may be warranted. (Stroke. 2011;42:3110-3115.) C1 [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Hotchkiss Brain Inst, Calgary, AB, Canada. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Cox, Margueritte; Olson, DaiWai M.; Hernandez, Adrian F.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Smith, EE (reprint author), Foothills Med Ctr, Room C1212,1403 29 St NW, Calgary, AB T2N 2T9, Canada. EM eesmith@ucalgary.ca RI Hernandez, Adrian F./A-7818-2016; OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616; Smith, Eric/0000-0003-3956-1668 FU Bristol-Myers Squib/Sanofi Pharmaceutical; American Heart Association Pharmaceutical Roundtable; Boehringer-Ingelheim; GWTG-Stroke FX The GWTG-Stroke program is provided by the American Heart Association/American Stroke Association. The GWTG-Stroke program is currently supported in part by a charitable contribution from Bristol-Myers Squib/Sanofi Pharmaceutical Partnership and the American Heart Association Pharmaceutical Roundtable. GWTG-Stroke has been funded in the past through support from Boehringer-Ingelheim and Merck. NR 16 TC 84 Z9 90 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 NOV PY 2011 VL 42 IS 11 BP 3110 EP U309 DI 10.1161/STROKEAHA.111.613208 PG 17 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 842EM UT WOS:000296574500256 PM 21903949 ER PT J AU Paramsothy, P Knopp, RH Kahn, SE Retzlaff, BM Fish, B Ma, LN Ostlund, RE AF Paramsothy, Pathmaja Knopp, Robert H. Kahn, Steven E. Retzlaff, Barbara M. Fish, Brian Ma, Lina Ostlund, Richard E., Jr. TI Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; DIETARY-CHOLESTEROL; MASS-SPECTROMETRY; SENSITIVITY; RISK; FAT; QUANTIFICATION; DYSLIPIDEMIA; LIPOPROTEINS AB Background: The rise in LDL with egg feeding in lean insulin-sensitive (LIS) participants is 2- and 3-fold greater than in lean insulin-resistant (LIR) and obese insulin-resistant (OIR) participants, respectively. Objective: We determined whether differences in cholesterol absorption, synthesis, or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis. Design: Plasma sterols were measured by gas chromatography-mass spectrometry in a random subset of 34 LIS, 37 LIR, and 37 OIR participants defined by the insulin sensitivity index (SI) and by BMI criteria selected from a parent group of 197 participants. Cholestanol and plant sterols provide a measure of cholesterol absorption, and lathosterol provides a measure of cholesterol synthesis. Results: The mean (+/-SD) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 +/- 1.74 in LIS, 3.25 +/- 1.06 in LIR, and 2.82 +/- 1.08 in OIR participants. After adjustment for age and sex, the relations of the absorption sterol-cholesterol ratios were as follows: LIS. OIR (P < 0.001), LIS. LIR (P < 0.001), and LIR. OIR (P = 0.11). Lathosterol-cholesterol ratios were 0.71 +/- 0.32 in the LIS participants, 0.95 +/- 0.47 in the LIR participants, and 1.29 +/- 0.55 in the OIR participants. After adjustment for age and sex, the relations of lathosterol-cholesterol ratios were as follows: LIS, OIR (P < 0.001), LIS, LIR (P = 0.03), and LIR, OIR (P = 0.002). Total sterol concentrations were positively associated with SI and negatively associated with obesity, whereas lathosterol correlations were the opposite. Conclusions: Cholesterol absorption was highest in the LIS participants, whereas cholesterol synthesis was highest in the LIR and OIR participants. Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve SI and to decrease cholesterol overproduction in LIR and OIR persons. Am J Clin Nutr 2011;94:1182-8. C1 [Paramsothy, Pathmaja] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Paramsothy, Pathmaja; Knopp, Robert H.; Retzlaff, Barbara M.; Fish, Brian] Univ Washington, NW Lipid Res Clin, Seattle, WA 98195 USA. [Knopp, Robert H.; Kahn, Steven E.] Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Ma, Lina; Ostlund, Richard E., Jr.] Washington Univ, Sch Med, Div Endocrinol Metab & Lipid Res, St Louis, MO USA. RP Paramsothy, P (reprint author), 325 9th Ave,PSB 5064,UW Mailstop 359720, Seattle, WA 98104 USA. EM nmbob@uw.edu OI Kahn, Steven/0000-0001-7307-9002 FU Egg Nutrition Center; NIH [1KL2RR025015-01, RO1 50420, DK20579, RR00954]; Clinical Nutrition Research Unit at the University of Washington [DK 35816]; Diabetes and Endocrinology Research Center at the University of Washington [DK 17047]; General Clinical Research Center [RR 00037]; Department of Veterans Affairs FX Supported by a grant in aid from the Egg Nutrition Center (administered through the US Department of Agriculture), NIH 1KL2RR025015-01 (to PP); the Clinical Nutrition Research Unit at the University of Washington (DK 35816), the Diabetes and Endocrinology Research Center at the University of Washington (DK 17047), the General Clinical Research Center (RR 00037), the Department of Veterans Affairs (to SEK), and NIH grants RO1 50420, DK20579 and RR00954 (to REO). NR 38 TC 17 Z9 18 U1 0 U2 5 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2011 VL 94 IS 5 BP 1182 EP 1188 DI 10.3945/ajcn.110.006668 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 837VV UT WOS:000296236100005 PM 21940599 ER PT J AU Kurtz, B Thibault, HB Raher, MJ Popovich, JR Cawley, S Atochin, DN Hayton, S Shakartzi, HR Huang, PL Bloch, KD Buys, E Scherrer-Crosbie, M AF Kurtz, Baptiste Thibault, Helene B. Raher, Michael J. Popovich, John R. Cawley, Sharon Atochin, Dmitriy N. Hayton, Sarah Shakartzi, Hannah R. Huang, Paul L. Bloch, Kenneth D. Buys, Emmanuel Scherrer-Crosbie, Marielle TI Nitric oxide synthase 3 deficiency limits adverse ventricular remodeling after pressure overload in insulin resistance SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE oxidative stress; cardiac dysfunction ID HIGH-FAT DIET; CARDIAC-HYPERTROPHY; OXIDATIVE STRESS; HEART-FAILURE; MITOCHONDRIAL DYSFUNCTION; LIVER-MITOCHONDRIA; KNOCKOUT MICE; COMPLEX-III; HYPERTENSION; ACTIVATION AB Kurtz B, Thibault HB, Raher MJ, Popovich JR, Cawley S, Atochin DN, Hayton S, Shakartzi HR, Huang PL, Bloch KD, Buys E, Scherrer-Crosbie M. Nitric oxide synthase 3 deficiency limits adverse ventricular remodeling after pressure overload in insulin resistance. Am J Physiol Heart Circ Physiol 301: H2093-H2101, 2011. First published August 19, 2011; doi:10.1152/ajpheart.00744.2010.-Insulin resistance (IR) and systemic hypertension are independently associated with heart failure. We reported previously that nitric oxide synthase 3 (NOS3) has a beneficial effect on left ventricular (LV) remodeling and function after pressure-overload in mice. The aim of our study was to investigate the interaction of IR and NOS3 in pressure-overload-induced LV remodeling and dysfunction. Wild-type (WT) and NOS3-deficient (NOS3(-/-)) mice were fed either a standard diet (SD) or a high-fat diet (HFD) to induce IR. After 9 days of diet, mice underwent transverse aortic constriction (TAC). LV structure and function were assessed serially using echocardiography. Cardiomyocytes were isolated, and levels of oxidative stress were evaluated using 2',7'-dichlorodihydrofluorescein diacetate. Cardiac mitochondria were isolated, and mitochondrial respiration and ATP production were measured. TAC induced LV remodeling and dysfunction in all mice. The TAC-induced decrease in LV function was greater in SD-fed NOS3(-/-) mice than in SD-fed WT mice. In contrast, HFD-fed NOS3(-/-) developed less LV remodeling and dysfunction and had better survival than did HFD-fed WT mice. Seven days after TAC, oxidative stress levels were lower in cardiomyocytes from HFD-fed NOS3(-/-) than in those from HFD-fed WT. N(omega)-nitro-L-arginine methyl ester and mitochondrial inhibitors (rotenone and 2-thenoyltrifluoroacetone) decreased oxidative stress levels in cardiomyocytes from HFD-fed WT mice. Mitochondrial respiration was altered in NOS3(-/-) mice but did not worsen after HFD and TAC. In contrast with its protective role in SD, NOS3 increases LV adverse remodeling after pressure overload in HFD-fed, insulin resistant mice. Interactions between NOS3 and mitochondria may be responsible for increased oxidative stress levels in HFD-fed WT mice hearts. C1 [Kurtz, Baptiste; Thibault, Helene B.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Kurtz, Baptiste; Thibault, Helene B.; Raher, Michael J.; Popovich, John R.; Cawley, Sharon; Atochin, Dmitriy N.; Hayton, Sarah; Shakartzi, Hannah R.; Huang, Paul L.; Bloch, Kenneth D.; Buys, Emmanuel; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, Dept Med, Boston, MA 02114 USA. [Raher, Michael J.; Cawley, Sharon; Hayton, Sarah; Shakartzi, Hannah R.; Bloch, Kenneth D.; Buys, Emmanuel] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. EM marielle@crosbie.com RI Atochin, Dmitriy/Q-3150-2016 FU National Institutes of Health/National Heart, Lung, Blood Institute [1S10RR022586-01A1]; Federation Francaise de Cardiologie; Milton Fund FX This study was supported by a Shared Equipment Grant (National Institutes of Health/National Heart, Lung, Blood Institute 1S10RR022586-01A1; to M. Scherrer-Crosbie) as well as by fellowship grants from the Federation Francaise de Cardiologie (to B. Kurtz and H. B. Thibault) and by the Milton Fund (to M. Scherrer-Crosbie). NR 41 TC 2 Z9 2 U1 0 U2 4 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 NOV PY 2011 VL 301 IS 5 BP H2093 EP H2101 DI 10.1152/ajpheart.00744.2010 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 843ZN UT WOS:000296716900036 PM 21856905 ER PT J AU Shelton, RC McNeill, LH Puleo, E Wolin, KY Emmons, KM Bennett, GG AF Shelton, Rachel C. McNeill, Lorna H. Puleo, Elaine Wolin, Kathleen Y. Emmons, Karen M. Bennett, Gary G. TI The Association Between Social Factors and Physical Activity Among Low-Income Adults Living in Public Housing SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID UNITED-STATES; MINORITY WOMEN; CANCER PREVENTION; COLLEGE-STUDENTS; HEALTH BEHAVIOR; WORKING-CLASS; ENVIRONMENT; LEISURE; WALKING; OLDER AB Objectives. We sought to examine the association between structural, functional, and normative social factors and physical activity among urban, low-income, racially/ethnically diverse adults. Methods. We conducted a baseline cross-sectional survey among residents of 12 low-income housing communities in metropolitan Boston, Massachusetts. Participants were also asked to wear a pedometer for 5 days. We analyzed complete data from 1112 residents (weighted n = 1635). Results. Residents with smaller social networks were significantly less physically active than were residents with larger social networks (b = -1503.7; P = .01) and residents with conflicting demands were more active than were residents with none (b = 601.6; P = .01), when we controlled for employment status, gender, poverty level, current health status, age, and perceived safety. Social networks were most strongly associated with physical activity among Hispanics and younger residents (aged 18-35 years). Conclusions. These findings indicate that social factors, including social networks and role-related conflicting demands, may be important drivers of physical activity among low-income populations. Researchers and practitioners should consider social factors in developing multilevel physical activity interventions for this population. (Am J Public Health. 2011;101:2102-2110. doi: 10.2105/AJPH.2010.196030) C1 [Shelton, Rachel C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Sociomed Sci, New York, NY 10032 USA. [Shelton, Rachel C.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA. [McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Houston, TX 77030 USA. [Puleo, Elaine] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. [Wolin, Kathleen Y.] Washington Univ, Sch Med, St Louis, MO USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bennett, Gary G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. RP Shelton, RC (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Sociomed Sci, 722 W 168th St,Room 548, New York, NY 10032 USA. EM rshelton@post.harvard.edu RI Wolin, Kathleen/I-2154-2014 OI Wolin, Kathleen/0000-0001-7950-9042 FU National Cancer Institute [5R01CA098864-02, 1K22CA126992-01, K05 CA124415, 5R25-CA057711-14]; Liberty Mutual, National Grid, and the Patterson Fellowship; Mount Sinai Program in Cancer Prevention and Control: Multidisciplinary Training [5R25-CA081137] FX This research was supported by the National Cancer Institute (grants 5R01CA098864-02, 1K22CA126992-01, and K05 CA124415) and by support to the Dana-Farber Cancer Institute from Liberty Mutual, National Grid, and the Patterson Fellowship. Funding for the lead author was also provided through the National Cancer Institute by the Harvard Education Program in Cancer Prevention and Control (grant 5R25-CA057711-14) and the Mount Sinai Program in Cancer Prevention and Control: Multidisciplinary Training (grant 5R25-CA081137). NR 68 TC 22 Z9 22 U1 4 U2 25 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2011 VL 101 IS 11 BP 2102 EP 2110 DI 10.2105/AJPH.2010.196030 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 835NA UT WOS:000296041900022 PM 21330588 ER PT J AU Lund, BC Steinman, MA Chrischilles, EA Kaboli, PJ AF Lund, Brian C. Steinman, Michael A. Chrischilles, Elizabeth A. Kaboli, Peter J. TI Beers Criteria as a Proxy for Inappropriate Prescribing of Other Medications Among Older Adults SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE Beers criteria; health care; inappropriate drug use; older adult; quality indicators ID ADVERSE DRUG-REACTIONS; EXPLICIT CRITERIA; QUALITY; EVENTS; OUTPATIENTS; OUTCOMES; PEOPLE AB BACKGROUND: The Beers criteria are a compilation of medications deemed potentially inappropriate for older adults, widely used as a prescribing quality indicator. OBJECTIVE: To determine whether Beers criteria serve as a proxy measure for other forms of inappropriate prescribing, as measured by comprehensive implicit review. METHODS: Data for patients 65 years and older were obtained from the Veterans Affairs Enhanced Pharmacy Outpatient Clinic (EPOC) and the Iowa Medicaid Pharmaceutical Case Management (PCM) studies. Comprehensive measurement of prescribing quality was conducted using expert clinician review of medical records according to the Medication Appropriateness Index (MAI). MAI scores attributable to non-Beers medications were contrasted between patients who did and did not receive a Beers criteria medication. RESULTS: Beers criteria medications accounted for 12.9% (EPOC) and 14.0% (PCM) of total MAI scores. Importantly, non-Beers MAI scores were significantly higher in patients receiving a Beers criteria medication in both studies (EPOC: 15.1 vs 12.4, p = 0.02; PCM: 11.1 vs 8.7, p = 0.04), after adjusting for important confounding factors. CONCLUSIONS: Beers criteria utility extended beyond direct measurement of a limited set of inappropriate prescribing practices by serving as a clinically meaningful proxy for other inappropriate practices. Using prescribing quality indicators to guide interventions should thus identify patients for comprehensive medication review, rather than identifying specific medication targets for discontinuation. Future research should explore both the quality measurement and the intervention targeting applications of the Beers criteria, particularly when integrated with other indicators. C1 [Lund, Brian C.] Vet Affairs Iowa City Hlth Care Syst, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA USA. [Steinman, Michael A.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Steinman, Michael A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Chrischilles, Elizabeth A.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Kaboli, Peter J.] Univ Iowa, Dept Internal Med, Div Gen Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. RP Lund, BC (reprint author), Vet Affairs Iowa City Hlth Care Syst, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA USA. EM Brian.Lund@va.gov FU Health Services Research and Development Service, Department of Veterans Affairs [SAF98-152]; Research Career Development award [RCD 01-013-1]; Center for Research in the Implementation of Innovative Strategies in Practice at the Iowa City Veterans Affairs Medical Center [HFP 04-149]; State of Iowa General Assembly; Iowa Pharmacy Foundation, McKesson HBOC; Institute for the Advancement of Community Pharmacy; Agency for Healthcare Research and Quality (AHRQ) Centers for Education and Research on Therapeutics [5 U18 HS016094]; National Institute on Aging; American Federation for Aging Research [K23-AG030999] FX The Enhanced Pharmacy Outpatient Clinic trial was supported by the Health Services Research and Development Service, Department of Veterans Affairs, through an investigator-initiated research award (SAF98-152); Research Career Development award to Dr. Kaboli (RCD 01-013-1); and the Center for Research in the Implementation of Innovative Strategies in Practice (HFP 04-149) at the Iowa City Veterans Affairs Medical Center. The Iowa Medicaid Pharmaceutical Case Management program evaluation was funded by the State of Iowa General Assembly, the Iowa Pharmacy Foundation, McKesson HBOC, and the Institute for the Advancement of Community Pharmacy. This study was supported in part by an Agency for Healthcare Research and Quality (AHRQ) Centers for Education and Research on Therapeutics cooperative agreement #5 U18 HS016094. Dr. Steinman was supported by an award from the National Institute on Aging and the American Federation for Aging Research (K23-AG030999). NR 26 TC 19 Z9 23 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 EI 1542-6270 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD NOV PY 2011 VL 45 IS 11 BP 1363 EP 1370 DI 10.1345/aph.1Q361 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 845LK UT WOS:000296824000005 PM 21972251 ER PT J AU Niess, H Bao, Q Conrad, C Zischek, C Notohamiprodjo, M Schwab, F Schwarz, B Huss, R Jauch, KW Nelson, PJ Bruns, CJ AF Niess, Hanno Bao, Qi Conrad, Claudius Zischek, Christoph Notohamiprodjo, Mike Schwab, Felix Schwarz, Bettina Huss, Ralf Jauch, Karl-Walter Nelson, Peter J. Bruns, Christiane J. TI Selective Targeting of Genetically Engineered Mesenchymal Stem Cells to Tumor Stroma Microenvironments Using Tissue-Specific Suicide Gene Expression Suppresses Growth of Hepatocellular Carcinoma SO ANNALS OF SURGERY LA English DT Article ID BONE-MARROW; PERIPHERAL-BLOOD; BREAST-CARCINOMA; CANCER; METASTASIS; DELIVERY; ANGIOGENESIS; INVASION; THERAPY; PROLIFERATION AB Background: The use of engineered mesenchymal stem cells (MSCs) as therapeutic vehicles for the treatment of experimental pancreatic and breast cancer has been previously demonstrated. The potential application of MSCs for the treatment of hepatocellular carcinoma (HCC) has been controversial. The general approach uses engineered MSCs to target different aspects of tumor biology, including angiogenesis or the fibroblast-like stromal compartment, through the use of tissue-specific expression of therapeutic transgenes. The aim of the present study was (1) to evaluate the effect of exogenously added MSCs on the growth of HCC and (2) the establishment of an MSC-based suicide gene therapy for experimental HCC. Methods: Mesenchymal stem cells were isolated from bone marrow of C57/B16 p53(-/-) mice. The cells were injected into mice with HCC xenografts and the effect on tumor proliferation and angiogenesis was evaluated. The cells were then stably transfected with red fluorescent protein (RFP) or Herpes simplex virus thymidine kinase (HSV-Tk) gene under control of the Tie2 promoter/enhancer or the CCL5 promoter. Mesenchymal stem cells were injected intravenously into mice with orthotopically growing xenografts of HCC and treated with ganciclovir (GCV). Results: Ex vivo examination of hepatic tumors revealed tumor-specific recruitment, enhanced tumor growth, and increased microvessel density after nontherapeutic MSC injections. After their homing to the hepatic xenografts, engineered MSCs demonstrated activation of the Tie2 or CCL5 promoter as shown by RFP expression. Application of CCL5/HSV-TK transfected MSCs in combination with GCV significantly reduced tumor growth by 56.4% as compared with the control group and by 71.6% as compared with nontherapeutic MSC injections. CCL5/HSV-TK+ transfected MSCs proved more potent in tumor inhibition as compared with Tie2/HSV-TK+ MSCs. Conclusion: Exogenously added MSCs are recruited to growing HCC xenografts with concomitant activation of the CCL5 or Tie2 promoters within the MSCs. Stem cell-mediated introduction of suicide genes into the tumor followed by prodrug administration was effective for treatment of experimental HCC and thus may help fill the existing gap in bridging therapies for patients suffering from advanced HCCs. C1 [Niess, Hanno; Bao, Qi; Zischek, Christoph; Schwarz, Bettina; Jauch, Karl-Walter; Bruns, Christiane J.] Univ Munich, Dept Surg, D-81371 Munich, Germany. [Huss, Ralf] Univ Munich, Inst Pathol, D-8000 Munich, Germany. [Conrad, Claudius] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Conrad, Claudius] Harvard Stem Cell Inst, Boston, MA USA. [Schwab, Felix] Univ Hosp Munich, Josef Lissner Inst Biomed Imaging, Munich, Germany. [Notohamiprodjo, Mike] Univ Hosp Munich, Dept Clin Radiol, Munich, Germany. RP Bruns, CJ (reprint author), Univ Munich, Dept Surg, Marchioninistr 15, D-81371 Munich, Germany. EM Christiane.bruns@med.uni-muenchen.de FU Deutsche Forschungsgemeinschaft [SPP1190]; Wilhelm Sander-Stiftung; medical faculty of the University of Munich FX The work was supported by grants from the Deutsche Forschungsgemeinschaft (SPP1190 to CB and PJN), the Wilhelm Sander-Stiftung to PJN and the "Forderprogramm fur Forschung und Lehre" of the medical faculty of the University of Munich to HN. NR 44 TC 48 Z9 53 U1 0 U2 17 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 NOV PY 2011 VL 254 IS 5 BP 767 EP 775 DI 10.1097/SLA.0b013e3182368c4f PG 9 WC Surgery SC Surgery GA 844IK UT WOS:000296740700013 PM 22042469 ER PT J AU Jacoby, GA Griffin, CM Hooper, DC AF Jacoby, George A. Griffin, Caitlin M. Hooper, David C. TI Citrobacter spp. as a Source of qnrB Alleles SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MEDIATED QUINOLONE RESISTANCE; KLEBSIELLA-PNEUMONIAE; GENE; IDENTIFICATION; DETERMINANTS; PREVALENCE; EXPRESSION; WERKMANII; AMPC AB qnrB is the most common of the five qnr families and has the greatest number of allelic variants. Almost two-thirds of the qnrB alleles have been reported in Citrobacter spp., and several were shown to be located on the chromosome. In this study, PCR was used to investigate the prevalence of plasmid-mediated quinolone resistance genes in 71 clinical isolates belonging to the Citrobacter freundii complex. Thirty-seven percent contained qnrB alleles, including 7 (qnrB32 to qnrB38) that were novel and 1 pseudogene, while none contained qnrA, qnrC, qnrD, qnrS, or aac(6')-Ib-cr. When the strains were arrayed by related 16S rRNA sequence and further separated into subspecies by biochemical criteria, clustering of qnrB-positive strains was evident. In only two strains with qnrB2 and qnrB4 was quinolone resistance transferable by conjugation, and only these strains contained the ISCR1 sequence that is often associated with qnrB on plasmids. Five of 26 qnrB-positive strains contained integrase genes, but these included the strains with qnrB2 and qnrB4 as well as two strains with other transmissible plasmids. In a fully sequenced genome of Citrobacter youngae, a member of the C. freundii complex, another novel qnrB allele, qnrB39, occurs in a sequence of genes that is 90% identical to sequence surrounding integron-associated qnrB4 incorporated into plasmids. The chromosome of Citrobacter is the likely source of plasmid-mediated qnrB. C1 [Jacoby, George A.; Griffin, Caitlin M.] Lahey Clin Fdn, Burlington, MA 01805 USA. [Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Jacoby, GA (reprint author), Lahey Clin Fdn, 41 Mall Rd, Burlington, MA 01805 USA. EM george.a.jacoby@lahey.org FU National Institutes of Health, U.S. Public Health Service [R01 AI057576] FX This work was supported by grant R01 AI057576 (to D. C. H. and G.A.J.) from the National Institutes of Health, U.S. Public Health Service. NR 24 TC 43 Z9 44 U1 0 U2 10 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 NOV PY 2011 VL 55 IS 11 BP 4979 EP 4984 DI 10.1128/AAC.05187-11 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 839NX UT WOS:000296375600004 PM 21844311 ER PT J AU Hammond, SP Baden, LR Marty, FM AF Hammond, Sarah P. Baden, Lindsey R. Marty, Francisco M. TI Mortality in Hematologic Malignancy and Hematopoietic Stem Cell Transplant Patients with Mucormycosis, 2001 to 2009 SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MYCOSES STUDY-GROUP; EUROPEAN-ORGANIZATION; FUNGAL-INFECTIONS; SALVAGE THERAPY; ZYGOMYCOSIS; VORICONAZOLE; POSACONAZOLE; RECIPIENTS; DISEASES; OUTCOMES AB Mortality due to mucormycosis is high. We assessed clinical characteristics and mortality among stem cell transplant and hematologic malignancy patients diagnosed with mucormycosis from 2001 to 2009. Thirty patients were diagnosed with probable or proven mucormycosis during the study. Twenty-six were diagnosed premortem, and most were treated with liposomal amphotericin B single-agent antifungal therapy initially. While the initial antifungal and surgical treatment approach remained stable throughout the study period, 6-week mortality significantly declined over time (67% in 2001 to 2003 versus 45% in 2004 to 2006 versus 20% in 2007 to 2009 [P = 0.04]), as did 12-week mortality (78% in 2001 to 2003 versus 55% in 2004 to 2006 versus 20% in 2007 to 2009 [P = 0.01]). C1 [Hammond, Sarah P.] Brigham & Womens Hosp, Div Infect Dis, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hammond, SP (reprint author), Brigham & Womens Hosp, Div Infect Dis, Dana Farber Canc Inst, 75 Francis St,PBB A4, Boston, MA 02115 USA. EM shammond2@partners.org FU Scott James Thaler Award FX This work was supported in part by the Scott James Thaler Award. We declare no competing financial interests. NR 17 TC 16 Z9 16 U1 0 U2 2 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 NOV PY 2011 VL 55 IS 11 BP 5018 EP 5021 DI 10.1128/AAC.00536-11 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 839NX UT WOS:000296375600010 PM 21876046 ER PT J AU Robinson, EB Koenen, KC McCormick, MC Munir, K Hallett, V Happe, F Plomin, R Ronald, A AF Robinson, Elise B. Koenen, Karestan C. McCormick, Marie C. Munir, Kerim Hallett, Victoria Happe, Francesca Plomin, Robert Ronald, Angelica TI Evidence That Autistic Traits Show the Same Etiology in the General Population and at the Quantitative Extremes (5%, 2.5%, and 1%) SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MULTIPLE-REGRESSION ANALYSIS; RECIPROCAL SOCIAL-BEHAVIOR; CAST CHILDHOOD ASPERGER; TWIN DATA; INDIVIDUAL-DIFFERENCES; GENETIC-RELATIONSHIP; DISORDERS; SPECTRUM; HERITABILITY; CHILDREN AB Context: Genetic factors play an important role in the etiology of both autism spectrum disorders and autistic traits. However, little is known about the etiologic consistency of autistic traits across levels of severity. Objective: To compare the etiology of typical variation in autistic traits with extreme scoring groups (including top 1%) that mimicked the prevalence of diagnosed autism spectrum disorders in the largest twin study of autistic traits to date. Design: Twin study using phenotypic analysis and genetic model-fitting in the total sample and extreme scoring groups (top 5%, 2.5%, and 1%). Setting: A nationally representative twin sample from the general population of England. Participants: The families of 5968 pairs aged 12 years old in the Twins' Early Development Study. Main Outcome Measure: Autistic traits as assessed by the Childhood Autism Spectrum Test. Results: Moderate to high heritability was found for autistic traits in the general population (53% for females and 72% for males). High heritability was found in extreme-scoring groups. There were no differences in heritability among extreme groups or between the extreme groups and the general population. A continuous liability shift toward autistic trait affectedness was seen in the cotwins of individuals scoring in the top 1%, suggesting shared etiology between extreme scores and normal variation. Conclusion: This evidence of similar etiology across normal variation and the extremes has implications for molecular genetic models of autism spectrum disorders and for conceptualizing autism spectrum disorders as the quantitative extreme of a neurodevelopmental continuum. C1 [Robinson, Elise B.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Robinson, Elise B.; Koenen, Karestan C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Koenen, Karestan C.; McCormick, Marie C.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Robinson, Elise B.; Munir, Kerim] Harvard Univ, Sch Med, Childrens Hosp Boston, Mental Hlth & Dev Disabil Program,Div Dev Med, Boston, MA USA. [Munir, Kerim] Harvard Univ, Sch Med, Dept Psychiat, Childrens Hosp Boston, Boston, MA 02115 USA. [Koenen, Karestan C.] Harvard Univ, Harvard Ctr Dev Child, Cambridge, MA 02138 USA. [Hallett, Victoria; Happe, Francesca; Plomin, Robert; Ronald, Angelica] Kings Coll London, Inst Psychiat, Med Res Council Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. [Ronald, Angelica] Univ London, Dept Psychol Sci, Ctr Brain & Cognit Dev, London, England. RP Robinson, EB (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, 185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM erobinso@hsph.harvard.edu RI Happe, Francesca/D-5544-2012; Ronald, Angelica/C-7812-2009; Munir, Kerim/D-6910-2015; Koenen, Karestan/K-5402-2014; OI Ronald, Angelica/0000-0002-9576-2176; Munir, Kerim/0000-0002-2404-1806; McCormmick, Marie/0000-0002-3938-1707; Koenen, Karestan/0000-0003-3293-4281; Plomin, Robert/0000-0002-0756-3629 FU Medical Research Council [G0500079]; Harvard Medical School [MH71286]; Harvard School of Public Health [T32MH017119]; National Institute of Mental Health/National Institutes of Health at The Children's Hospital Boston FX The Twins Early Development Study is funded by grant G0500079 from the Medical Research Council. This study was supported by a National Institute of Mental Health/National Institutes of Health Research Fellowship at The Children's Hospital Boston, Harvard Medical School (grant MH71286) and the Training Program in Psychiatric Genetics and Translational Research at the Harvard School of Public Health (grant T32MH017119). NR 49 TC 93 Z9 95 U1 3 U2 23 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 NOV PY 2011 VL 68 IS 11 BP 1113 EP 1121 PG 9 WC Psychiatry SC Psychiatry GA 843CL UT WOS:000296649800006 PM 22065527 ER PT J AU Lewandrowski, K Gregory, K Macmillan, D AF Lewandrowski, Kent Gregory, Kimberly Macmillan, Donna TI Assuring Quality in Point-of-Care Testing Evolution of Technologies, Informatics, and Program Management SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID UNITED-STATES AB Context.-Managing the quality of point-of-care testing (POCT) is a continuing challenge. Advances in testing technologies and the development of specialized informatics for POCT have greatly improved the ability of hospitals to manage their POCT program. Objectives.-To present the evolving role of technology improvement, informatics, and program management as the key developments to ensure the quality of POCT. Data Sources.-This presentation is based on a review of the literature and on our experiences with POCT at the Massachusetts General Hospital (Boston). Conclusions.-Federal and state regulations, along with accreditation standards developed by the College of American Pathologists and The Joint Commission, have established guidelines for the performance of POCT and have provided a strong incentive to improve the quality of testing. Many instruments for POCT have incorporated advanced design features to prevent analytic and operator errors. This, along with the development of connectivity standards and specialized data management software, has enabled remote review of test data and electronic flow of information to hospital information systems. However, documentation of manually performed, visually read tests remains problematic and some POCT devices do not have adequate safeguards to prevent significant errors. In the past 2 decades the structure of a successful POCT management program has been defined, emphasizing the role of POCT managers working in conjunction with a pathology-based medical director. The critical skill set of POCT managers has also been identified. The POCT manager is now recognized as a true specialist in laboratory medicine. (Arch Pathol Lab Med. 2011;135:1405-1414; doi:10.5858/arpa.2011-0157-RA) C1 [Lewandrowski, Kent; Gregory, Kimberly; Macmillan, Donna] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lewandrowski, Kent] Harvard Univ, Sch Med, Boston, MA USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gray 5 Chem,55 Fruit St, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 13 TC 20 Z9 22 U1 1 U2 9 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 NOV PY 2011 VL 135 IS 11 BP 1405 EP 1414 DI 10.5858/arpa.2011-0157-RA PG 10 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 847KT UT WOS:000296972500009 PM 22032566 ER PT J AU Maurovich-Horvat, P Kallianos, K Engel, LC Szymonifka, J Fox, CS Hoffmann, U Truong, QA AF Maurovich-Horvat, Pal Kallianos, Kimberly Engel, Leif-Christopher Szymonifka, Jackie Fox, Caroline S. Hoffmann, Udo Truong, Quynh A. TI Influence of pericoronary adipose tissue on local coronary atherosclerosis as assessed by a novel MDCT volumetric method SO ATHEROSCLEROSIS LA English DT Article DE Coronary artery disease; Pericoronary fat; Epicardial fat; Adipose tissue; Inflammation; Computed tomography ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; VISCERAL ABDOMINAL FAT; PUBLIC-HEALTH PRACTICE; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; PERICARDIAL FAT; RISK-FACTORS; ASSOCIATION; ANGIOGRAPHY; INFLAMMATION AB Objective: Pericoronary adipose tissue (PCAT) may create a pro-inflammatory state, contributing to the development of coronary artery disease (CAD). We sought to evaluate the feasibility of a novel volumetric PCAT quantification method using a novel threshold based computed tomography approach. In addition we determined the relation between PCAT volumes and CAD. Methods: In 51 patients (49.5 +/- 5.1 years, 64.8% male) who underwent 64-slice MDCT, we measured threshold-based PCAT volumes using distance and anatomic-based methods. Using the most reproducible method, we performed the proximal 40-mm distance measurement in three groups as stratified by coronary plaque and high-sensitivity C-reactive protein (hs-CRP) levels: Group 1 (presence of coronary plaque, hs-CRP > 2.0 mg/L); an intermediate group (Group 2, no plaque, hs-CRP > 2.0 mg/L); and Group 3 (no plaque, hs-CRP < 1.0 mg/L). We compared PCAT volumes to the presence of coronary plaque on a patient (n = 51) and vessel (n = 153) basis. On a subsegment basis (n = 1224), we compared PCAT volume to the presence of plaque as well as plaque morphology. Results: Distance-based PCAT volume measurements yielded excellent reproducibility with intra-observer intraclass correlation (ICC) of 0.997 and inter-observer ICC of 0.951. On a both a per-patient and per-vessel analysis, adjusted PCAT volume was greater in patients with plaque (Group 1) than without plaque (Groups 2 and 3, p < 0.001). No difference in PCAT volume was seen between high and low hs-CRP groups without plaque (p = 0.51). Adjusted PCAT volumes were higher in subsegments with plaque as compared without (p < 0.001). Additionally, adjusted PCAT volume was greatest in subsegments with mixed plaque followed by non-calcified plaque, calcified plaque, and the lowest volume in segments with no plaque (p < 0.001). Conclusion: In this proof-of-concept study, threshold based PCAT volume assessment is feasible and highly reproducible. PCAT volume is increased in patients and vessels with coronary plaques. Surrounding vessel subsegments with coronary plaque, particularly mixed plaques, have greatest PCAT volume and highlight the effect of local PCAT in the development of coronary atherosclerosis. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Maurovich-Horvat, Pal; Kallianos, Kimberly; Engel, Leif-Christopher; Hoffmann, Udo; Truong, Quynh A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program,Div Cardiol, Boston, MA 02114 USA. [Maurovich-Horvat, Pal; Kallianos, Kimberly; Engel, Leif-Christopher; Hoffmann, Udo; Truong, Quynh A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Maurovich-Horvat, Pal] Semmelweis Univ, Ctr Heart, Budapest, Hungary. [Szymonifka, Jackie] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Truong, QA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program,Div Cardiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM qtruong@partners.org OI Maurovich-Horvat, Pal/0000-0003-0885-736X FU NIH [R01 HL080053, K23HL098370, L30HL093896]; Siemens Medical Solutions; General Electrics Healthcare; [TAMOP-4.2.2-08/01/KMR-2008-2004] FX Sources of funding: This work was supported by the NIH R01 HL080053, and in part supported by Siemens Medical Solutions and General Electrics Healthcare. Dr. Truong received support from NIH grant K23HL098370 and L30HL093896. Dr. Maurovich-Horvat received support from TAMOP-4.2.2-08/01/KMR-2008-2004. NR 23 TC 12 Z9 13 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 NOV PY 2011 VL 219 IS 1 BP 151 EP 157 DI 10.1016/j.atherosclerosis.2011.06.049 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 842HK UT WOS:000296587200023 PM 21782176 ER PT J AU Podar, K Zimmerhackl, A Fulciniti, M Tonon, G Hainz, U Tai, YT Vallet, S Halama, N Jager, D Olson, DL Sattler, M Chauhan, D Anderson, KC AF Podar, Klaus Zimmerhackl, Alexander Fulciniti, Mariateresa Tonon, Giovanni Hainz, Ursula Tai, Yu-Tzu Vallet, Sonia Halama, Niels Jaeger, Dirk Olson, Dian L. Sattler, Martin Chauhan, Dharminder Anderson, Kenneth C. TI The selective adhesion molecule inhibitor Natalizumab decreases multiple myeloma cell growth in the bone marrow microenvironment: therapeutic implications SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; integrin-alpha 4; bone marrow microenvironment; adhesion; cell adhesion-mediated drug resistance ID MEDIATED DRUG-RESISTANCE; STROMAL CELLS; IN-VIVO; ANGIOGENESIS; INTEGRIN; LINES; PROGRESSION; ACTIVATION; INTERLEUKIN-6; EXPRESSION AB Recent advances regarding the introduction of anti-adhesion strategies as a novel therapeutic concept in oncology hold great promise. Here we evaluated the therapeutic potential of the new-in-class-molecule selective-adhesion-molecule (SAM) inhibitor Natalizumab, a recombinant humanized IgG4 monoclonal antibody, which binds integrin-alpha 4, in multiple myeloma (MM). Natalizumab, but not a control antibody, inhibited adhesion of MM cells to non-cellular and cellular components of the microenvironment as well as disrupted the binding of already adherent MM cells. Consequently, Natalizumab blocked both the proliferative effect of MM-bone marrow (BM) stromal cell interaction on tumour cells, and vascular endothelial growth factor (VEGF)-induced angiogenesis in the BM milieu. Moreover, Natalizumab also blocked VEGF-and insulin-like growth factor 1 (IGF-1)-induced signalling sequelae triggering MM cell migration. In agreement with our in vitro results, Natalizumab inhibited tumour growth, VEGF secretion, and angiogenesis in a human severe combined immunodeficiency murine model of human MM in the human BM microenvironment. Importantly, Natalizumab not only blocked tumour cell adhesion, but also chemosensitized MM cells to bortezomib, in an in vitro therapeutically representative human MM-stroma cell co-culture system model. Our data therefore provide the rationale for the clinical evaluation of Natalizumab, preferably in combination with novel agents (e. g. bortezomib) to enhance MM cytotoxicity and improve patient outcome. C1 [Podar, Klaus] LeBow Inst Myeloma Therapeut, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Podar, Klaus; Halama, Niels; Jaeger, Dirk] Univ Heidelberg, Natl Ctr Tumour Dis NCT, Heidelberg, Germany. [Halama, Niels; Jaeger, Dirk] German Canc Res Ctr, Heidelberg, Germany. [Fulciniti, Mariateresa] VA Boston Healthcare Syst, Milan, Italy. [Tonon, Giovanni] Ist Sci San Raffaele, I-20132 Milan, Italy. [Vallet, Sonia] Massachusetts Gen Hosp, Ctr Multiple Myeloma, Boston, MA 02114 USA. [Vallet, Sonia] Harvard Univ, Sch Med, Boston, MA USA. [Olson, Dian L.] Mol Discovery Biogen Idec, Cambridge, MA USA. RP Podar, K (reprint author), LeBow Inst Myeloma Therapeut, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM klaus_podar@dfci.harvard.edu FU Multiple Myeloma Research Foundation (MMRF); Dunkin' Donuts Rising Star Award; National Institutes of Health [IP50 CA 100707, RO-1 CA 50947, PO-1 78378]; LeBow Fund; Biogen Idec; Elan; Millenium; Celgene; Novartis FX This work was supported by a Multiple Myeloma Research Foundation (MMRF) Senior Research Grant Award and the Dunkin' Donuts Rising Star Award (to K. P.); National Institutes of Health Grants IP50 CA 100707, RO-1 CA 50947 and PO-1 78378, as well as the LeBow Fund to Myeloma (to K. C. A.); K. P. received research support from Biogen Idec and Elan. K. C. Anderson is a consultant for and received research support from Millenium, Celgene and Novartis. D. L. O. is employee of Biogen Idec, Cambridge, MA. The other authors declare no potential conflicts of interest. NR 37 TC 27 Z9 29 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2011 VL 155 IS 4 BP 438 EP 448 DI 10.1111/j.1365-2141.2011.08864.x PG 11 WC Hematology SC Hematology GA 846LI UT WOS:000296901500006 PM 21923653 ER PT J AU Kong, CY Nattinger, KJ Hayeck, TJ Omer, ZB Wang, YC Spechler, SJ McMahon, PM Gazelle, GS Hur, C AF Kong, Chung Yin Nattinger, Kevin J. Hayeck, Tristan J. Omer, Zehra B. Wang, Y. Claire Spechler, Stuart J. McMahon, Pamela M. Gazelle, G. Scott Hur, Chin TI The Impact of Obesity on the Rise in Esophageal Adenocarcinoma Incidence: Estimates from a Disease Simulation Model SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; BODY-MASS INDEX; BARRETTS-ESOPHAGUS; GASTRIC CARDIA; ABDOMINAL OBESITY; UNITED-STATES; CLINICAL SPECTRUM; ACID REFLUX; POPULATION; PREVALENCE AB Background: The United States has experienced an alarming and unexplained increase in the incidence of esophageal adenocarcinoma (EAC) since the 1970s. A concurrent increase in obesity has led some to suggest a relationship between the two trends. We explore the extent of this relationship. Methods: Using a previously validated disease simulation model of white males in the United States, we estimated EAC incidence 1973 to 2005 given constant obesity prevalence and low population progression rates consistent with the early 1970s. Introducing only the observed, rising obesity prevalence, we calculated the incremental incidence caused by obesity. We compared these with EAC incidence data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry to determine obesity's contribution to the rise therein. Incidences were converted to absolute numbers of cases using U. S. population data. Results: Using constant obesity prevalence, we projected a total of 30,555 EAC cases cumulatively over 1973 to 2005 and 1,151 in 2005 alone. Incorporating the observed obesity trend resulted in 35,767 cumulative EACs and 1,608 in 2005. Estimates derived from SEER data showed 111,223 cumulative and 7,173 cases in 2005. We conclude that the rise in obesity accounted for 6.5% of the increase in EAC cases that occurred from 1973 to 2005 and 7.6% in the year 2005. Conclusion: Using published OR for EAC among obese individuals, we found that only a small percentage of the rise in EAC incidence is attributable to secular trends in obesity. Impact: Other factors, alone and in combination, should be explored as causes of the EAC epidemic. Cancer Epidemiol Biomarkers Prev; 20(11); 2450-6. (C) 2011 AACR. C1 [Kong, Chung Yin; Nattinger, Kevin J.; Hayeck, Tristan J.; McMahon, Pamela M.; Gazelle, G. Scott; Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Nattinger, Kevin J.; Hayeck, Tristan J.; Omer, Zehra B.; Hur, Chin] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Kong, Chung Yin; McMahon, Pamela M.; Gazelle, G. Scott; Hur, Chin] Harvard Univ, Sch Med, Boston, MA USA. [Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Wang, Y. Claire] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Spechler, Stuart J.] VA N Texas Hlth Care Syst, Dallas, TX USA. RP Hur, C (reprint author), 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM chur@mgh-ita.org OI Hur, Chin/0000-0002-2819-7576 FU AstraZeneca Pharmaceuticals; Ironwood Pharmaceuticals Inc.; Takeda Pharmaceutical Company Ltd.; XenoPort, Inc.; Torax Medical, Inc.; BARRX Medical, Inc.; GE Healthcare; National Cancer Institute at the NIH [U01CA152926, R01CA140574, K25CA133141, R00CA126147] FX S.Y. Spechler received grant/research support from AstraZeneca Pharmaceuticals and Ironwood Pharmaceuticals Inc.; consulting fee from Takeda Pharmaceutical Company Ltd.; grant/research support from XenoPort, Inc.; consulting fee from both Torax Medical and BARRX Medical, Inc. G. S. Gazelle received grant/research support and consulting fee from GE Healthcare.; This work was supported by the National Cancer Institute at the NIH (grant numbers U01CA152926 and R01CA140574 to C. Hur, K25CA133141 to C.Y. Kong, and R00CA126147 to P.M. McMahon). NR 61 TC 14 Z9 14 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 NOV PY 2011 VL 20 IS 11 BP 2450 EP 2456 DI 10.1158/1055-9965.EPI-11-0547 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 844RO UT WOS:000296765200014 PM 21930957 ER PT J AU Marshall, JR Tangen, CM Sakr, WA Wood, DP Berry, DL Klein, EA Lippman, SM Parnes, HL Alberts, DS Jarrard, DF Lee, WR Gaziano, JM Crawford, ED Ely, B Ray, M Davis, W Minasian, LM Thompson, IM AF Marshall, James R. Tangen, Catherine M. Sakr, Wael A. Wood, David P., Jr. Berry, Donna L. Klein, Eric A. Lippman, Scott M. Parnes, Howard L. Alberts, David S. Jarrard, David F. Lee, W. Robert Gaziano, J. Michael Crawford, E. David Ely, Benjamin Ray, Michael Davis, Warren Minasian, Lori M. Thompson, Ian M., Jr. TI Phase III Trial of Selenium to Prevent Prostate Cancer in Men with High-grade Prostatic Intraepithelial Neoplasia: SWOG S9917 SO CANCER PREVENTION RESEARCH LA English DT Article ID VITAMIN-E; SUBSEQUENT RISK; SERUM SELENIUM; CLINICAL-TRIAL; REPEAT BIOPSY; SELECT; SUPPLEMENTATION; CHEMOPREVENTION; ADENOCARCINOMA; ASSOCIATION AB The threat of prostate cancer and the significant and often negative impact of its treatment underscore the importance of prevention. High-grade prostatic intraepithelial neoplasia (HGPIN) has been identified as a potential premalignant lesion marking an increased risk of prostate cancer and substantial evidence suggests that men with HGPIN are in need of prostate cancer prevention. In vitro, in vivo, epidemiologic, and clinical trial evidence that selenium supplementation protects against prostate cancer motivated the study we report here: a double-blind, randomized, placebo-controlled trial of selenium 200 (mu g/d) as selenomethionine in men with HGPIN. The primary endpoint was progression of HGPIN to prostate cancer over a 3-year period. This National Cancer Institute Intergroup trial was coordinated by the Southwest Oncology Group (SWOG). Of 619 enrolled patients, 423 randomized men with HGPIN (212 selenium and 211 placebo) were eligible (by central pathology review) and included in the primary analysis. Three-year cancer rates were 36.6% (placebo) versus 35.6% (selenium; P = 0.73, adjusted). The majority of patients who developed cancer on trial (70.8%, selenium and 75.5%, placebo) had a Gleason score of 6 or less than 6; there were no differences in Gleason scores between the two arms. Subset analyses included the finding of a nonsignificantly reduced prostate cancer risk (relative risk = 0.82; 95% CI: 0.40-1.69) in selenium versus placebo patients in the lowest quartile of baseline plasma selenium level (<106 ng/mL). Overall, and in all other subsets defined by baseline blood selenium levels, selenium supplementation had no effect on prostate cancer risk. The 36% prostate cancer rate in men with HGPIN indicates the association of this lesion with an elevated prostate cancer risk. Future study in this setting should focus on selenium-deficient populations and selenium pharmacogenetics. Cancer Prev Res; 4(11); 1761-9. (C) 2011 AACR. C1 [Marshall, James R.] Roswell Pk Canc Inst, Dept Canc Prevent & Populat Sci, Buffalo, NY 14263 USA. [Tangen, Catherine M.; Ely, Benjamin] SW Oncol Grp Stat Ctr, Seattle, WA USA. [Sakr, Wael A.] Wayne State Univ, Detroit, MI USA. [Wood, David P., Jr.] Univ Michigan, Ann Arbor, MI 48109 USA. [Berry, Donna L.] Dana Farber Canc Inst, Boston, MA USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Canc & Leukemia Grp B, MAVERIC Cooperat Studies Program Coordinating Ctr, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Klein, Eric A.] Cleveland Clin, Cleveland, OH 44106 USA. [Lippman, Scott M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Parnes, Howard L.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Alberts, David S.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. [Jarrard, David F.] Univ Wisconsin, Madison, WI USA. [Lee, W. Robert] Duke Univ, Sch Med, Eastern Cooperat Oncol Grp, Durham, NC USA. [Crawford, E. David] Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. [Thompson, Ian M., Jr.] Univ Texas San Antonio, Hlth Sci Ctr, San Antonio, TX USA. RP Marshall, JR (reprint author), Roswell Pk Canc Inst, Dept Canc Prevent & Populat Sci, Elm & Carlton St, Buffalo, NY 14263 USA. EM james.marshall@roswellpark.org FU National Cancer Institute, DHHS [CA11083, CA35261, CA46282, CA35119, CA45377, CA35431, CA45450, CA27057, CA67663, CA128567, CA13612, CA74647, CA45807, CA58348, CA67575, CA63844, CA58882, CA46368, CA45560, CA63850, CA35262, CA16385, CA76132, CACA04919, CA76447, CA58416, CA46113, CA68183, CA2106, CA21115, CA59518] FX This investigation was supported in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA32102, CA38926, CA14028, CA35178, CA04919, CA35192, CA105409, CA86780, CA20319, CA95860, CA42777, CA58686, CA11083, CA35261, CA46282, CA35119, CA45377, CA35431, CA45450, CA27057, CA67663, CA128567, CA13612, CA74647, CA45807, CA58348, CA67575, CA63844, CA58882, CA46368, CA45560, CA63850, CA35262, CA16385, CA76132, CA68183, CACA04919, CA76447, CA58686, CA27057, CA58416, CA46113, CA68183, CA2106, CA21115, and CA59518. NR 52 TC 49 Z9 49 U1 0 U2 8 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 NOV PY 2011 VL 4 IS 11 BP 1761 EP 1769 DI 10.1158/1940-6207.CAPR-10-0343 PG 9 WC Oncology SC Oncology GA 844NA UT WOS:000296752800007 PM 21896650 ER PT J AU Lee, JE Baba, Y Ng, K Giovannucci, E Fuchs, CS Ogino, S Chan, AT AF Lee, Jung Eun Baba, Yoshifumi Ng, Kimmie Giovannucci, Edward Fuchs, Charles S. Ogino, Shuji Chan, Andrew T. TI Statin Use and Colorectal Cancer Risk According to Molecular Subtypes in Two Large Prospective Cohort Studies SO CANCER PREVENTION RESEARCH LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; POPULATION-BASED SAMPLE; MICROSATELLITE INSTABILITY; COLON-CANCER; PATHOLOGICAL EPIDEMIOLOGY; INDUCED APOPTOSIS; COMPETING RISKS; LOWERING DRUGS; BREAST-CANCER; ASPIRIN AB Use of statins is hypothesized to reduce colorectal cancer risk but the evidence remains inconsistent. This may be partly explained by differential associations according to tumor location or molecular subtypes of colorectal cancer. We examined the association between statin use and colorectal cancer risk according to tumor location, KRAS mutation status, microsatellite instability (MSI) status, PTGS2 (COX-2) expression, or CpG island methylator phenotype (CIMP) status in two large prospective cohort studies, the Nurses' Health Study and Health Professionals Follow-up Study. We applied Cox regression to a competing risks analysis. We identified 1,818 colorectal cancers during 1990 to 2006. Compared with nonusers, current statin use was not associated with colorectal cancer [relative risk (RR) = 0.99, 95% CI = 0.86-1.14] or colon cancer (RR = 1.10, 95% CI = 0.94-1.29) but was inversely associated with rectal cancer (RR = 0.59, 95% CI = 0.41-0.84, P(heterogeneity) < 0.001). When we examined the association within strata of KRAS mutation status, we found no association with KRAS-mutated cancers (RR = 1.20, 95% CI = 0.87-1.67) but did observe a possible inverse association among KRAS wild-type cancers (RR = 0.80, 95% CI = 0.60-1.06, P(heterogeneity) = 0.06). The association did not substantially differ by PTGS2 expression, MSI status, or CIMP status. Current statin use was not associated with risk of overall colorectal cancer. The possibility that statin use may be associated with lower risk of rectal cancer or KRAS wild-type colorectal cancer requires further confirmation. Cancer Prev Res; 4(11); 1808-15. (C) 2011 AACR. C1 [Lee, Jung Eun] Sookmyung Womens Univ, Dept Food & Nutr, Seoul, South Korea. [Baba, Yoshifumi; Ng, Kimmie; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Giovannucci, Edward; Fuchs, Charles S.; Chan, Andrew T.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji; Chan, Andrew T.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 728A, Boston, MA 02114 USA. EM achan@partners.org FU NIH/National Cancer Institute [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826, R01 CA151993, R01 CA137178] FX This work was supported by grants P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826, R01 CA151993, and R01 CA137178 from NIH/National Cancer Institute. NR 50 TC 27 Z9 28 U1 0 U2 2 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 NOV PY 2011 VL 4 IS 11 BP 1808 EP 1815 DI 10.1158/1940-6207.CAPR-11-0113 PG 8 WC Oncology SC Oncology GA 844NA UT WOS:000296752800012 PM 21680706 ER PT J AU Hanratty, R Chonchol, M Havranek, EP Powers, JD Dickinson, LM Ho, PM Magid, DJ Steiner, JF AF Hanratty, Rebecca Chonchol, Michel Havranek, Edward P. Powers, J. David Dickinson, L. Miriam Ho, P. Michael Magid, David J. Steiner, John F. TI Relationship between Blood Pressure and Incident Chronic Kidney Disease in Hypertensive Patients SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HEMODIALYSIS-PATIENTS; DIABETES-MELLITUS; RENAL-DISEASE; UNITED-STATES; PROGRESSION; POPULATION; PREVALENCE; DECLINE; TRIAL; TIME AB Background and objectives Hypertension is an important cause of chronic kidney disease (CKD). Identifying risk factors for progression to CKD in patients with normal kidney function and hypertension may help target therapies to slow or prevent decline of kidney function. Our objective was to identify risk factors for development of incident CKD and decline in estimated GFR (eGFR) in hypertensive patients. Design, setting, participants, & measurements Cox proportional hazards models were used to assess the relationship between incident CKD (defined as eGFR <60 ml/min per 1.73 m(2)) and potential risk factors for CKD from a registry of hypertensive patients. Results Of 43,305 patients meeting the inclusion criteria, 12.1% (5236 patients) developed incident CKD. Diabetes was the strongest predictor of incident CKD (hazard ratio, 1.96; 95% confidence interval, 1.84 to 2.09) and was associated with the greatest rate of decline in eGFR (-2.2 ml/min per 1.73 m(2) per year). Time-varying systolic BP was associated with incident CKD with risk increasing above 120 mmHg; each 10-mmHg increase in baseline and time-varying systolic BP was associated with a 6% increase in the risk of developing CKD (hazard ratio, 1.06; 95% confidence interval, 1.04 to 1.08 for both). Time-weighted systolic BP was associated with a more rapid decline in eGFR of an additional 0.2 ml/min per 1.73 m(2) per year decline for every 10-mmHg increase in systolic BP. Conclusions We found that time-varying systolic BP was associated with incident CKD, with an increase in risk above a systolic BP of 120 mmHg among individuals with hypertension. Clin J Am Soc Nephrol 6: 2605-2611, 2011. doi: 10.2215/CJN.02240311 C1 [Hanratty, Rebecca] Denver Hlth, Med Ctr, Denver, CO 80204 USA. [Chonchol, Michel] Univ Colorado, Div Renal Dis & Hypertens, Denver, CO 80202 USA. [Powers, J. David; Ho, P. Michael; Magid, David J.; Steiner, John F.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Dickinson, L. Miriam] Univ Colorado, Colorado Hlth Outcomes Program, Denver, CO USA. [Ho, P. Michael] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Hanratty, R (reprint author), Denver Hlth, Med Ctr, 777 Bannock St,MC 3600, Denver, CO 80204 USA. EM Rebecca.hanratty@dhha.org FU National Heart Lung and Blood Institute [U19 HL91179-01]; Veterans Affairs Health Services Research; Development Career Development Award [05-026] FX This study was conducted within the Cardiovascular Research Network, a consortium of research organizations affiliated with the HMO Research Network and sponsored by the National Heart Lung and Blood Institute (U19 HL91179-01). The results presented in this paper have not been published previously in whole or part, except in abstract form at the 43rd Annual American Society of Nephrology Conference.; Dr. Ho is supported by a Veterans Affairs Health Services Research and Development Career Development Award 05-026 and serves as a consultant for Wellpoint, Inc. NR 24 TC 14 Z9 16 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2011 VL 6 IS 11 BP 2605 EP 2611 DI 10.2215/CJN.02240311 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 845KJ UT WOS:000296821300010 PM 21921154 ER PT J AU Chan, KE Maddux, FW Tolkoff-Rubin, N Karumanchi, SA Thadhani, R Hakim, RM AF Chan, Kevin E. Maddux, Frank W. Tolkoff-Rubin, Nina Karumanchi, S. Ananth Thadhani, Ravi Hakim, Raymond M. TI Early Outcomes among Those Initiating Chronic Dialysis in the United States SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID RENAL-DISEASE PROGRAM; HEMODIALYSIS-PATIENTS; EARLY INTERVENTION; MORTALITY; HOSPITALIZATION; KIDNEY; RATES; DEATH AB Background and objectives Approximately one million Americans initiated chronic dialysis over the past decade; the first-year mortality rate reported by the U.S. Renal Data System was 19.6% in 2007. This estimate has historically excluded the first 90 days of chronic dialysis. Design, setting, participants, & measurements To characterize the mortality and hospitalization risks for patients starting chronic renal replacement therapy, we followed all patients initiating dialysis in 1733 facilities throughout the United States (n = 303,289). Mortality and hospitalizations within the first 90 days were compared with outcomes after this period, and the results were analyzed. Standard time-series analyses were used to depict the weekly risk estimates for each outcome. Results Between 1997 and 2009, >300,000 patients initiated chronic dialysis and were followed for >35 million dialysis treatments; the highest risk for morbidity and mortality occurred in the first 2 weeks of treatment. The initial 2-week risk of death for a typical dialysis patient was 2.72-fold higher, and the risk of hospitalization was 1.95-fold higher when compared to a patient who survived the first year of chronic dialysis (week 53 after initiation). Similarly, over the first 90 days, the risk of mortality and hospitalization remained elevated. Thereafter, between days 91 and 365, these risks decreased considerably by more than half. Surviving these first weeks of dialysis was most associated with the type of vascular access. Initiating dialysis with a fistula was associated with a decreased early death risk by 61%, whereas peritoneal dialysis decreased the risk by 87%. Conclusions The first 2 weeks of chronic dialysis are associated with heightened mortality and hospitalization risks, which remain elevated over the ensuing 90 days. Clin J Am Soc Nephrol 6: 2642-2649, 2011. doi: 10.2215/CJN.03680411 C1 [Chan, Kevin E.; Tolkoff-Rubin, Nina; Thadhani, Ravi] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Chan, Kevin E.; Maddux, Frank W.; Hakim, Raymond M.] Fresenius Med Care N Amer, Waltham, MA USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Div Nephrol, Bullfinch 127, Boston, MA 02114 USA. EM thadhani.r@mgh.harvard.edu FU Abbott Labs FX Drs. Chan, Hakim, and Maddux are employees of Fresenius Medial Care North America. Dr. Thadhani has received grants from Abbott Labs and is a consultant to Shire Biopharmaceuticals and Fresenius Medial Care North America. NR 31 TC 32 Z9 32 U1 0 U2 2 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 NOV PY 2011 VL 6 IS 11 BP 2642 EP 2649 DI 10.2215/CJN.03680411 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 845KJ UT WOS:000296821300015 PM 21959599 ER PT J AU Chan, KE Pflederer, TA Steele, DJR Lilly, MP Ikizler, TA Maddux, FW Hakim, RM AF Chan, Kevin E. Pflederer, Timothy A. Steele, David J. R. Lilly, Michael P. Ikizler, T. Alp Maddux, Frank W. Hakim, Raymond M. TI Access Survival amongst Hemodialysis Patients Referred for Preventive Angiography and Percutaneous Transluminal Angioplasty SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CLINICAL-TRIALS; BLOOD-FLOW; VITAMIN-D; SURVEILLANCE; SUBGROUPS; MORTALITY; STENOSIS; GRAFTS; RISK AB Background and objectives Referring hemodialysis patients for elective access angiography and percutaneous transluminal angioplasty (PTA) is commonly done to prevent access failure, yet the effectiveness of this procedure remains unclear. Design, setting, participants, & measures An observational matched cohort analysis among 40,132 Medicare beneficiaries receiving hemodialysis with a fistula or graft was performed. Cox regression was used to determine whether access intervention was associated with improved 1-year access survival. Results Nonsurgical access intervention was found to be frequent at a rate of 20.9 procedures per 100 access years. In the 1-year period after intervention using angiography and PTA, the overall access failure rate was 53.7 per 100 access years in the intervention group and 49.6 in the nonintervention group (HR = 1.02; 95% CI, 0.96 to 1.08). Similar findings were also seen when the analysis was repeated in only fistulas (HR = 1.06; 95% CI, 0.98 to 1.15) and grafts (HR = 0.95; 95% CI, 0.86 to 1.05). In patients with a low intra-access flow rate (HR = 0.86; 95% CI, 0.75 to 0.99) or a new access (HR = 0.79; 95% CI, 0.71 to 0.89), angiography and PTA significantly increased access survival when compared with nonintervention (P for interaction was <0.0001). Angiography-PTA-related upper-extremity hematoma, vessel injury, or embolism-thrombosis occurred in 1.1% of all patients. Conclusions Access characteristics significantly modify the survival benefits of angiography and PTA intervention where the benefits of these interventions are most seen in newer accesses or accesses with insufficient flow. Clin J Am Soc Nephrol 6: 2669-2680, 2011. doi: 10.2215/CJN.02860311 C1 [Chan, Kevin E.; Maddux, Frank W.; Hakim, Raymond M.] Fresenius Med Care N Amer, Div Clin Res, Waltham, MA 02451 USA. [Chan, Kevin E.; Steele, David J. R.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Pflederer, Timothy A.] Renal Care Associates, Morton, IL USA. [Lilly, Michael P.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Ikizler, T. Alp] Vanderbilt Univ, Div Nephrol, Nashville, TN USA. RP Chan, KE (reprint author), Fresenius Med Care N Amer, Div Clin Res, 920 Winter St, Waltham, MA 02451 USA. EM kevin.chan@fmc-na.com NR 28 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2011 VL 6 IS 11 BP 2669 EP 2680 DI 10.2215/CJN.02860311 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 845KJ UT WOS:000296821300019 PM 21959600 ER PT J AU Isakova, T Xie, HL Barchi-Chung, A Vargas, G Sowden, N Houston, J Wahl, P Lundquist, A Epstein, M Smith, K Contreras, G Ortega, L Lenz, O Briones, P Egbert, P Ikizler, TA Jueppner, H Wolf, M AF Isakova, Tamara Xie, Huiliang Barchi-Chung, Allison Vargas, Gabriela Sowden, Nicole Houston, Jessica Wahl, Patricia Lundquist, Andrew Epstein, Michael Smith, Kelsey Contreras, Gabriel Ortega, Luis Lenz, Oliver Briones, Patricia Egbert, Phyllis Ikizler, T. Alp Jueppner, Harald Wolf, Myles TI Fibroblast Growth Factor 23 in Patients Undergoing Peritoneal Dialysis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; MINERAL METABOLISM; HEMODIALYSIS-PATIENTS; PARATHYROID-HORMONE; MORTALITY RISK; PHOSPHATE; HYPERPHOSPHATEMIA; PROTEIN; VARIABILITY AB Background and objectives Fibroblast growth factor 23 (FGF23) is an independent risk factor for mortality in patients with ESRD. Before FGF23 testing can be integrated into clinical practice of ESRD, further understanding of its determinants is needed. Design, setting, participants, & measurements In a study of 67 adults undergoing peritoneal dialysis, we tested the hypothesis that longer dialysis vintage and lower residual renal function and renal phosphate clearance are associated with higher FGF23. We also compared the monthly variability of FGF23 versus parathyroid hormone (PTH) and serum phosphate. Results In unadjusted analyses, FGF23 correlated with serum phosphate (r = 0.66, P < 0.001), residual renal function (r = -0.37, P = 0.002), dialysis vintage (r = 0.31, P = 0.01), and renal phosphate clearance (r = -0.38, P = 0.008). In adjusted analyses, absence of residual renal function and greater dialysis vintage associated with higher FGF23, independent of demographics, laboratory values, peritoneal dialysis modality and adequacy, and treatment with vitamin D analogs and phosphate binders. Urinary and dialysate FGF23 clearances were minimal. In three serial monthly measurements, within-subject variability accounted for only 10% of total FGF23 variability compared with 50% for PTH and 60% for serum phosphate. Conclusions Increased serum phosphate, loss of residual renal function, longer dialysis vintage, and lower renal phosphate clearance are associated with elevated FGF23 levels in ESRD patients undergoing peritoneal dialysis. FGF23 may be a more stable marker of phosphate metabolism in ESRD than PTH or serum phosphate. Clin J Am Soc Nephrol 6: 2688-2695, 2011. doi: 10.2215/CJN.04290511 C1 [Isakova, Tamara; Xie, Huiliang; Barchi-Chung, Allison; Vargas, Gabriela; Sowden, Nicole; Houston, Jessica; Wahl, Patricia; Smith, Kelsey; Contreras, Gabriel; Ortega, Luis; Lenz, Oliver; Briones, Patricia; Wolf, Myles] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Miami, FL 33136 USA. [Lundquist, Andrew; Epstein, Michael] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Egbert, Phyllis; Ikizler, T. Alp] Vanderbilt Univ, Med Ctr, Div Nephrol, Nashville, TN USA. [Jueppner, Harald] Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. RP Wolf, M (reprint author), Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, 1120 NW 14th St, Miami, FL 33136 USA. EM mwolf2@med.miami.edu RI Lenz, Oliver/M-4672-2016 OI Lenz, Oliver/0000-0003-2997-3976 FU National Center for Research Resources [1UL-1RR024975]; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK 62849, K23DK087858, R01DK076116, R01DK081374]; Center for D-Receptor Activation Research FX This study was supported in part by the Clinical Translational Science Award 1UL-1RR024975 from the National Center for Research Resources (T.A.I.), and by grants K24 DK 62849 (T.A.I.), K23DK087858 (T.I.), R01DK076116 (M.W.), and R01DK081374 (M.W.) from the National Institute of Diabetes and Digestive and Kidney Diseases and the Center for D-Receptor Activation Research (T.A.I.). NR 34 TC 38 Z9 45 U1 0 U2 14 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 NOV PY 2011 VL 6 IS 11 BP 2688 EP 2695 DI 10.2215/CJN.04290511 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 845KJ UT WOS:000296821300021 PM 21903990 ER PT J AU Schutz, FAB Je, YJ Choueiri, TK AF Schutz, Fabio A. B. Je, Youjin Choueiri, Toni K. TI Hematologic toxicities in cancer patients treated with the multi-tyrosine kinase sorafenib: A meta-analysis of clinical trials SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE Vascular endothelial growth factor receptor; Targeted therapy; Tyrosine kinase inhibitors; Sorafenib; Anemia; Neutropenia; Lymphopenia; Thrombocytopenia; Bone marrow toxicities; Hematologic toxicities; Meta-analysis ID RENAL-CELL CARCINOMA; ACUTE MYELOID-LEUKEMIA; RANDOMIZED PHASE-II; GROWTH-FACTOR VEGF; STEM-CELLS; HEMATOPOIETIC-CELLS; FLT3 LIGAND; COMBINATION; BIAS; PROLIFERATION AB Background: Sorafenib is a vascular endothelial growth factor receptor tyrosine-kinase inhibitor currently used in several malignancies. While not a traditional cytotoxic chemotherapeutic agent, hematological toxicities have been reported with this drug but the incidence and risk have not been formerly assessed. We performed a meta-analysis to determine the incidence and risk of hematologic toxicities associated with sorafenib use. Methods: The databases of Medline were searched for articles from 1966 to May 2010. Abstracts presented at the American Society of Clinical Oncology meetings were also searched. Eligible studies include randomized trials with sorafenib, and adequate safety data profile reporting anemia, neutropenia, lymphopenia or thrombocytopenia. Statistical analyses were conducted to calculate the summary incidence, RR and 95% confidence intervals (CI). Results: A total of 3221 patients were included. The incidences of sorafenib-associated all-grade anemia, neutropenia, thrombocytopenia and lymphopenia were 43.9%, 18.0%, 25.3% and 34.1%, respectively. The incidences of high-grade events were 2.0%, 5.1%, 4.0% and 13.1%, respectively. Sorafenib was associated with a decreased risk of high-grade anemia (RR = 0.62; 95% CI, 0.39-0.98), an increased risk of all-grade (RR = 1.69; 95% CI, 1.33-2.17) and high-grade (RR = 1.61; 95% CI, 1.02-2.57) neutropenia, all-grade (RR = 2.56; 95% CI, 1.37-4.80) and high-grade (RR = 3.63; 95% CI, 1.98-6.66) thrombocytopenia, and high-grade lymphopenia (RR = 1.84; 95% CI, 1.22-2.78). Stratified analysis by the presence or not of concomitant chemotherapy demonstrated similar risks. Conclusions: Independent of cytotoxic chemotherapy, sorafenib has significant hematologic toxicities, with a decreased risk of anemia and increased risk of neutropenia, thrombocytopenia and lymphopenia. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Schutz, Fabio A. B.; Choueiri, Toni K.] Harvard Univ, Sch Med, Kidney Canc Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. [Je, Youjin] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Choueiri, TK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, 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 raw data and had the final responsibility for the decision to submit the manuscript for publication. NR 43 TC 30 Z9 30 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD NOV PY 2011 VL 80 IS 2 BP 291 EP 300 DI 10.1016/j.critrevonc.2010.11.007 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 843PA UT WOS:000296683200009 PM 21339073 ER PT J AU Habib, N Saedi, N Zachary, C AF Habib, Nancy Saedi, Nazanin Zachary, Christopher TI Cold-Induced Urticaria After Fractional Carbon Dioxide Laser Resurfacing of the Face SO DERMATOLOGIC SURGERY LA English DT Editorial Material C1 [Saedi, Nazanin; Zachary, Christopher] Univ Calif Irvine, Dept Dermatol, Irvine, CA 92717 USA. [Habib, Nancy] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Saedi, N (reprint author), Univ Calif Irvine, Dept Dermatol, Irvine, CA 92717 USA. EM nsaedi@gmail.com 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 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD NOV PY 2011 VL 37 IS 11 BP 1700 EP 1703 DI 10.1111/j.1524-4725.2011.02121.x PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 847KO UT WOS:000296972000023 PM 21883643 ER PT J AU Lee, CG Boyko, EJ Barrett-Connor, E Miljkovic, I Hoffman, AR Everson-Rose, SA Lewis, CE Cawthon, PM Strotmeyer, ES Orwoll, ES AF Lee, Christine G. Boyko, Edward J. Barrett-Connor, Elizabeth Miljkovic, Iva Hoffman, Andrew R. Everson-Rose, Susan A. Lewis, Cora E. Cawthon, Peggy Mannen Strotmeyer, Elsa S. Orwoll, Eric S. CA Osteoporotic Fractures Men MrOS TI Insulin Sensitizers May Attenuate Lean Mass Loss in Older Men With Diabetes SO DIABETES CARE LA English DT Article ID MUSCLE IN-VIVO; SKELETAL-MUSCLE; OSTEOPOROTIC FRACTURES; 1ST-DEGREE RELATIVES; METFORMIN INCREASES; BODY-COMPOSITION; EXERCISE; PROTEIN; PHOSPHORYLATION; TROGLITAZONE AB OBJECTIVE-To examine longitudinal changes in total and appendicular lean body mass in older men with impaired fasting glucose (IFG) or diabetes and to determine whether these changes differ by diabetes treatment. RESEARCH DESIGN AND METHODS-A total of 3,752 ambulatory men aged 65 years at baseline participated in a multicenter longitudinal cohort study. Baseline glycemic status was categorized as normoglycemia, IFG, undiagnosed/untreated diabetes, or treated diabetes. Insulin sensitizer medication use (metformin and/or thiazolidinediones) was assessed by prescription medication inventory. The change in total lean and appendicular lean mass was derived from dual X-ray absorptiometry scans taken at baseline and 3.5 +/- 0.7 years later. RESULTS-This male cohort included 1,853 individuals with normoglycemia, 1,403 with IFG, 234 with untreated diabetes, 151 with diabetes treated with insulin sensitizers, and 111 with diabetes treated without insulin sensitizers. Men with untreated diabetes, diabetes treated without insulin sensitizers, or IFG had greater percentage loss in total or appendicular lean mass (P <= 0.05 in comparison to normoglycemic men). There remained a significantly greater percentage loss in appendicular lean mass for these groups even after adjustment for medical comorbidities or lifestyle factors. In contrast, the percentage loss in total or appendicular lean mass in men with diabetes treated with insulin sensitizers was significantly less than that in normoglycemic men in minimally and fully adjusted models. CONCLUSIONS-Skeletal muscle loss was accelerated in men with IFG and diabetes, except when the latter was treated with insulin sensitizers. These findings suggest that insulin sensitizers may attenuate muscle loss C1 [Lee, Christine G.; Orwoll, Eric S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, La Jolla, CA 92093 USA. [Miljkovic, Iva; Strotmeyer, Elsa S.] Univ Pittsburgh, Pittsburgh, PA USA. [Hoffman, Andrew R.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Everson-Rose, Susan A.] Univ Minnesota, Minneapolis, MN USA. [Lewis, Cora E.] Univ Alabama, Birmingham, AL USA. [Cawthon, Peggy Mannen] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. RP Lee, CG (reprint author), Oregon Hlth & Sci Univ, Portland, OR 97201 USA. EM leechr@ohsu.edu RI Strotmeyer, Elsa/F-3015-2014; OI Orwoll, Eric/0000-0002-8520-7355; Miljkovic, Iva/0000-0002-3155-9777; Strotmeyer, Elsa/0000-0002-4093-6036 FU National Institutes of Health; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institute on Aging (NIA); National Center for Research Resources (NCRR); National Institutes of Health Roadmap for Medical Research [U01-AR45580, U01-AR45614, U01-AR45632, U01-AR45647, U01-AR45654, U01-AR45583, U01-AG18197, U01-AG027810, UL1-RR024140]; Building Interdisciplinary Careers in Women's Health Program [K12-HD043488-09]; American Diabetes Association [1-04-JF-46]; National Institute of Diabetes and Digestive and Kidney Diseases [K01-DK083029] FX The MrOS study was supported by funding from the National Institutes of Health. The following institutes provided support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and the National Institutes of Health Roadmap for Medical Research under the following grant numbers: U01-AR45580, U01-AR45614, U01-AR45632, U01-AR45647, U01-AR45654, U01-AR45583, U01-AG18197, U01-AG027810, and UL1-RR024140. C.G.L. received additional support from the Building Interdisciplinary Careers in Women's Health Program (grant number K12-HD043488-09). Additional support was provided by the American Diabetes Association (grant number 1-04-JF-46) to E.S.S. I.M. was supported by the Mentored Research Scientist Development Award from the National Institute of Diabetes and Digestive and Kidney Diseases (K01-DK083029). VA Puget Sound Health Care System provided support for participation of E.J.B. in this research. NR 22 TC 33 Z9 34 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2011 VL 34 IS 11 BP 2381 EP 2386 DI 10.2337/dc11-1032 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 847EQ UT WOS:000296955100010 PM 21926282 ER PT J AU Chang, MH Valdez, R Ned, RM Liu, TB Yang, QH Yesupriya, A Dowling, NF Meigs, JB Bowen, MS Khoury, MJ AF Chang, Man-huei Valdez, Rodolfo Ned, Renee M. Liu, Tiebin Yang, Quanhe Yesupriya, Ajay Dowling, Nicole F. Meigs, James B. Bowen, Michael S. Khoury, Muin J. TI Influence of Familial Risk on Diabetes Risk-Reducing Behaviors Among US Adults Without Diabetes SO DIABETES CARE LA English DT Article ID PUBLIC-HEALTH; IMPROVING HEALTH; PRIMARY-CARE; HISTORY; TOOL; POPULATION; PREVALENCE; MEDICINE; ADVICE AB OBJECTIVE-To test the association of family history of diabetes with the adoption of diabetes risk-reducing behaviors and whether this association is strengthened by physician advice or commonly known factors associated with diabetes risk. RESEARCH DESIGN AND METHODS-We used cross-sectional data from the 20052008 National Health and Nutrition Examination Survey (NHANES) to examine the effects of family history of diabetes on the adoption of selected risk-reducing behaviors in 8,598 adults (aged >= 20 years) without diabetes. We used multiple logistic regression to model three risk reduction behaviors (controlling or losing weight, increasing physical activity, and reducing the amount of dietary fat or calories) with family history of diabetes. RESULTS-Overall, 36.2% of U.S. adults without diabetes had a family history of diabetes. Among them, similar to 39.8% reported receiving advice from a physician during the past year regarding any of the three selected behaviors compared with 29.2% of participants with no family history (P < 0.01). In univariate analysis, adults with a family history of diabetes were more likely to perform these risk-reducing behaviors compared with adults without a family history. Physician advice was strongly associated with each of the behavioral changes (P < 0.01), and this did not differ by family history of diabetes. CONCLUSIONS-Familial risk for diabetes and physician advice both independently influence the adoption of diabetes risk-reducing behaviors. However, fewer than half of participants with familial risk reported receiving physician advice for adopting these behaviors. C1 [Chang, Man-huei; Valdez, Rodolfo; Ned, Renee M.; Liu, Tiebin; Yang, Quanhe; Yesupriya, Ajay; Dowling, Nicole F.; Bowen, Michael S.; Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chang, MH (reprint author), Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA. EM mdc9@cdc.gov FU Office of Public Health Genomics, CDC; National Institute of Diabetes and Digestive and Kidney Diseases [K24-DK-080140] FX Financial support for this work was provided by the Office of Public Health Genomics, CDC. J.B.M. was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (K24-DK-080140). NR 25 TC 12 Z9 12 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2011 VL 34 IS 11 BP 2393 EP 2399 DI 10.2337/dc11-0876 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 847EQ UT WOS:000296955100013 PM 21933907 ER PT J AU Sosenko, JM Skyler, JS Palmer, JP Krischer, JP Cuthbertson, D Yu, LP Schatz, DA Orban, T Eisenbarth, G AF Sosenko, Jay M. Skyler, Jay S. Palmer, Jerry P. Krischer, Jeffrey P. Cuthbertson, David Yu, Liping Schatz, Desmond A. Orban, Tihamer Eisenbarth, George CA Diabet Prevention Trial-Type 1 Type 1 Diabet TrialNet Study Grp TI A Longitudinal Study of GAD65 and ICA512 Autoantibodies During the Progression to Type 1 Diabetes in Diabetes Prevention Trial-Type 1 (DPT-1) Participants SO DIABETES CARE LA English DT Article ID INSULIN; MELLITUS; PREDICTION; ANTIBODIES; RISK AB OBJECTIVE-We examined changes in GAD65 and ICA-512 autoantibodies (GADA and IA-2A) during progression to type I diabetes (T1D). RESEARCH DESIGN AND METHODS-Diabetes Prevention Trial-Type 1 (OPT-1) participants were assessed for changes in positivity and titers of GADA and IA-2A during the progression to T1D. RESULTS-Among 99 progressors to T1D with GADA and IA-2A measurements at baseline and diagnosis (mean interval = 3.3 +/- 1.5 years), GADA positivity changed little and GADA titers decreased (P < 0.01). In contrast, both IA-2A positivity and titers increased substantially (P < 0.001). Even among those positive at baseline, IA-2A titers increased from baseline to diagnosis (n = 57; P < 0.001), whereas GADA titers decreased (n = 80; P < 0.01). The same patterns of change were also evident among those positive for both autoantibodies (n = 48) at baseline. CONCLUSIONS-IA-2A titers increase during the years before the diagnosis of T1D, even among those positive for IA-2A. In contrast, GADA titers tend to decline during those years. C1 [Sosenko, Jay M.; Skyler, Jay S.] Univ Miami, Div Endocrinol, Miami, FL USA. [Palmer, Jerry P.] Univ Washington, Div Endocrinol Metab & Nutr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Krischer, Jeffrey P.] Univ S Florida, Div Informat & Biostat, Tampa, FL USA. [Cuthbertson, David] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA. [Yu, Liping; Eisenbarth, George] Univ Colorado, HLA DNA Lab, Barbara Davis Ctr Childhood Diabet, Denver, CO 80202 USA. [Schatz, Desmond A.] Univ Florida, Div Endocrinol, Gainesville, FL USA. [Orban, Tihamer] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, Miami, FL USA. EM jsosenko@med.miami.edu RI Skyler, Jay/F-4211-2016 FU Type 1 Diabetes Trial Net Study Group; National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 DK061010, U01 DK061016, U01 DK061034, U01 DK061036, U01 DK061040, U01 DK061041, U01 DK061042, U01 DK061055, U01 DK061058, U01 DK084565, U01 DK085453, U01 DK085461, U01 DK085463, U01 DK085466, U01 DK085499, U01 DK085505, U01 DK085509, HHSN267200800019C]; National Center for Research Resources [UL1 RR024131, UL1 RR024139, UL1 RR024153, UL1 RR024975, UL1 RR024982, UL1 RR025744, UL1 RR025761, UL1 RR025780, UL1 RR029890, UL1 RR031986]; General Clinical Research Center Award [M01 RR00400]; Juvenile Diabetes Research Foundation International; American Diabetes Association FX The sponsor of the study was the Type 1 Diabetes Trial Net Study Group. Type 1 Diabetes Trial Net Study Group is a clinical trials network funded by the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, through the cooperative agreements U01 DK061010, U01 DK061016, U01 DK061034, U01 DK061036, U01 DK061040, U01 DK061041, U01 DK061042, U01 DK061055, U01 DK061058, U01 DK084565, U01 DK085453, U01 DK085461, U01 DK085463, U01 DK085466, U01 DK085499, U01 DK085505, U01 DK085509, and a contract HHSN267200800019C; the National Center for Research Resources, through Clinical Translational Science Awards UL1 RR024131, UL1 RR024139, UL1 RR024153, UL1 RR024975, UL1 RR024982, UL1 RR025744, UL1. RR025761, UL1 RR025780, UL1 RR029890, UL1 RR031986, and General Clinical Research Center Award M01 RR00400; the Juvenile Diabetes Research Foundation International; and the American Diabetes Association. NR 11 TC 13 Z9 14 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2011 VL 34 IS 11 BP 2435 EP 2437 DI 10.2337/dc11-0981 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 847EQ UT WOS:000296955100022 PM 21911777 ER PT J AU Peters, A Laffel, L AF Peters, Anne Laffel, Lori CA Amer Diabet Assoc Transitions TI Diabetes Care for Emerging Adults: Recommendations for Transition From Pediatric to Adult Diabetes Care Systems SO DIABETES CARE LA English DT Editorial Material ID AMERICAN YOUTH PREVALENCE; DISEASE RISK-FACTORS; QUALITY-OF-LIFE; YOUNG-ADULTS; GLYCEMIC CONTROL; CLINICAL CHARACTERISTICS; DEPRESSIVE SYMPTOMS; INTENSIVE TREATMENT; ADOLESCENT FEMALES; EATING HABITS C1 [Laffel, Lori] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Peters, Anne] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. RP Laffel, L (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM lori.laffel@joslin.harvard.edu OI Peters, Anne/0000-0003-0520-0776 FU NIDDK NIH HHS [R01 DK095273] NR 78 TC 133 Z9 135 U1 12 U2 29 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 NOV PY 2011 VL 34 IS 11 BP 2477 EP 2485 DI 10.2337/dc11-1723 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 847EQ UT WOS:000296955100031 PM 22025785 ER PT J AU Ritholz, MD Beverly, EA Abrahamson, MJ Brooks, KM Hultgren, BA Weinger, K AF Ritholz, Marilyn D. Beverly, Elizabeth A. Abrahamson, Martin J. Brooks, Kelly M. Hultgren, Brittney A. Weinger, Katie TI Physicians' Perceptions of the Type 2 Diabetes Multidisciplinary Treatment Team A Qualitative Study SO DIABETES EDUCATOR LA English DT Article ID PRIMARY-CARE; MANAGEMENT; COMPLICATIONS; INSULIN; PART AB Purpose The purpose of this study was to explore physicians' perceptions of the multidisciplinary type 2 diabetes treatment team. Methods Nineteen physicians (74% endocrinologists; 26% primary care) participated in semistructured interviews. Audiorecorded data were transcribed, coded, and analyzed using thematic analysis and NVivo 8 software. Results Physicians considered the multidisciplinary team, including a physician and diabetes educator, as very important to diabetes treatment. Participants described how diabetes, with its many comorbidities and challenging lifestyle recommendations, is difficult for any single physician to treat. They further described how the team's diverse staff offers complementary skills and more contact time for assessment and treatment of patients, developing treatment relationships, and supporting patients in learning diabetes self-care. Physicians stressed the necessity of regular and ongoing communication among team members to ensure patients receive consistent information, and some reported that institutional factors interfere with intra-team communication. They also expressed concerns about the team approach in relation to individualized treatment and patients' reluctance to see multiple providers. Conclusions This study highlights physicians' positive perceptions of and concerns about the type 2 diabetes multidisciplinary team. Further study of diabetes educators' and patients' perceptions of the team approach is needed. C1 [Ritholz, Marilyn D.; Beverly, Elizabeth A.; Abrahamson, Martin J.; Brooks, Kelly M.; Hultgren, Brittney A.; Weinger, Katie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ritholz, Marilyn D.; Beverly, Elizabeth A.; 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, 1 Joslin Pl, Boston, MA 02215 USA. EM Katie.Weinger@joslin.harvard.edu FU Kathleen P. Welsh Fund; NIDDK [RO1-060115]; Diabetes and Endocrinology Research Core NIH [P30 DK36836]; NIH [T32 DK007260] FX The authors thank the physicians who shared their experiences and perceptions with us. This study was supported by grants from the Kathleen P. Welsh Fund, NIDDK RO1-060115, the Diabetes and Endocrinology Research Core NIH P30 DK36836, and the NIH Training Grant No. T32 DK007260. NR 33 TC 6 Z9 6 U1 0 U2 7 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 NOV-DEC PY 2011 VL 37 IS 6 BP 794 EP 800 DI 10.1177/0145721711423320 PG 7 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 845XZ UT WOS:000296862200006 PM 22002972 ER PT J AU Zorick, T Sugar, CA Hellemann, G Shoptaw, S London, ED AF Zorick, Todd Sugar, Catherine A. Hellemann, Gerhard Shoptaw, Steve London, Edythe D. TI Poor response to sertraline in methamphetamine dependence is associated with sustained craving for methamphetamine SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Antidepressants; Sertraline; Methamphetamine; Addiction; Craving; Classification and regression trees ID PLACEBO-CONTROLLED TRIAL; DRUG-USERS; DEPRESSION; WITHDRAWAL; SEVERITY; PHARMACOTHERAPY; FLUOXETINE; MANAGEMENT; INVENTORY; OUTCOMES AB Background: Depression is common among individuals with methamphetamine (MA) use disorders. As agents that enhance serotonergic function are frequently used to treat depression, one might predict that they would be useful medications for MA dependence. However, clinical trials of serotonergic agents for MA addiction have been unsuccessful. Objective: To identify factors that distinguish MA-dependent research participants who increased MA self-administration while receiving treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline from other groups of participants. Method: Using a dataset from a 12-week randomized, placebo-controlled trial of sertraline (100 mg daily) for MA addiction, we identified participants who had completed at least 8 weeks of the trial (n = 61 sertraline, n = 68 placebo). We compared the proportions of MA-positive urine tests for weeks 8-12 of the trial for these subjects to their pre-randomization baseline, and identified those subjects who increased MA use during treatment. Using classification trees, we then assessed all data collected during the study to identify factors associated with increasing MA use during treatment with sertraline, compared to placebo. Results: More subjects in the sertraline condition increased MA use during treatment (n = 13) than in the placebo condition (n = 5: p = 0.03). Classification trees identified multiple factors from both pre-treatment and in-treatment data that were associated with increased MA use during treatment. Only elevated in-treatment craving for MA specifically characterized subjects in the sertraline group who increased their MA use. Conclusions: Some MA-abusing individuals treated with SSRIs have sustained craving with an increased propensity to relapse during treatment despite psychosocial treatment interventions. Published by Elsevier Ireland Ltd. C1 [Zorick, Todd] Greater Los Angeles Vet Adm Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA. [Zorick, Todd; Sugar, Catherine A.; Hellemann, Gerhard; London, Edythe D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. [Shoptaw, Steve] Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA 90095 USA. [London, Edythe D.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [London, Edythe D.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. RP Zorick, T (reprint author), 11301 Wilshire Blvd,MC 116A, Los Angeles, CA 90073 USA. EM todd.zorick@va.gov FU NIH [R01 DA010923, P50 DA018185, P20 DA022539] FX NIH Grants R01 DA010923 (SS), P50 DA018185 (SS, EDL), P20 DA022539 (EDL), endowments from the Katherine K. and Thomas P. Pike Chair in Addiction Studies (EDL), and the Marjorie M. Greene Trust. NR 34 TC 7 Z9 7 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD NOV 1 PY 2011 VL 118 IS 2-3 BP 500 EP 503 DI 10.1016/j.drugalcdep.2011.04.015 PG 4 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 837EL UT WOS:000296173800060 PM 21592681 ER PT J AU Johnson, JR Menard, ME Lauderdale, TL Kosmidis, C Gordon, D Collignon, P Maslow, JN Andrasevic, AT Kuskowski, MA AF Johnson, James R. Menard, Megan E. Lauderdale, Tsai-Ling Kosmidis, Chris Gordon, David Collignon, Peter Maslow, Joel N. Andrasevic, Arjana Tambic Kuskowski, Michael A. CA Trans-Global Initiative TI Global Distribution and Epidemiologic Associations of Escherichia coli Clonal Group A, 1998-2007 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID URINARY-TRACT-INFECTIONS; TRIMETHOPRIM-SULFAMETHOXAZOLE RESISTANCE; EXTRAINTESTINAL INFECTIONS; UNCOMPLICATED CYSTITIS; MOLECULAR EPIDEMIOLOGY; NEONATAL MENINGITIS; COMMUNITY; PYELONEPHRITIS; O-18-K1-H7; PREVALENCE AB Escherichia coli clonal group A (CGA) was first reported in 2001 as an emerging multidrug-resistant extraintestinal pathogen. Because CGA has considerable implications for public health, we examined the trends of its global distribution, clinical associations, and temporal prevalence for the years 1998-2007. We characterized 2,210 E. coli extraintestinal clinical isolates from 32 centers on 6 continents by CGA status for comparison with trimethoprim/sulfamethoxazole (TMP/SMZ) phenotype, specimen type, inpatient/outpatient source, and adult/child host; we adjusted for clustering by center. CGA prevalence varied greatly by center and continent, was strongly associated with TMP/SMZ resistance but not with other epidemiologic variables, and exhibited no temporal prevalence trend. Our findings indicate that CGA is a prominent, primarily TMP/SMZ-resistant extraintestinal pathogen concentrated within the Western world, with considerable pathogenic versatility. The stable prevalence of CGA over time suggests full emergence by the late 1990s, followed by variable endemicity worldwide as an antimicrobial drug resistant public health threat. C1 [Johnson, James R.; Menard, Megan E.; Kuskowski, Michael A.] VA Med Ctr, Minneapolis, MN 55417 USA. [Johnson, James R.] Univ Minnesota, Infect Dis Fellowship Program, Minneapolis, MN USA. [Lauderdale, Tsai-Ling] Natl Hlth Res Inst, Zhunan, Taiwan. [Kosmidis, Chris] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Gordon, David; Collignon, Peter] Australian Natl Univ, Canberra, ACT, Australia. [Collignon, Peter] Canberra Hosp, Canberra, ACT, Australia. [Maslow, Joel N.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Maslow, Joel N.] Univ Penn, Philadelphia, PA 19104 USA. [Andrasevic, Arjana Tambic] Univ Hosp Infect Dis, Zagreb, Croatia. RP Johnson, JR (reprint author), VA Med Ctr, 1 Vet Dr, Minneapolis, MN 55417 USA. EM johns007@umn.edu RI Lauderdale, Tsai-Ling/B-2660-2010; Toniolo, Antonio/B-4103-2015; OI Toniolo, Antonio/0000-0003-3008-2126; Kosmidis, Chris/0000-0003-0662-1265 FU Office of Research and Development, Medical Research Service, US Department of Veterans Affairs; Merck, Inc.; Rochester Medical Group FX This material is based on work supported by Office of Research and Development, Medical Research Service, US Department of Veterans Affairs (J.R.J.). J.R.J. has received research support (grant and contract) from Merck, Inc., and Rochester Medical Group. NR 25 TC 19 Z9 19 U1 1 U2 8 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2011 VL 17 IS 11 BP 2001 EP 2009 DI 10.3201/eid1711.110488 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 843KI UT WOS:000296670300002 PM 22099087 ER PT J AU Ryan, ET AF Ryan, Edward T. TI Haiti in the Context of the Current Global Cholera Pandemic SO EMERGING INFECTIOUS DISEASES LA English DT Editorial Material C1 [Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Ryan, Edward T.] Harvard Univ, Sch Med, Boston, MA USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM etryan@partners.org NR 0 TC 5 Z9 5 U1 0 U2 2 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2011 VL 17 IS 11 BP 2175 EP 2176 DI 10.3201/eid1711.110849 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 843KI UT WOS:000296670300045 PM 22204041 ER PT J AU Konstas, AA Digumarthy, SR Avery, LL Wallace, KL Lisovsky, M Misdraji, J Hahn, PF AF Konstas, Angelos A. Digumarthy, Subba R. Avery, Laura L. Wallace, Karen L. Lisovsky, Mikhail Misdraji, Joseph Hahn, Peter F. TI Congenital portosystemic shunts: Imaging findings and clinical presentations in 11 patients SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Congenital posrtosystemic shunts; Abernethy malformation; Park classification; Splenic artery aneurysms ID SPLENIC ARTERY ANEURYSM; VENOUS SHUNT; PORTAL-VEIN; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; HEPATOPULMONARY SYNDROME; LIVER-CIRRHOSIS; ABERNETHY MALFORMATION; PULMONARY-HYPERTENSION; SPLENORENAL SHUNT; PORTACAVAL-SHUNT AB Objective: To evaluate the clinical anatomy and presentations of congenital portosystemic shunts, and determine features that promote recognition on imaging. Materials and methods: Institutional review board approval was obtained for this HIPAA-compliant study. The requirement for written informed consent was waived. Radiology reports were retrospectively reviewed from non-cirrhotic patients who underwent imaging studies from January 1999 through February 2009. Clinical sources reviewed included electronic medical records, archived images and histopathological material. Results: Eleven patients with congenital portosystemic shunts were identified (six male and five female; age range 20 days to 84 years). Seven patients had extrahepatic and four patients had intrahepatic shunts. All 11 patients had absent or hypoplastic intrahepatic portal veins, a feature detected by CT and MRI, but not by US. Seven patients presented with shunt complications and four with presentations unrelated to shunt pathophysiology. Three adult patients had four splenic artery aneurysms. Prospective radiological evaluation of five adult patients with cross-sectional imaging had failed prospectively to recognize the presence of congenital portosystemic shunts on one or more imaging examinations. Conclusions: Congenital portosystemic shunts are associated with splenic artery aneurysms, a previously unrecognized association. Portosystemic shunts were undetected during prospective radiologic evaluation in the majority of adult patients, highlighting the need to alert radiologists to this congenital anomaly. (C) 2010 Published by Elsevier Ireland Ltd. C1 [Konstas, Angelos A.; Digumarthy, Subba R.; Avery, Laura L.; Hahn, Peter F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Konstas, Angelos A.; Digumarthy, Subba R.; Avery, Laura L.; Lisovsky, Mikhail; Misdraji, Joseph; Hahn, Peter F.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wallace, Karen L.] Mt Auburn Hosp, Dept Radiol, Cambridge, MA 02138 USA. [Wallace, Karen L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Lisovsky, Mikhail; Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Konstas, AA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 210, Boston, MA 02114 USA. EM akonstas@partners.org NR 34 TC 16 Z9 18 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD NOV PY 2011 VL 80 IS 2 BP 175 EP 181 DI 10.1016/j.ejrad.2009.12.031 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 839JC UT WOS:000296360500033 PM 20106622 ER PT J AU Roemer, FW Kwoh, CK Hannon, MJ Crema, MD Moore, CE Jakicic, JM Green, SM Guermazi, A AF Roemer, Frank W. Kwoh, C. Kent Hannon, Michael J. Crema, Michel D. Moore, Carolyn E. Jakicic, John M. Green, Stephanie M. Guermazi, Ali TI Semiquantitative assessment of focal cartilage damage at 3 T MRI: A comparative study of dual echo at steady state (DESS) and intermediate-weighted (IW) fat suppressed fast spin echo sequences SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE MRI; Cartilage; Knee; Focal defect; Osteoarthritis ID ARTICULAR-CARTILAGE; WATER-EXCITATION; NATURAL-HISTORY; KNEE; DEFECTS; OSTEOARTHRITIS; PATHOLOGY; PROTOCOL; 3-TESLA; LESIONS AB Purpose: The aim of the study was to compare semiquantitative assessment of focal cartilage damage using the dual echo at steady state (DESS)- and intermediate-weighted (IW) fat suppressed (fs) sequences at 3 T MRI. Methods: Included were 201 subjects aged 35-65 with frequent knee pain. MRI was performed with the same sequence protocol as in the Osteoarthritis Initiative (OAI): sagittal IW fs, triplanar DESS and coronal IW sequences. Cartilage status was scored according to the WORMS system using all five sequences. A total of 243 focal defects were detected. In an additional consensus reading, the lesions were evaluated side-by-side using only the sagittal DESS and IW fs sequences. Lesion conspicuity was graded from 0 to 3, intrachondral signal changes adjacent to the defect were recorded and the sequence that depicted the lesion with larger diameter was noted. Wilcoxon signed-rank tests, controlled for clustering by person, were used to examine differences between the sequences. Results: 37 (17.5%) of the scorable lesions were located in the medial tibio-femoral (TF), 48 (22.7%) in the lateral TF and 126 (59.7%) in the patello-femoral compartment. 82.5% were superficial and 17.5% full-thickness defects. Conspicuity was superior for the IW sequence (p < 0.001). The DESS sequence showed moreassociated intrachondral signal changes (p < 0.001). In 103 (48.8%) cases, the IW fs sequence depicted the lesions as being larger (p < 0.001). Conclusions: The IW fs sequence detected more and larger focal cartilage defects than the DESS. More intrachondral signal changes were observed with the DESS. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Roemer, Frank W.; Crema, Michel D.; Guermazi, Ali] Boston Univ, Dept Radiol, Med Ctr, Quantitat Imaging Ctr, Boston, MA 02118 USA. [Roemer, Frank W.] Klinikum Augsburg, Dept Radiol, Augsburg, Germany. [Kwoh, C. Kent; Hannon, Michael J.; Green, Stephanie M.] Univ Pittsburgh, Div Rheumatol & Clin Immunol, Sch Med, Pittsburgh, PA 15260 USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Moore, Carolyn E.] Texas Womans Univ, Dept Nutr & Food Sci, Denton, TX 76204 USA. [Jakicic, John M.] Univ Pittsburgh, Dept Hlth & Phys Act, Pittsburgh, PA 15260 USA. RP Roemer, FW (reprint author), Boston Univ, Dept Radiol, Med Ctr, Quantitat Imaging Ctr, FGH Bldg,3rd Floor,820 Harrison Ave, Boston, MA 02118 USA. EM froemer@bu.edu FU Beverage Institute for Health Wellness FX The JOG study is funded by a grant from the Beverage Institute for Health & Wellness. NR 20 TC 32 Z9 32 U1 3 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD NOV PY 2011 VL 80 IS 2 BP E126 EP E131 DI 10.1016/j.ejrad.2010.07.025 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 839JC UT WOS:000296360500020 PM 20833493 ER PT J AU Lin, XY Cai, TX Wu, MC Zhou, Q Liu, G Christiani, DC Lin, XH AF Lin, Xinyi Cai, Tianxi Wu, Michael C. Zhou, Qian Liu, Geoffrey Christiani, David C. Lin, Xihong TI Kernel Machine SNP-Set Analysis for Censored Survival Outcomes in Genome-Wide Association Studies SO GENETIC EPIDEMIOLOGY LA English DT Article DE Cox model; genetic studies; gene-based analysis; kernel machine; multi-locus test; score test; single nucleotide polymorphism ID LINKAGE DISEQUILIBRIUM; GENETIC PATHWAY; MIXED MODELS; REGRESSION; TESTS; CANCER; HAPLOTYPES; SIMILARITY; POWER AB In this article, we develop a powerful test for identifying single nucleotide polymorphism (SNP)-sets that are predictive of survival with data from genome-wide association studies. We first group typed SNPs into SNP-sets based on genomic features and then apply a score test to assess the overall effect of each SNP-set on the survival outcome through a kernel machine Cox regression framework. This approach uses genetic information from all SNPs in the SNP-set simultaneously and accounts for linkage disequilibrium (LD), leading to a powerful test with reduced degrees of freedom when the typed SNPs are in LD with each other. This type of test also has the advantage of capturing the potentially nonlinear effects of the SNPs, SNP-SNP interactions (epistasis), and the joint effects of multiple causal variants. By simulating SNP data based on the LD structure of real genes from the HapMap project, we demonstrate that our proposed test is more powerful than the standard single SNP minimum P-value-based test for association studies with censored survival outcomes. We illustrate the proposed test with a real data application. Genet. Epidemiol. 35:620-631, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Lin, Xinyi; Cai, Tianxi; Zhou, Qian; Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Wu, Michael C.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Liu, Geoffrey] Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Lin, XH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM xlin@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016; OI Wu, Michael C./0000-0002-3357-6570 FU National Institutes of Health [R37 CA076404, P01 CA134294, R01 CA092824, R01 CA074386, P50 CA090578, P42 ES016454, P30 ES00002, R01 GM079330]; National Science Foundation [DMS 0854970] FX This research is supported by National Institutes of Health grants R37 CA076404 (X.L.), P01 CA134294 (X.L.), R01 CA092824 (D.C.C), R01 CA074386 (D.C.C), P50 CA090578 (D.C.C), P42 ES016454 (X.L and D.C.C), P30 ES00002 (X.L and D.C.C), R01 GM079330 (T.C.) and National Science Foundation grant DMS 0854970 (T.C.). NR 30 TC 23 Z9 23 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2011 VL 35 IS 7 BP 620 EP 631 DI 10.1002/gepi.20610 PG 12 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 845TT UT WOS:000296846900005 PM 21818772 ER PT J AU Coticchia, CM Curatolo, AS Zurakowski, D Yang, J Daniels, KE Matulonis, UA Moses, MA AF Coticchia, Christine M. Curatolo, Adam S. Zurakowski, David Yang, Jiang Daniels, Kathryn E. Matulonis, Ursula A. Moses, Marsha A. TI Urinary MMP-2 and MMP-9 predict the presence of ovarian cancer in women with normal CA125 levels SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Biomarkers; Matrix metalloproteinases; Neutrophil gelatinase-associated lipocalin ID CA-125 LEVELS; LIPOCALIN 2; THERAPY; METALLOPROTEINASES; PROGRESSION; BIOMARKERS; MARKERS; ASSAY AB Objective. To determine whether urinary matrix metalloproteinases (MMPs) predict the presence of ovarian cancer in patients with CA125 levels below the normal threshold of 35 U/mL, a critical group of patients for whom no ovarian cancer biomarker is currently available. To determine whether these noninvasive biomarkers provide clinically useful information in the general ovarian cancer patient population as well. Methods. ELISA analyses and substrate gel electrophoresis detected the levels and activity of urinary MMP-2, MMP-9, MMP-9/neutrophil gelatinase-associated lipocalin (NGAL) complex, and MMP-9 dimer in all ovarian cancer patients (n = 97), those with CA125 <35 U/mL (n = 26) and controls (n = 81). Results. In patients with CA125 <35 U/mL, receiver-operating characteristic (ROC) area under curve (AUC) analysis demonstrated that either urinary MMP-2 or MMP-9 or NGAL significantly discriminated between controls and ovarian cancer patients with normal CA125. Multivariate logistic regression revealed that the combination of urinary MMP-2 and MMP-9 provided the best diagnostic accuracy when multiplexed. When further multiplexed with age, the diagnostic accuracy of these biomarkers increased to a significant AUC of 0.820. These findings were consistent among the general ovarian cancer population studied as well, where the combination of urinary MMP-2 and MMP-9 multiplexed with age resulted in a highly significant AUC of 0.881. Pearson chi-square analysis revealed that higher urinary levels of either MMP-2 or MMP-9 were strongly associated with the increasing percentage of women with ovarian cancer independent of CA125 levels. Conclusion. This study demonstrates the potential utility of urinary MMP-2 and MMP-9 to differentiate between ovarian cancer patients with normal CA125 levels and controls and suggests that urinary MMP-2 and MMP-9 may be a clinically useful aid in the diagnosis of advanced or recurrent ovarian cancer. (C) 2011 Elsevier Inc. All rights reserved. C1 [Coticchia, Christine M.; Curatolo, Adam S.; Yang, Jiang; Moses, Marsha A.] Childrens Hosp Boston, Program Vasc Biol, Boston, MA 02115 USA. [Coticchia, Christine M.; Curatolo, Adam S.; Yang, Jiang; Moses, Marsha A.] Childrens Hosp Boston, Dept Surg, Boston, MA 02115 USA. [Coticchia, Christine M.; Yang, Jiang; Moses, Marsha A.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Zurakowski, David] Childrens Hosp Boston, Dept Anesthesiol, Boston, MA 02115 USA. [Daniels, Kathryn E.; Matulonis, Ursula A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Matulonis, Ursula A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Moses, MA (reprint author), Childrens Hosp Boston, Program Vasc Biol, Karp Family Res Bldg,Room 12129,300 Longwood Ave, Boston, MA 02115 USA. EM marsha.moses@childrens.harvard.edu FU Ovations for the Cure of Ovarian Cancer; Stuart Weitzman Foundation; Advanced Medical Research Foundation; Lillian E. Tymkewicz Memorial Fund FX The authors gratefully acknowledge the support of Ovations for the Cure of Ovarian Cancer (UAM and MAM), the Stuart Weitzman Foundation, Advanced Medical Research Foundation and the Lillian E. Tymkewicz Memorial Fund. NR 28 TC 17 Z9 21 U1 0 U2 6 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 NOV PY 2011 VL 123 IS 2 BP 295 EP 300 DI 10.1016/j.ygyno.2011.07.034 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 839ZJ UT WOS:000296407700022 PM 21889192 ER PT J AU Carroll, A Thompson, MS Co, C Zaid, TM Wong, KK Yeung, TL Schmandt, R Birrer, MJ Mok, SC AF Carroll, A. Thompson, M. S. Co, C. Zaid, T. M. Wong, K. K. Yeung, T. L. Schmandt, R. Birrer, M. J. Mok, S. C. TI Overexpression of stromal biglycan correlates with improved survival in patients with high-grade serous ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Carroll, A.; Thompson, M. S.; Co, C.; Zaid, T. M.; Wong, K. K.; Yeung, T. L.; Schmandt, R.; Mok, S. C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Birrer, M. J.; Mok, S. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2011 VL 123 IS 2 BP 438 EP 438 DI 10.1016/j.ygyno.2011.07.060 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 839ZJ UT WOS:000296407700072 ER PT J AU Corey, KE Chalasani, N AF Corey, Kathleen E. Chalasani, Naga TI Should Combination Therapy Be the Paradigm for Future Nonalcoholic Steatohepatitis Clinical Trials? SO HEPATOLOGY LA English DT Editorial Material ID FATTY LIVER-DISEASE; VITAMIN-E; ANTAGONIST; LOSARTAN; RATS; CCL4 C1 [Chalasani, Naga] Indiana Univ Sch Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA. [Corey, Kathleen E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gastroenterol & Hepatol, Cambridge, MA 02138 USA. RP Chalasani, N (reprint author), Indiana Univ Sch Med, Div Gastroenterol & Hepatol, RG 4100,1050 Wishard Blvd, Indianapolis, IN 46202 USA. EM nchalasa@iupui.edu FU NIDDK NIH HHS [K24 DK069290] NR 11 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2011 VL 54 IS 5 BP 1503 EP 1505 DI 10.1002/hep.24696 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 840LX UT WOS:000296443100004 PM 21953015 ER PT J AU Golden-Mason, L Bambha, KM Cheng, LL Howell, CD Taylor, MW Clark, PJ Afdhal, N Rosen, HR AF Golden-Mason, Lucy Bambha, Kiran M. Cheng, Linling Howell, Charles D. Taylor, Milton W. Clark, Paul J. Afdhal, Nezam Rosen, Hugo R. CA Virahep-C Study Grp TI Natural Killer Inhibitory Receptor Expression Associated with Treatment Failure and Interleukin-28B Genotype in Patients with Chronic Hepatitis C SO HEPATOLOGY LA English DT Article ID VIRUS-INFECTION; TREATMENT RESPONSE; ANTIVIRAL THERAPY; GENE-EXPRESSION; INTERFERON; IL28B; RIBAVIRIN; CELLS; PEGINTERFERON; PREDICTS AB Natural killer (NK) cells constitute a first line of defense against viral infections; their function is governed by the integration of signals from multiple activating and inhibitory surface receptors. We hypothesized that because NKs become rapidly activated by cytokines, response to anti-hepatitis C virus (HCV) therapy would be predicted by the phenotype and function of NKs. We used a cohort of 101 patients (55 African, 46 Caucasian-American) who received pegylated-interferon (IFN) and ribavirin for 48 weeks. Multi-parameter FACS analysis was used to examine relative expression of 14 different inhibitory/activating receptors. Interleukin (IL)-28B genotyping (rs12979860) was also performed. Pretreatment levels of inhibitory receptors CD158a, CD158b, and CD158e were higher in patients who demonstrated poor viral decline within the first 28 days of therapy. Higher expression levels of inhibitory receptors NKG2A, CD158b, and CD158e were demonstrable in patients who failed to achieve sustained virologic response (SVR). Patients carrying the IL-28B T allele had higher NKG2A expression on effector NKs. We created a mathematical regression model incorporating race, viral level, and two inhibitory receptors. The area-under-the curve was 0.88, which is highly predictive of SVR. Moreover, the model performed complementarily with IL-28B across the CC, CT, and TT genotypes. Purified NKG2A neg NKs treated with pegylated-IFN-alpha for 4 hours demonstrated higher levels of IFN-c-inducible protein-10 (IP-10) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) compared with their NKG2A(pos) counterparts. Conclusions: These results provide novel insights into the associations of NK phenotype with IL-28B genotype and gene expression patterns, as well as the role of NKs in mediating IFN-induced viral clearance of chronic HCV infection. (HEPATOLOGY 2011;54:1559-1569) C1 [Golden-Mason, Lucy; Bambha, Kiran M.; Cheng, Linling; Rosen, Hugo R.] Univ Colorado, Dept Med, Div Gastroenterol & Hepatol, Hepatitis Ctr C, Denver, CO USA. [Golden-Mason, Lucy; Bambha, Kiran M.; Cheng, Linling; Rosen, Hugo R.] Natl Jewish Hosp, Denver, CO USA. [Golden-Mason, Lucy] Univ Colorado, Integrated Program Immunol, Denver, CO 80202 USA. [Howell, Charles D.] Univ Maryland, Baltimore Sch Med, Baltimore, MD 21201 USA. [Taylor, Milton W.] Indiana Univ, Dept Biol, Bloomington, IN USA. [Clark, Paul J.] Duke Univ, Med Ctr, Sch Med, Div Gastroenterol, Durham, NC 27710 USA. [Clark, Paul J.] Duke Clin Res Inst, Durham, NC USA. [Afdhal, Nezam] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Rosen, Hugo R.] Denver VA Med Ctr, Denver, CO USA. RP Rosen, HR (reprint author), Div GI Hepatol B 158, Acad Off Bldg 1,12631 E 17th Ave,Rm 7614,POB 6511, Aurora, CO 80045 USA. EM hugo.rosen@ucdenver.edu RI Clark, Paul/A-1480-2012 OI Clark, Paul/0000-0002-1821-4969 FU NIDDK [1 K24 DK072036-01]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Cancer Institute (NCI) with Roche Laboratories, Inc.; National Health and Medical Research Council of Australia; Duke Clinical Research Institute; Richard Boebel Family Fund; National Centre in HIV Epidemiology and Clinical Research (now the Kirby Institute for Infection and Immunity in Society), University of New South Wales, Australia; [RO1 DK071560]; [U01 DK60329]; [U01 DK60340]; [U01 DK60324]; [U01 DK60344]; [U01 DK60327]; [U01 DK60335]; [U01 DK60352]; [U01 DK60342]; [U01 DK60345]; [U01 DK60309]; [U01 K60346]; [U01 DK60349]; [U01 DK60341] FX Supported by RO1 DK071560 (to H. R. R.) and by NIDDK 1 K24 DK072036-01. (to. C. D. H). This study was funded as a cooperative agreement by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Intramural Research Program of the National Cancer Institute (NCI) with further support under a Cooperative Research and Development Agreement (CRADA) with Roche Laboratories, Inc. A complete listing of participants in the Virahep-C study is given in Reference 5. Grant numbers: U01 DK60329, U01 DK60340, U01 DK60324, U01 DK60344, U01 DK60327, U01 DK60335, U01 DK60352, U01 DK60342, U01 DK60345, U01 DK60309, U01 DK60346, U01 DK60349, U01 DK60341. Dr. Howell is supported by NIDDK 1 K24 DK072036-01. Dr. Clark received funding support from the National Health and Medical Research Council of Australia, the Duke Clinical Research Institute, the Richard Boebel Family Fund, the National Centre in HIV Epidemiology and Clinical Research (now the Kirby Institute for Infection and Immunity in Society), University of New South Wales, Australia. NR 26 TC 41 Z9 45 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2011 VL 54 IS 5 BP 1559 EP 1569 DI 10.1002/hep.24556 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 840LX UT WOS:000296443100010 PM 21983945 ER PT J AU Foster, MC Hwang, SJ Porter, SA Massaro, JM Hoffmann, U Fox, CS AF Foster, Meredith C. Hwang, Shih-Jen Porter, Stacy A. Massaro, Joseph M. Hoffmann, Udo Fox, Caroline S. TI Fatty Kidney, Hypertension, and Chronic Kidney Disease The Framingham Heart Study SO HYPERTENSION LA English DT Article DE renal sinus fat; hypertension; chronic kidney disease; blood pressure; computed tomography; epidemiology ID GLOMERULAR-FILTRATION-RATE; SERUM CYSTATIN-C; OBESITY-INDUCED HYPERTENSION; RENAL-VEIN CONSTRICTION; METABOLIC SYNDROME; ADIPOSE-TISSUE; BLOOD-PRESSURE; RISK-FACTORS; ASSOCIATION; CREATININE AB Ectopic fat depots may mediate local and systemic disease. Animal models of diet-induced obesity demonstrate increased fat accumulation in the renal sinus. The association of renal sinus fat with hypertension, chronic kidney disease, and other metabolic disorders has not been studied in a large, community-based sample. Participants from the Framingham Heart Study (n = 2923; mean age: 54 years; 51% women) underwent quantification of renal sinus fat area using computed tomography. High renal sinus fat ("fatty kidney") was defined using sex-specific 90th percentiles in a healthy referent subsample. Multivariable linear and logistic regression was used to model metabolic risk factors as a function of fatty kidney and log-transformed renal sinus fat. Multivariable models were adjusted for age, sex, and outcome-specific covariates and then additionally adjusted for body mass index or abdominal visceral adipose tissue. The prevalence of fatty kidney was 30.1% (n = 879). Individuals with fatty kidney had a higher odds ratio (OR) of hypertension (OR: 2.12; P < 0.0001), which persisted after adjustment for body mass index (OR: 1.49; P < 0.0001) or visceral adipose tissue (OR: 1.24; P = 0.049). Fatty kidney was also associated with an increased OR for chronic kidney disease (OR: 2.30; P = 0.005), even after additionally adjusting for body mass index (OR: 1.86; P = 0.04) or visceral adipose tissue (OR: 1.86; P = 0.05). We observed no association between fatty kidney and diabetes mellitus after adjusting for visceral adipose tissue. In conclusion, fatty kidney is a common condition that is associated with an increased risk of hypertension and chronic kidney disease. Renal sinus fat may play a role in blood pressure regulation and chronic kidney disease. (Hypertension. 2011;58:784-790.). Online Data Supplement C1 [Foster, Meredith C.; Hwang, Shih-Jen; Fox, Caroline S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Foster, Meredith C.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Foster, Meredith C.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA. [Foster, Meredith C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA. [Porter, Stacy A.] Harvard Univ, Sch Med, Boston, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung, and Blood Institute [N01-HC-25195] FX The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute (N01-HC-25195). NR 42 TC 74 Z9 77 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2011 VL 58 IS 5 BP 784 EP U266 DI 10.1161/HYPERTENSIONAHA.111.175315 PG 15 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 842HQ UT WOS:000296588100644 PM 21931075 ER PT J AU Hill, CA Litvak, A Canapari, C Cummings, B Collins, C Keamy, DG Ferris, TG Hartnick, CJ AF Hill, Courtney A. Litvak, Andrea Canapari, Craig Cummings, Brian Collins, Corey Keamy, Donald G. Ferris, Timothy G. Hartnick, Christopher J. TI A pilot study to identify pre- and peri-operative risk factors for airway complications following adenotonsillectomy for treatment of severe pediatric OSA SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Pediatrics; Sleep apnea ID OBSTRUCTIVE SLEEP-APNEA; CLINICAL-PRACTICE GUIDELINE; QUALITY-OF-LIFE; RESPIRATORY COMPLICATIONS; CHILDREN; TONSILLECTOMY; BEHAVIOR AB Objective: A pilot study to identify risk factors predicting post-operative complications in children with severe OSA undergoing adenotonsillectomy. Methods: Retrospective review in a tertiary care academic institution. Two-stage least squares regression analysis and instrumental variable analysis to allow for modeling of pre- and peri-operative risk factors as having significance in predicting post-operative morbidity. Results: Eighty-three children (mean age 4.88 +/- 3.09 years) with apnea-hypopnea index (AHI) >= 10 who were observed overnight following adenotonsillectomy were evaluated for rates of major (increased level of care, CPAP/BiPAP use, pulmonary edema and reintubation) and minor (oxygen saturation <90%) airway complications as well as total observation costs. Major and minor complications occurred in 4.8% and 19.3% of children, respectively. Age <2 years (p < 0.01), AHI > 24 (p < 0.05), intra-operative laryngospasm requiring treatment (p < 0.05). oxygen saturations <90% on room air in PACU (p < 0.05) and PACU stay >100 min (p < 0.01) independently predicted post-operative complications. Children with any one of these factors experienced a 38% complication rate versus 4% in all others. Conclusions: This pilot study identified pre- and peri-operative risk factors that collectively can be investigated as predictors of post-operative airway complications in a prospective study. By identifying preliminary results comparing the complication rates between those children with and without these risk factors, we will be able to calculate the sample size for a future prospective validation study. Such a study is necessary to understand the safety and potential significant cost savings of observing children without risk factors on the pediatric floor and not in an ICU setting. A best practice algorithm can be created for children with severe OSA only after completing this prospective study. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Hill, Courtney A.; Keamy, Donald G.; Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. [Litvak, Andrea] Massachusetts Gen Hosp, Massachusetts Gen Phys Org, Boston, MA 02114 USA. [Canapari, Craig; Cummings, Brian] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Collins, Corey] Harvard Univ, Sch Med, Dept Anesthesiol, Cambridge, MA 02138 USA. [Ferris, Timothy G.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Ferris, Timothy G.] Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu NR 30 TC 19 Z9 20 U1 0 U2 3 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 NOV PY 2011 VL 75 IS 11 BP 1385 EP 1390 DI 10.1016/j.ijporl.2011.07.034 PG 6 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 843PQ UT WOS:000296684800008 PM 21871668 ER PT J AU Sachs, G AF Sachs, Gary TI Why Do Clinical Trials Fail? Learning from Computer Administered Assessments SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN CLINICAL PRACTICE LA English DT Meeting Abstract C1 [Sachs, Gary] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sachs, Gary] Bracket, Lexington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1365-1501 J9 INT J PSYCHIAT CLIN JI Int. J. Psychiat. Clin. PD NOV PY 2011 VL 15 SU 2 BP 12 EP 13 PG 2 WC Psychiatry SC Psychiatry GA 844WD UT WOS:000296780400028 ER PT J AU Dastjerdi, MH Sadrai, Z Saban, DR Zhang, Q Dana, R AF Dastjerdi, Mohammad H. Sadrai, Zahra Saban, Daniel R. Zhang, Qiang Dana, Reza TI Corneal Penetration of Topical and Subconjunctival Bevacizumab SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID INTRAVITREAL BEVACIZUMAB; ANTIBODY FRAGMENTS; NEOVASCULARIZATION; AVASTIN; INJECTION; INHIBITION; EYE; ANGIOGENESIS; OCCLUSION; DELIVERY AB PURPOSE. To investigate the ability of bevacizumab to penetrate the cornea after topical application or subconjunctival injection. METHODS. Bevacizumab 1% was topically applied three times a day to the corneas of mice (BALB/c) with intact corneas (n = 14), and with corneal neovascularization (n = 14). Animals were euthanized at 1, 6, 12, and 24 hours, and 2, 4, and 7 days for immunohistochemical analyses. Donkey anti-human IgG labeled with Cy3 was used for bevacizumab immunoreactivity detection. Additionally, one-time topical bevacizumab 1% was tested in corneas with denuded epithelium (n = 16). In another group (n = 16), a single dose of 0.5 mg bevacizumab was injected subconjunctivally. Animals were euthanized at 1, 6, and 24 hours, and 2, 4, 7, 14, and 21 days for immunohistochemical studies. RESULTS. Bevacizumab was barely detected beyond the very superficial layer of the corneal epithelium in mice with intact corneas even after 7 days of topical administration. Application of bevacizumab in mice with corneal neovascularization; however, showed variable penetration into the corneal stroma. Experimentation with single application of topical bevacizumab in corneas with denuded epithelium or subconjunctivally injected bevacizumab showed intense staining for bevacizumab. CONCLUSIONS. Topically applied bevacizumab has limited capacity to penetrate the corneas with intact epithelium. However, bevacizumab can penetrate the neovascularized cornea after topical application. This study demonstrates that subconjunctivally injected bevacizumab in eyes with an intact cornea penetrates well into the corneal stroma. (Invest Ophthalmol Vis Sci. 2011;52:8718-8723) DOI: 10.1167/iovs.11-7871 C1 [Dastjerdi, Mohammad H.; Sadrai, Zahra; Saban, Daniel R.; Zhang, Qiang; Dana, Reza] Schepens Eye Res Inst, Boston, MA 02114 USA. [Dastjerdi, Mohammad H.; Sadrai, Zahra; Saban, Daniel R.; Zhang, Qiang; Dana, Reza] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Dastjerdi, Mohammad H.; Dana, Reza] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dana, R (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU NIH [EY12963, EY19098] FX Supported in part by NIH Grants EY12963 and EY19098. NR 27 TC 42 Z9 43 U1 0 U2 7 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 NOV PY 2011 VL 52 IS 12 BP 8718 EP 8723 DI 10.1167/iovs.11-7871 PG 6 WC Ophthalmology SC Ophthalmology GA 844PW UT WOS:000296760700022 PM 22003112 ER PT J AU Aronis, KN Vamvini, MT Chamberland, JP Mantzoros, CS AF Aronis, Konstantinos N. Vamvini, Maria T. Chamberland, John P. Mantzoros, Christos S. TI Circulating Clusterin (Apolipoprotein J) Levels Do Not Have Any Day/Night Variability and Are Positively Associated with Total and LDL Cholesterol Levels in Young Healthy Individuals SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TYPE-2 DIABETES-MELLITUS; CORONARY-HEART-DISEASE; LEPTIN; ADIPONECTIN; NEUROENDOCRINE; PURIFICATION; CANCER; MEN; CLU AB Context: Clusterin has been associated with several pathologies, including cardiovascular disease and neoplasias. However, little is known about its physiology and its association with metabolic and anthropometric parameters in humans. Objective: The aim of the study was to examine whether circulating clusterin levels exhibit a day/night variation pattern and whether clusterin is associated with anthropometric and metabolic parameters. Design: Study A was a frequent sampling study to evaluate potential periodicity in clusterin secretion. Study B was an observational study to evaluate the cross-sectional and prospective associations of clusterin with anthropometric and metabolic parameters. Participants: Study A participants were healthy males (n = 6) and females (n = 6), aged 22.3 +/- 3.1 and 22.8 +/- 3.4 yr, respectively. Study B participants were 186 healthy males aged 18.4 +/- 0.14 yr. Ninety-one of the study B subjects were studied again 2 yr later and clusterin's associations with change of anthropometric and metabolic parameters were thus investigated prospectively. Intervention: Samples in study A were collected every 15 min during an overnight admission, and subsequently pooled every hour. Samples in study B were collected during a screening visit. Main Outcome Measure: Circulating clusterin levels were measured. Results: In study A, spectral domain and cosinor regression analysis failed to reveal any day/night variation pattern. In study B, clusterin was positively correlated with total and low-density lipoprotein cholesterol (r = 0.23, P = 0.002; and r = 0.20, P = 0.005). Baseline clusterin did not predict change of any anthropometric, biochemical, or metabolic parameters prospectively. Conclusions: We report for the first time that circulating clusterin does not have a day/night variation pattern in healthy young individuals. Clusterin levels are associated with total and low-density lipoprotein cholesterol cross-sectionally but do not predict short-term changes in metabolic parameters in healthy young males. (J Clin Endocrinol Metab 96: E1871-E1875, 2011) C1 [Aronis, Konstantinos N.; Vamvini, Maria T.; Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Dept Internal Med,Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Endocrinol Sect, Sch Med, Dept Internal Med,VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Dept Internal Med,Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Stoneman 816, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Aronis, Konstantinos/F-3586-2012; OI Aronis, Konstantinos/0000-0001-7189-8434; Chamberland, John/0000-0002-7862-1371 FU National Center for Research Resources [M01-RR-01032-328840]; National Institute of Diabetes and Digestive and Kidney Diseases [DK058785, DK079929, DK081913]; National Institute on Aging [AG032030]; VA Merit award FX This work was supported by National Center for Research Resources Grant M01-RR-01032-328840 (to the Harvard Clinical and Translational Science Center). 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. Funding was also received from the National Institute of Diabetes and Digestive and Kidney Diseases (Grants DK058785, DK079929, and DK081913), the National Institute on Aging (Grant AG032030), and a VA Merit award. NR 20 TC 1 Z9 2 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 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2011 VL 96 IS 11 BP E1871 EP E1875 DI 10.1210/jc.2011-1555 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 844MF UT WOS:000296750600022 PM 21900379 ER PT J AU Chan, YM Broder-Fingert, S Paraschos, S Lapatto, R Au, M Hughes, V Bianco, SDC Min, L Plummer, L Cerrato, F De Guillebon, A Wu, IH Wahab, F Dwyer, A Kirsch, S Quinton, R Cheetham, T Ozata, M Ten, S Chanoine, JP Pitteloud, N Martin, KA Schiffmann, R Van der Kamp, HJ Nader, S Hall, JE Kaiser, UB Seminara, SB AF Chan, Yee-Ming Broder-Fingert, Sarabeth Paraschos, Sophia Lapatto, Risto Au, Margaret Hughes, Virginia Bianco, Suzy D. C. Min, Le Plummer, Lacey Cerrato, Felecia De Guillebon, Adelaide Wu, I-Hsuan Wahab, Fazal Dwyer, Andrew Kirsch, Susan Quinton, Richard Cheetham, Timothy Ozata, Metin Ten, Svetlana Chanoine, Jean-Pierre Pitteloud, Nelly Martin, Kathryn A. Schiffmann, Raphael Van der Kamp, Hetty J. Nader, Shahla Hall, Janet E. Kaiser, Ursula B. Seminara, Stephanie B. TI GnRH-Deficient Phenotypes in Humans and Mice with Heterozygous Variants in KISS1/Kiss1 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; CENTRAL PRECOCIOUS PUBERTY; KALLMANN-SYNDROME; RECEPTOR GPR54; KISS1 GENE; MUTATIONS; PROTEIN; PROKINETICIN-2; POLYMORPHISMS AB Context: KISS1 is a candidate gene for GnRH deficiency. Objective: Our objective was to identify deleterious mutations in KISS1. Patients and Methods: DNA sequencing and assessment of the effects of rare sequence variants (RSV) were conducted in 1025 probands with GnRH-deficient conditions. Results: Fifteen probands harbored 10 heterozygous RSV in KISS1 seen in less than 1% of control subjects. Of the variants that reside within the mature kisspeptin peptide, p.F117L (but not p.S77I, p.Q82K, p.H90D, or p.P110T) reduces inositol phosphate generation. Of the variants that lie within the coding region but outside the mature peptide, p.G35S and p.C53R (but not p.A129V) are predicted in silico to be deleterious. Of the variants that lie outside the coding region, one (g.13659C -> T) impairs transcription in vitro, and another (c.1-7C -> T) lies within the consensus Kozak sequence. Of five probands tested, four had abnormal baseline LH pulse patterns. In mice, testosterone decreases with heterozygous loss of Kiss1 and Kiss1r alleles (wild-type, 274 +/- 99, to double heterozygotes, 69 +/- 16 ng/dl; r(2) = 0.13; P = 0.03). Kiss1/Kiss1r double-heterozygote males have shorter anogenital distances (13.0 +/- 0.2 vs. 15.6 +/- 0.2 mm at P34, P < 0.001), females have longer estrous cycles (7.4 +/- 0.2 vs. 5.6 +/- 0.2 d, P < 0.01), and mating pairs have decreased litter frequency (0.59 +/- 0.09 vs. 0.71 +/- 0.06 litters/month, P < 0.04) and size (3.5 +/- 0.2 vs. 5.4 +/- 0.3 pups/litter, P < 0.001) compared with wild-type mice. Conclusions: Deleterious, heterozygous RSV in KISS1 exist at a low frequency in GnRH-deficient patients as well as in the general population in presumably normal individuals. As in Kiss1(+/-)/Kiss1r(+/-) mice, heterozygous KISS1 variants in humans may work with other genetic and/or environmental factors to cause abnormal reproductive function. (J Clin Endocrinol Metab 96: E1771-E1781, 2011) C1 [Chan, Yee-Ming; Broder-Fingert, Sarabeth; Paraschos, Sophia; Lapatto, Risto; Au, Margaret; Hughes, Virginia; Plummer, Lacey; Cerrato, Felecia; De Guillebon, Adelaide; Wu, I-Hsuan; Wahab, Fazal; Dwyer, Andrew; Pitteloud, Nelly; Martin, Kathryn A.; Hall, Janet E.; Seminara, Stephanie B.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Chan, Yee-Ming; Broder-Fingert, Sarabeth; Paraschos, Sophia; Lapatto, Risto; Au, Margaret; Hughes, Virginia; Plummer, Lacey; Cerrato, Felecia; De Guillebon, Adelaide; Wu, I-Hsuan; Wahab, Fazal; Dwyer, Andrew; Pitteloud, Nelly; Martin, Kathryn A.; Hall, Janet E.; Seminara, Stephanie B.] Massachusetts Gen Hosp, Harvard Ctr Reprod Sci, Dept Med, Boston, MA 02114 USA. [Chan, Yee-Ming] Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. [Bianco, Suzy D. C.; Min, Le; Kaiser, Ursula B.] Brigham & Womens Hosp, Harvard Ctr Reprod Sci, Boston, MA 02115 USA. [Bianco, Suzy D. C.; Min, Le; Kaiser, Ursula B.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kirsch, Susan] Hosp Sick Children, Dept Endocrinol, Toronto, ON M5G 1X8, Canada. [Quinton, Richard; Cheetham, Timothy] Newcastle Univ, Inst Human Genet, Endocrinol Res Grp, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. [Ozata, Metin] Gulhane Mil Med Acad, Dept Endocrinol, TR-06018 Ankara, Turkey. [Ten, Svetlana] Maimonides Infants & Childrens Hosp, Dept Pediat, Div Endocrinol, Brooklyn, NY 11219 USA. [Chanoine, Jean-Pierre] Univ British Columbia, Dept Pediat, Endocrinol & Diabet Unit, Vancouver, BC V6H 3V4, Canada. [Schiffmann, Raphael] Inst Metab Dis, Dallas, TX 75226 USA. [Van der Kamp, Hetty J.] Leiden Univ, Med Ctr, Dept Pediat, Leiden, Netherlands. [Nader, Shahla] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Div Endocrinol, Houston, TX 77030 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Bartlett Hall Extens 504,55 Fruit St, Boston, MA 02114 USA. EM seminara.stephanie@mgh.harvard.edu RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014; Wahab, Fazal/G-2478-2012; OI Dwyer, Andrew/0000-0002-7023-6794; Broder-Fingert, Sarabeth/0000-0002-0932-4461 FU National Institutes of Health (NIH) [R01 HD015788]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD [M01-RR-01066]; Harvard Clinical and Translational Science Center, from the National Center for Research Resources [T32 DK007529]; National Institute of Diabetes and Digestive and Kidney Disorders [U54HD028138]; Specialized Cooperative Center, NICHD [K12 HD051959] FX This work was supported by National Institutes of Health (NIH) Grants R01 HD015788 (Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD), M01-RR-01066 (Harvard Clinical and Translational Science Center, from the National Center for Research Resources), T32 DK007529 (National Institute of Diabetes and Digestive and Kidney Disorders), U54HD028138(through cooperative agreement as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research, NICHD), and K12 HD051959 (as part of the Building Interdisciplinary Research Careers in Women's Health program, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, HICHD, and Office of the Director). NR 45 TC 25 Z9 25 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 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2011 VL 96 IS 11 BP E1771 EP E1781 DI 10.1210/jc.2011-0518 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 844MF UT WOS:000296750600007 PM 21880801 ER PT J AU Yu, EW Kumbhani, R Siwila-Sackman, E Leder, BZ AF Yu, Elaine W. Kumbhani, Ruchit Siwila-Sackman, Erica Leder, Benjamin Z. TI Acute Decline in Serum Sclerostin in Response to PTH Infusion in Healthy Men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PARATHYROID-HORMONE; PRIMARY HYPERPARATHYROIDISM; POSTMENOPAUSAL WOMEN; SKELETAL SENSITIVITY; BONE ENHANCER; ESTROGEN; SOST; OSTEOCYTES; DISEASE AB Context: Animal models suggest that the osteoblast-stimulating actions of PTH are mediated by acute suppression of sclerostin, an inhibitor of the anabolic Wnt pathway. The immediate physiological changes in serum sclerostin in response to PTH infusion have not been reported in human studies. Objective: We sought to determine the acute physiological effects of PTH infusion on serum sclerostin and bone turnover markers in healthy adult men. Design, Setting, and Participants: Fifty-three healthy adult men underwent an 18-h iv infusion of human PTH(1-34) at a dose of 0.55 U/kg . h. Outcomes: Serum levels of ionized calcium, sclerostin, and markers of bone formation (osteocalcin and amino-terminal propeptide of type I procollagen) and bone resorption (C-telopeptide and N-telopeptide) were obtained at 0, 6, 12, and 18 h. Results: Serum ionized calcium, C-telopeptide, and N-telopeptide increased, and osteocalcin and amino-terminal propeptide of type I procollagen fell linearly throughout the PTH infusion (P < 0.001 for all). Average +/- SEM sclerostin levels declined from 936 +/- 65 to 813 +/- 63 pg/ml at 6 h (P < 0.001) and remained stably suppressed for the duration of the PTH infusion. There were no significant correlations between change in sclerostin and change in bone markers. Conclusions: Serum sclerostin declined in response to acute PTH infusion within 6 h in healthy adult men. The early plateau in sclerostin suppression may indicate that maximal stimulation of the Wnt pathway is achieved quickly after exposure to PTH. Our findings support the hypothesis that PTH may mediate its anabolic effects in part via suppression of sclerostin. (J Clin Endocrinol Metab 96: E1848-E1851, 2011) C1 [Yu, Elaine W.; Kumbhani, Ruchit; Siwila-Sackman, Erica; Leder, Benjamin Z.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Yu, EW (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier 1051, Boston, MA 02114 USA. EM ewyu@partners.org FU National Institutes of Health [K23-RR16310]; Massachusetts General Hospital Clinical Research Center [RR-1066] FX This work was supported by National Institutes of Health Grants K23-RR16310 and Massachusetts General Hospital Clinical Research Center Grant RR-1066. NR 19 TC 28 Z9 28 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 NOV PY 2011 VL 96 IS 11 BP E1848 EP E1851 DI 10.1210/jc.2011-1534 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 844MF UT WOS:000296750600017 PM 21865370 ER PT J AU Pellegrini, CN Scheinman, MM Badhwar, N AF Pellegrini, Cara N. Scheinman, Melvin M. Badhwar, Nitish TI Idiopathic epicardial ventricular tachycardia with origin remote from vascular structures SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Idiopathic ventricular tachycardia; Epicardial; Perivascular; Catheter ablation ID CATHETER ABLATION; OUTFLOW TRACT; IDENTIFY; VALSALVA; SINUS; SITE AB We report a case of a patient with idiopathic left ventricular tachycardia (VT) successfully ablated from the epicardial aspect of the left ventricle, after a previous failed endocardial ablation. The VT appeared to be catecholamine sensitive. An excellent epicardial pacemap was found in the midlateral region of the left ventricle, remote from vascular structures. Following ablation, the patient discontinued antiarrhythmic drug use and has not experienced any recurrence of VT for more than 2 1/2 years. (C) 2011 Elsevier Inc. All rights reserved. C1 [Pellegrini, Cara N.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Pellegrini, Cara N.; Scheinman, Melvin M.; Badhwar, Nitish] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Pellegrini, CN (reprint author), San Francisco VA Med Ctr, Dept Med, 4150 Clement St,111C, San Francisco, CA 94121 USA. EM pellegrinic@medicine.ucsf.edu FU American Heart Association FX Supported in part by a grant from the American Heart Association NR 13 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD NOV-DEC PY 2011 VL 44 IS 6 BP 792 EP 795 DI 10.1016/j.jelectrocard.2011.01.007 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 843GO UT WOS:000296660500031 PM 21419422 ER PT J AU Eswara, JR Gervais, DA Mueller, PR Cantwell, CP Uppot, RN McGovern, FJ AF Eswara, Jairam R. Gervais, Debra A. Mueller, Peter R. Cantwell, Colin P. Uppot, Raul N. McGovern, Francis J. TI OUTCOMES OF RENAL RADIOFREQUENCY ABLATION WITH PYELOPERFUSION SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Eswara, Jairam R.; McGovern, Francis J.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Gervais, Debra A.; Mueller, Peter R.; Cantwell, Colin P.; Uppot, Raul N.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD NOV PY 2011 VL 25 SU 1 BP A134 EP A134 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 844ZI UT WOS:000296792200408 ER PT J AU Eswara, JR Sharif-Tabrizi, A Sacco, D AF Eswara, Jairam R. Sharif-Tabrizi, Ahmad Sacco, Dianne TI POSITIVE STONE CULTURE IS ASSOCIATED WITH UROSEPSIS AFTER ENDOUROLOGICAL PROCEDURES - AN UPDATE SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Eswara, Jairam R.; Sharif-Tabrizi, Ahmad; Sacco, Dianne] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD NOV PY 2011 VL 25 SU 1 BP A45 EP A46 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 844ZI UT WOS:000296792200144 ER PT J AU Londono, DC Wuerstle, M Thomas, AA Tsu, JW Danial, T Chien, G AF Londono, Diana C. Wuerstle, Melanie Thomas, Anil A. Tsu, Jin-Wen Danial, Tarek Chien, Gary TI ACCURACY AND IMPLICATION OF PERCUTANEOUS RENAL BIOPSY IN THE MANAGEMENT OF RENAL MASSES SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Londono, Diana C.; Wuerstle, Melanie; Thomas, Anil A.; Danial, Tarek; Chien, Gary] W Los Angeles Vet Affairs Med Ctr, Dept Urol, Los Angeles, CA 90073 USA. [Tsu, Jin-Wen] Kaiser Permanente So Calif, Dept Res & Evaluat, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD NOV PY 2011 VL 25 SU 1 BP A95 EP A95 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 844ZI UT WOS:000296792200292 ER PT J AU Siddiqui, M Prien, EL Dretler, SP Sacco, DE AF Siddiqui, Mohummad Prien, Edwin L. Dretler, Stephen P. Sacco, Dianne E. TI PROSPECTIVE INTERVENTIONAL TRIAL OF CALCIUM CARBONATE SUPPLEMENTS ON HYPEROXALURIA IN STONE FORMERS SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Siddiqui, Mohummad; Prien, Edwin L.; Dretler, Stephen P.; Sacco, Dianne E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD NOV PY 2011 VL 25 SU 1 BP A46 EP A46 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 844ZI UT WOS:000296792200146 ER PT J AU Siddiqui, MM Alvi, K Sharif-Tabrizi, A Dretler, SP Sacco, D AF Siddiqui, Mohummad Minhaj Alvi, Kashif Sharif-Tabrizi, Ahmad Dretler, Stephen P. Sacco, Dianne TI CHANGES IN STONE COMPOSITION IN REPEAT STONE FORMERS SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Siddiqui, Mohummad Minhaj; Alvi, Kashif; Sharif-Tabrizi, Ahmad; Dretler, Stephen P.; Sacco, Dianne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD NOV PY 2011 VL 25 SU 1 BP A48 EP A48 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 844ZI UT WOS:000296792200151 ER PT J AU Yamamoto, H Negro, CLA Gomez-Sancha, F Bachmann, A Choi, BB Tabatabaei, S Malek, RS Woo, H Muir, G AF Yamamoto, Hidekazu Negro, C. L. A. Gomez-Sancha, F. Bachmann, A. Choi, B. B. Tabatabaei, S. Malek, R. S. Woo, H. Muir, G. TI GREENLIGHT HPS LASER PROSTATECTOMY IS SAFE AND GIVES EXCELLENT FUNCTIONAL RESULTS AT MEDIUM-TERM FOLLOW-UP. A PROSPECTIVE INTERNATIONAL MULTICENTRE STUDY SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Yamamoto, Hidekazu; Negro, C. L. A.; Malek, R. S.; Woo, H.; Muir, G.] Kings Coll Hosp, London, England. [Gomez-Sancha, F.] Inst Adv Urol Surg, Madrid, Spain. [Bachmann, A.] Univ Basel Hosp, Dept Urol, CH-4031 Basel, Switzerland. [Choi, B. B.] Weill Cornell Med Ctr, Dept Urol, New York, NY USA. [Tabatabaei, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Malek, R. S.] Westmead Hosp, Dept Urol, Sydney, NSW, Australia. Mayo Clin, Dept Urol, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD NOV PY 2011 VL 25 SU 1 BP A39 EP A39 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 844ZI UT WOS:000296792200123 ER PT J AU Harris, RS Venegas, JG Wongviriyawong, C Winkler, T Kone, M Musch, G Melo, MFV de Prost, N Hamilos, DL Afshar, R Cho, J Luster, AD Medoff, BD AF Harris, R. Scott Venegas, Jose G. Wongviriyawong, Chanikarn Winkler, Tilo Kone, Mamary Musch, Guido Melo, Marcos F. Vidal de Prost, Nicolas Hamilos, Daniel L. Afshar, Roshi Cho, Josalyn Luster, Andrew D. Medoff, Benjamin D. TI F-18-FDG Uptake Rate Is a Biomarker of Eosinophilic Inflammation and Airway Response in Asthma SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE airway constriction; ventilation-perfusion ratio; pulmonary gas exchange; fluorine isotopes; emission-computed tomography; nitrogen isotopes ID POSITRON-EMISSION-TOMOGRAPHY; BRAIN TRANSFER CONSTANTS; ACUTE LUNG INJURY; TIME UPTAKE DATA; GRAPHICAL EVALUATION; VENTILATION DEFECTS; ATOPIC ASTHMA; KINETICS; PET; MEPOLIZUMAB AB In asthma, the relationship among airway inflammation, airway hyperresponsiveness, and lung function is poorly understood. Methods to noninvasively assess these relationships in human subjects are needed. We sought to determine whether F-18-FDG uptake rate (K-i, min(-1)) could serve as a biomarker of eosinophilic inflammation and local lung function. Methods: We used PET/CT to assess regional pulmonary perfusion ((Q) over dot), specific ventilation per unit volume (s(V) over dot(A)), fractional gas content (Fgas), airway wall thickness, and regional K-i 10 h after segmental allergen challenge to the right middle lobe in 6 asthmatic subjects with demonstrated atopy. (Q) over dot, s(V) over dot(A), and Fgas in the allergen-challenged lobe were compared with the right upper lobe, where diluent was applied as a control. The airway wall thickness aspect ratio (omega) of the allergen-challenged airway was compared with those of similarly sized airways from unaffected areas of the lung. Differences in K-i between allergen and diluent segments were compared with those in cell counts obtained 24 h after the allergen challenge by a bronchoalveolar lavage of the respective segments. Results: We found systematic reductions in regional (Q) over dot, s(V) over dot(A), and Fgas and increased v in all subjects. The ratio of eosinophil count (allergen to diluent) was linearly related (R-2 = 0.9917, P < 0.001) to the ratio of K-i. Conclusion: Regional K-i measured with PET is a noninvasive and highly predictive biomarker of eosinophilic airway inflammation and its functional effects. This method may serve to help in the understanding of allergic inflammation and test the therapeutic effectiveness of novel drugs or treatments. C1 [Harris, R. Scott; Kone, Mamary; Hamilos, Daniel L.; Afshar, Roshi; Cho, Josalyn; Luster, Andrew D.; Medoff, Benjamin D.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, Boston, MA 02114 USA. [Harris, R. Scott; Kone, Mamary; Hamilos, Daniel L.; Afshar, Roshi; Cho, Josalyn; Luster, Andrew D.; Medoff, Benjamin D.] Massachusetts Gen Hosp, Allergy & Immunol Unit, Dept Med, Boston, MA 02114 USA. [Harris, R. Scott; Venegas, Jose G.; Wongviriyawong, Chanikarn; Winkler, Tilo; Kone, Mamary; Musch, Guido; Melo, Marcos F. Vidal; de Prost, Nicolas; Hamilos, Daniel L.; Afshar, Roshi; Cho, Josalyn; Luster, Andrew D.; Medoff, Benjamin D.] Harvard Univ, Sch Med, Boston, MA USA. [Venegas, Jose G.; Wongviriyawong, Chanikarn; Winkler, Tilo; Musch, Guido; Melo, Marcos F. Vidal; de Prost, Nicolas] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Harris, RS (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. EM rsharris@mgh.harvard.edu RI Winkler, Tilo/B-5337-2009; OI Winkler, Tilo/0000-0002-7276-5550; de Prost, Nicolas/0000-0002-4833-4320 FU NIH [HL088297, HL07874, AI40618, HL68011, AI095261, HL-04501] FX We thank Mary Loveless and Melissa Bruen for technical assistance with image acquisition and processing; Carol Leary for help with the human studies protocol; Allegra Bruce, Peter Rice, and Ronald Callahan for radiation safety and quality assurance testing of the radioisotopes; and John Correia, William Bucelewicz, and David Lee for preparation of the radioisotopes. This work was supported by grants from the NIH: HL088297, HL07874, AI40618, HL68011, AI095261, and HL-04501. No other potential conflict of interest relevant to this article was reported. NR 29 TC 23 Z9 23 U1 0 U2 2 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 NOV 1 PY 2011 VL 52 IS 11 BP 1713 EP 1720 DI 10.2967/jnumed.110.086355 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 844BJ UT WOS:000296722000015 PM 21990575 ER PT J AU Bona, K Bates, J Wolfe, J AF Bona, Kira Bates, Jennifer Wolfe, Joanne TI Massachusetts' Pediatric Palliative Care Network: Successful Implementation of a Novel State-Funded Pediatric Palliative Care Program SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article AB Background: U.S. children with life-limiting illness face barriers to accessing palliative care. In 2006, Massachusetts signed into law a statute providing for the creation and funding of the Pediatric Palliative Care Network (PPCN). This innovative, exclusively state-funded program provides comprehensive direct and consultative community-based pediatric palliative care services including: (1) pain and symptom management, (2) case management and assessment, (3) social services, counseling, and bereavement services, (4) volunteer support services, (5) respite services, and (6) complementary therapies. Provision of care is through a network of state-licensed hospice programs, and an array of professional and volunteer services. Objective: To describe Massachusetts' experience in implementing a novel pediatric palliative care program. Design: Enrollment and service trends were identified using Massachusetts Department of Public Health administrative data. Responses to a written family satisfaction survey provided to each family enrolled on PPCN are summarized. Results: In fiscal year 2010, PPCN partnered with 11 hospice programs to provide services to 227 children with life-limiting illness. A total of $680,850 (86.7%) of state funding went to direct contract funds for hospices. Admitting diagnoses included cancer (30%), chromosomal abnormalities (17%), neurodegenerative disorders (15%), and other (38%). There were 11 deaths, 100% of which occurred in the family's requested location. Median length of stay on service prior to death was 233 days. Families most commonly implemented psychosocial and case management services, followed by complementary therapies, and volunteer services. Conclusions: Successful implementation of a statewide pediatric palliative care program as modeled in Massachusetts is highly feasible at relatively low cost. C1 [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Ctr Outcomes & Policy Res, Boston, MA 02215 USA. [Bona, Kira; Wolfe, Joanne] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Bona, Kira; Wolfe, Joanne] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Bates, Jennifer] Massachusetts Dept Publ Hlth, Pediat Palliat Care Network, Boston, MA USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Ctr Outcomes & Policy Res, 450 Brookline Ave SM-206, Boston, MA 02215 USA. EM joanne_wolfe@dfci.harvard.edu NR 17 TC 14 Z9 14 U1 1 U2 6 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 NOV PY 2011 VL 14 IS 11 BP 1217 EP 1223 DI 10.1089/jpm.2011.0070 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 843HV UT WOS:000296663800008 PM 21823906 ER PT J AU Higgs, MH Spain, WJ AF Higgs, Matthew H. Spain, William J. TI Kv1 channels control spike threshold dynamics and spike timing in cortical pyramidal neurones SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID AXON INITIAL SEGMENT; ACTION-POTENTIAL INITIATION; HIGH-FREQUENCY OSCILLATIONS; AVIAN COCHLEAR NUCLEUS; COINCIDENCE DETECTION; FAST RIPPLES; IN-VIVO; EPILEPTIC HIPPOCAMPUS; POTASSIUM CHANNELS; AUDITORY NEURONS AB Previous studies showed that cortical pyramidal neurones (PNs) have a dynamic spike threshold that functions as a high-pass filter, enhancing spike timing in response to high-frequency input. While it is commonly assumed that Na(+) channel inactivation is the primary mechanism of threshold accommodation, the possible role of K(+) channel activation in fast threshold changes has not been well characterized. The present study tested the hypothesis that low-voltage activated Kv1 channels affect threshold dynamics in layer 2-3 PNs, using alpha-dendrotoxin (DTX) or 4-aminopyridine (4-AP) to block these conductances. We found that Kv1 blockade reduced the dynamic changes of spike threshold in response to a variety of stimuli, including stimulus-evoked synaptic input, current steps and ramps of varied duration, and noise. Analysis of the responses to noise showed that Kv1 channels increased the coherence of spike output with high-frequency components of the stimulus. A simple model demonstrates that a dynamic spike threshold can account for this effect. Our results show that the Kv1 conductance is a major mechanism that contributes to the dynamic spike threshold and precise spike timing of cortical PNs. C1 [Higgs, Matthew H.; Spain, William J.] Dept Vet Affairs Med Ctr, Neurol Sect, Seattle, WA USA. [Higgs, Matthew H.; Spain, William J.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. [Spain, William J.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. RP Higgs, MH (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Neurol Mail Stop 127,1660 S Columbian Way, Seattle, WA 98108 USA. EM higgsm@uw.edu FU US Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory; Veterans Affairs Merit Review; Veterans Affairs Epilepsy Centre of Excellence FX This material is based on work supported by the US Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory Research Program. Funding was provided by a Veterans Affairs Merit Review to W.J.S. and a Veterans Affairs Epilepsy Centre of Excellence. We thank Robert Foehring and Adrienne Fairhall for helpful discussions, Steve Redman for helpful comments on the manuscript, and Susan Usher for excellent technical assistance. NR 60 TC 41 Z9 42 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV PY 2011 VL 589 IS 21 BP 5125 EP 5142 DI 10.1113/jphysiol.2011.216721 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 839MA UT WOS:000296369000012 PM 21911608 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI The Continuity of Care Checklist: A Critical Frontier in Patient Safety 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. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 2 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 NOV PY 2011 VL 9 IS 11 BP 1217 EP 1218 PG 2 WC Oncology SC Oncology GA 845VR UT WOS:000296853400002 PM 22056653 ER PT J AU Benson, AB Arnoletti, JP Bekaii-Saab, T Chan, E Chen, YJ Choti, MA Cooper, HS Dilawari, RA Engstrom, PF Enzinger, PC Fleshman, JW Fuchs, CS Grem, JL Knol, JA Leong, LA Lin, E May, KS Mulcahy, MF Murphy, K Rohren, E Ryan, DP Saltz, L Sharma, S Shibata, D Skibber, JM Small, W Sofocleous, CT Venook, AP Willett, C AF Benson, Al B., III Arnoletti, J. Pablo Bekaii-Saab, Tanios Chan, Emily Chen, Yi-Jen Choti, Michael A. Cooper, Harry S. Dilawari, Raza A. Engstrom, Paul F. Enzinger, Peter C. Fleshman, James W., Jr. Fuchs, Charles S. Grem, Jean L. Knol, James A. Leong, Lucille A. Lin, Edward May, Kilian Salerno Mulcahy, Mary F. Murphy, Kate Rohren, Eric Ryan, David P. Saltz, Leonard Sharma, Sunil Shibata, David Skibber, John M. Small, William, Jr. Sofocleous, Constantinos T. Venook, Alan P. Willett, Christopher TI Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; colonic neoplasms; colorectal surgery; adjuvant chemotherapy; 5-fluorouracil; adenocarcinoma; neoplasm staging; neoplasm recurrence; irinotecan; oxaliplatin; capecitabine; bevacizumab; cetuximab; panitumumab; metastatic colorectal cancer; neoadjuvant therapy; liver resection ID METASTATIC COLORECTAL-CANCER; III COLON-CANCER; CAPECITABINE PLUS OXALIPLATIN; GROWTH-FACTOR RECEPTOR; RANDOMIZED PHASE-III; HIGH-DOSE LEUCOVORIN; UNRESECTABLE LIVER METASTASES; SURGICAL ADJUVANT BREAST; DISEASE-FREE SURVIVAL; LONG-TERM SURVIVAL C1 [Benson, Al B., III; Mulcahy, Mary F.; Small, William, Jr.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Arnoletti, J. Pablo] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Bekaii-Saab, Tanios] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Chan, Emily] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Choti, Michael A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Cooper, Harry S.; Engstrom, Paul F.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Dilawari, Raza A.] Univ Tennessee, St Jude Childrens Res Hosp, Inst Canc, Knoxville, TN 37996 USA. [Fleshman, James W., Jr.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Fleshman, James W., Jr.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Grem, Jean L.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Knol, James A.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Lin, Edward] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [May, Kilian Salerno] Roswell Pk Canc Inst, Buffalo, NY USA. [Rohren, Eric; Skibber, John M.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Ryan, David P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Saltz, Leonard; Sofocleous, Constantinos T.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Sharma, Sunil] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Shibata, David] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Venook, Alan P.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. RP Benson, AB (reprint author), Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. OI Saltz, Leonard/0000-0001-8353-4670 NR 397 TC 19 Z9 20 U1 2 U2 8 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 NOV PY 2011 VL 9 IS 11 BP 1238 EP 1290 PG 53 WC Oncology SC Oncology GA 845VR UT WOS:000296853400005 PM 22056656 ER PT J AU Wierwille, J Andrews, PM Onozato, ML Jiang, J Cable, A Chen, Y AF Wierwille, Jeremiah Andrews, Peter M. Onozato, Maristela L. Jiang, James Cable, Alex Chen, Yu TI In vivo, label-free, three-dimensional quantitative imaging of kidney microcirculation using Doppler optical coherence tomography SO LABORATORY INVESTIGATION LA English DT Article DE doppler optical coherence tomography (DOCT); glomerular blood flow; kidney microcirculation; optical coherence tomography (OCT) ID RENAL BLOOD-FLOW; SCANNING CONFOCAL MICROSCOPY; POSITRON-EMISSION-TOMOGRAPHY; MULTIPHOTON MICROSCOPY; ANGIOTENSIN-II; DIABETIC-NEPHROPATHY; PERFUSION INDEX; HIGH-SPEED; HEMODYNAMICS; CONTRAST AB Doppler optical coherence tomography (DOCT) is a functional extension of optical coherence tomography (OCT) and is currently being employed in several clinical arenas to quantify blood flow in vivo. In this study, the objective was to investigate the feasibility of DOCT to image kidney microcirculation, specifically, glomerular blood flow. DOCT is able to capture three-dimensional (3D) data sets consisting of a series of cross-sectional images in real time, which enables label-free and non-destructive quantification of glomerular blood flow. The kidneys of adult, male Munich-Wistar rats were exposed through laparotomy procedure after being anesthetized. Following exposure of the kidney beneath the DOCT microscope, glomerular blood flow was observed. The effects of acute mannitol and angiotensin II infusion were also observed. Glomerular blood flow was quantified for the induced physiological states and compared with baseline measurements. Glomerular volume, cumulative Doppler volume, and Doppler flow range parameters were computed from 3D OCT/DOCT data sets. Glomerular size was determined from OCT, and DOCT readily revealed glomerular blood flow. After infusion of mannitol, a significant increase in blood flow was observed and quantified, and following infusion of angiontensin II, a significant decrease in blood flow was observed and quantified. Also, blood flow histograms were produced to illustrate differences in blood flow rate and blood volume among the induced physiological states. We demonstrated 3D DOCT imaging of rat kidney microcirculation in the glomerulus in vivo. Dynamic changes in blood flow were detected under altered physiological conditions demonstrating the real-time imaging capability of DOCT. This method holds promise to allow non-invasive imaging of kidney blood flow for transplant graft evaluation or monitoring of altered-renal hemodynamics related to disease progression. Laboratory Investigation (2011) 91, 1596-1604; doi: 10.1038/labinvest.2011.112; published online 1 August 2011 C1 [Wierwille, Jeremiah; Chen, Yu] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Andrews, Peter M.] Georgetown Univ, Dept Biochem, Washington, DC USA. [Onozato, Maristela L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Jiang, James; Cable, Alex] Thorlabs Inc, Newton, NJ USA. RP Chen, Y (reprint author), Univ Maryland, Fischell Dept Bioengn, 2218 Jeong H Kim Bldg, College Pk, MD 20742 USA. EM yuchen@umd.edu FU State of Maryland; Minta Martin Foundation; Prevent Cancer Foundation; UMB-UMCP SEED; A. Ward Ford Memorial Research Grant; NIH [R21-EB012215] FX This work is supported in part by the Nanobiotechnology Award of the State of Maryland, the Minta Martin Foundation, the Prevent Cancer Foundation, the UMB-UMCP SEED Grant Program, the A. Ward Ford Memorial Research Grant, and NIH R21-EB012215. NR 74 TC 13 Z9 14 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD NOV PY 2011 VL 91 IS 11 BP 1596 EP 1604 DI 10.1038/labinvest.2011.112 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 842MK UT WOS:000296603400005 PM 21808233 ER PT J AU Anttonen, M Farkkila, A Tauriala, H Kauppinen, M MacLaughlin, DT Unkila-Kallio, L Butzow, R Heikinheimo, M AF Anttonen, Mikko Farkkila, Anniina Tauriala, Hanna Kauppinen, Marjut MacLaughlin, David T. Unkila-Kallio, Leila Butzow, Ralf Heikinheimo, Markku TI Anti-Mullerian hormone inhibits growth of AMH type II receptor-positive human ovarian granulosa cell tumor cells by activating apoptosis SO LABORATORY INVESTIGATION LA English DT Article DE ALK; cancer treatment; Mullerian inhibiting substance; ovarian cancer; sex cord stromal tumor; Smad ID CANCER IN-VIVO; PROGNOSTIC-FACTORS; ENHANCED PURIFICATION; INDEPENDENT MECHANISM; SIGNAL-TRANSDUCTION; DUCT REGRESSION; TGF-BETA; SUBSTANCE; EXPRESSION; FOXL2 AB Ovarian granulosa cell tumors (GCTs) are sex cord stromal tumors that constitute 3-5% of all ovarian cancers. GCTs usually present with an indolent course but there is a high risk of recurrence, which associates with increased mortality, and targeted treatments would be desirable. Anti-Mullerian hormone (AMH), a key factor regulating sexual differentiation of the reproductive organs, has been implicated as a growth inhibitor in ovarian cancer. GCTs and normal granulosa cells produce AMH, but its expression in large GCTs is usually downregulated. Further, as the lack of specific AMH-signaling pathway components leads to GCT development in mice, we hypothesized that AMH inhibits growth of GCTs. Utilizing a large panel of human GCT tissue samples, we found that AMH type I receptors (ALK2, ALK3 and ALK6) and type II receptor (AMHRII), as well as their downstream effectors Smad1/5, are expressed and active in GCTs. AMHRII expression was detected in the vast majority (96%) of GCTs and correlated with AMH mRNA and protein expression. AMH mRNA level was low in large GCTs, confirming previous findings on low-AMH protein expression in large human as well as mouse GCTs. To study the functional role of AMH in this peculiar ovarian cancer, we utilized a human GCT cell line (KGN) and 10 primary GCT cell cultures. We found that the AMH-Smad1/5-signaling pathway was active in these cells, and that exogenous AMH further activated Smad1/5 in KGN cells. Furthermore, AMH treatment reduced the number of KGN cells and primary GCT cells, with increasing amounts of AMH leading to augmented activation of caspase-3 and subsequent apoptosis. All in all, these data support the premise that AMH is a growth inhibitor of GCTs. Laboratory Investigation (2011) 91, 1605-1614; doi:10.1038/labinvest.2011.116; published online 1 August 2011 C1 [Anttonen, Mikko; Farkkila, Anniina; Unkila-Kallio, Leila; Butzow, Ralf] Univ Helsinki, Dept Obstet & Gynecol, Helsinki 00029, Finland. [Anttonen, Mikko] Univ Helsinki, Cent Hosp, Biomedicum 2U, Helsinki 00029, Finland. [Anttonen, Mikko; Farkkila, Anniina; Tauriala, Hanna; Kauppinen, Marjut; Heikinheimo, Markku] Univ Helsinki, Childrens Hosp, Pediat Res Ctr, Helsinki 00029, Finland. [Anttonen, Mikko; Farkkila, Anniina; Unkila-Kallio, Leila; Butzow, Ralf; Heikinheimo, Markku] Univ Helsinki, Program Womens Hlth, Helsinki 00029, Finland. [MacLaughlin, David T.] Harvard Univ, Sch Med, Boston, MA USA. [MacLaughlin, David T.] Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. [Butzow, Ralf] Univ Helsinki, Dept Pathol, Helsinki 00029, Finland. [Heikinheimo, Markku] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. RP Anttonen, M (reprint author), Univ Helsinki, Dept Obstet & Gynecol, POB 705, Helsinki 00029, Finland. EM mikko.anttonen@helsinki.fi FU Academy of Finland; National Clinical Graduate School; Helsinki University Central Hospital; Sigrid Juselius Foundation; Finnish Cancer Organizations FX We thank all the gynecologists and operation room staff for supporting the patient recruitment and tissue sample collection for the entire GCT project. We also thank Taru Jokinen and Teija Karkkulainen for excellent assistance, and Dr T Yanase and Dr I Navarro-Teulon for kindly providing the KGN cell line and the AMHRII antibody, respectively. This study was supported by grants from the Academy of Finland (to MA and MH), the National Clinical Graduate School (to AF), Helsinki University Central Hospital Research Funds (to MA, LU-K, RB, and MH), the Sigrid Juselius Foundation (to MH), and Finnish Cancer Organizations (to MH). NR 62 TC 9 Z9 13 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD NOV PY 2011 VL 91 IS 11 BP 1605 EP 1614 DI 10.1038/labinvest.2011.116 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 842MK UT WOS:000296603400006 PM 21808236 ER PT J AU Regan, MM Neven, P Giobbie-Hurder, A Goldhirsch, A Ejlertsen, B Mauriac, L Forbes, JF Smith, I Lang, I Wardley, A Rabaglio, M Price, KN Gelber, RD Coates, AS Thurlimann, B AF Regan, Meredith M. Neven, Patrick Giobbie-Hurder, Anita Goldhirsch, Aron Ejlertsen, Bent Mauriac, Louis Forbes, John F. Smith, Ian Lang, Istvan Wardley, Andrew Rabaglio, Manuela Price, Karen N. Gelber, Richard D. Coates, Alan S. Thuerlimann, Beat CA BIG 1-98 Collaborative Grp IBCSG TI Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8.1 years median follow-up SO LANCET ONCOLOGY LA English DT Article ID ADJUVANT ENDOCRINE THERAPY; COMPARING LETROZOLE; DOUBLE-BLIND; PHASE-III AB Background Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast-cancer recurrence and death. Therefore, trials assessing endocrine therapies for this patient population need extended follow-up. We present an update of efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8.1 years median follow-up. Methods BIG 1-98 is a randomised, phase 3, double-blind trial of postmenopausal women with hormone receptor-positive early breast cancer that compares 5 years of tamoxifen or letrozole monotherapy, or sequential treatment with 2 years of one of these drugs followed by 3 years of the other. Randomisation was done with permuted blocks, and stratified according to the two-arm or four-arm randomisation option, participating institution, and chemotherapy use. Patients, investigators, data managers, and medical reviewers were masked. The primary efficacy endpoint was disease-free survival (events were invasive breast cancer relapse, second primaries [ contralateral breast and non-breast], or death without previous cancer event). Secondary endpoints were overall survival, distant recurrence-free interval (DRFI), and breast cancer-free interval (BCFI). The monotherapy comparison included patients randomly assigned to tamoxifen or letrozole for 5 years. In 2005, after a significant disease-free survival benefit was reported for letrozole as compared with tamoxifen, a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting (IPCW) are used to account for selective crossover to letrozole of patients (n=619) in the tamoxifen arm. Comparison of sequential treatments to letrozole monotherapy included patients enrolled and randomly assigned to letrozole for 5 years, letrozole for 2 years followed by tamoxifen for 3 years, or tamoxifen for 2 years followed by letrozole for 3 years. Treatment has ended for all patients and detailed safety results for adverse events that occurred during the 5 years of treatment have been reported elsewhere. Follow-up is continuing for those enrolled in the four-arm option. BIG 1-98 is registered at clinicaltrials.gov NCT00004205. Findings 8010 patients were included in the trial, with a median follow-up of 8.1 years (range 0-12.4). 2459 were randomly assigned to monotherapy with tamoxifen for 5 years and 2463 to monotherapy with letrozole for 5 years. In the four-arm option of the trial, 1546 were randomly assigned to letrozole for 5 years, 1548 to tamoxifen for 5 years, 1540 to letrozole for 2 years followed by tamoxifen for 3 years, and 1548 to tamoxifen for 2 years followed by letrozole for 3 years. At a median follow-up of 8.7 years from randomisation (range 0-12.4), letrozole monotherapy was significantly better than tamoxifen, whether by IPCW or intention-to-treat analysis (IPCW disease-free survival HR 0.82 [95% CI 0.74-0.92], overall survival HR 0.79 [ 0.69-0.90], DRFI HR 0.79 [ 0.68-0.92], BCFI HR 0.80 [ 0.70-0.92]; intention-to-treat disease-free survival HR 0.86 [ 0.78-0.96], overall survival HR 0.87 [ 0.77-0.999], DRFI HR 0.86 [ 0.74-0.998], BCFI HR 0.86 [ 0.76-0.98]). At a median follow-up of 8.0 years from randomisation (range 0-11.2) for the comparison of the sequential groups with letrozole monotherapy, there were no statistically significant differences in any of the four endpoints for either sequence. 8-year intention-to-treat estimates (each with SE <= 1.1%) for letrozole monotherapy, letrozole followed by tamoxifen, and tamoxifen followed by letrozole were 78.6%, 77.8%, 77.3% for disease-free survival; 87.5%, 87.7%, 85.9% for overall survival; 89.9%, 88.7%, 88.1% for DRFI; and 86.1%, 85.3%, 84.3% for BCFI. Interpretation For postmenopausal women with endocrine-responsive early breast cancer, a reduction in breast cancer recurrence and mortality is obtained by letrozole monotherapy when compared with tamoxifen montherapy. Sequential treatments involving tamoxifen and letrozole do not improve outcome compared with letrozole monotherapy, but might be useful strategies when considering an individual patient's risk of recurrence and treatment tolerability. C1 [Regan, Meredith M.; Giobbie-Hurder, Anita; Price, Karen N.; Gelber, Richard D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Ctr Stat, IBCSG, Boston, MA 02215 USA. [Regan, Meredith M.; Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Neven, Patrick] Catholic Univ Louvain, Univ Hosp Gasthuisberg, Dept Med Oncol, B-3000 Louvain, Belgium. [Goldhirsch, Aron] European Inst Oncol, Milan, Italy. [Goldhirsch, Aron] St Anna Clin, Swiss Ctr Breast Hlth, Lugano, Switzerland. [Ejlertsen, Bent] Rigshosp, Danish Breast Canc Cooperat Grp DBCG, DK-2100 Copenhagen, Denmark. [Mauriac, Louis] Inst Bergonie, Federat Natl Ctr Lutte Canc, Bordeaux, France. [Forbes, John F.] Univ Newcastle, Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW 2300, Australia. [Smith, Ian] Royal Marsden Hosp, London SW3 6JJ, England. [Smith, Ian] Royal Marsden NHS Trust, Surrey, England. [Lang, Istvan] Natl Inst Oncol, Budapest, Hungary. [Wardley, Andrew] S Manchester Univ Hosp Trust, Christie Hosp NHS Trust, Manchester, Lancs, England. [Rabaglio, Manuela] IBCSG Coordinating Ctr, Bern, Switzerland. [Rabaglio, Manuela] Univ Bern, Inselspital, CH-3010 Bern, Switzerland. [Price, Karen N.; Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Coates, Alan S.] Int Breast Canc Study Grp, Sydney, NSW, Australia. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Thuerlimann, Beat] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Thuerlimann, Beat] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. RP Regan, MM (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Ctr Stat, IBCSG, Mailstop CLS11007,450 Brookline Ave, Boston, MA 02215 USA. EM mregan@jimmy.harvard.edu RI Munzone, Elisabetta/G-8848-2011; friedlander, michael/G-3490-2013; Cheuk, Robyn/H-1944-2013; GLADIEFF, Laurence/O-5129-2014; Wardley, ANdrew/N-8135-2015; Gonzalez Larriba, Jose Luis/G-6177-2016; Petruzelka, Lubos/A-2750-2017; Rimassa, Lorenza/N-4884-2016; Sedlackova, Eva/B-9959-2017; Wyld, David/B-8893-2015; Procopio, Giuseppe/K-2072-2016 OI friedlander, michael/0000-0002-6488-0604; Cheuk, Robyn/0000-0001-9516-5526; GLADIEFF, Laurence/0000-0002-6980-9719; Wardley, ANdrew/0000-0002-9639-0888; Gonzalez Larriba, Jose Luis/0000-0003-2631-0309; Petruzelka, Lubos/0000-0002-4397-0635; Rimassa, Lorenza/0000-0001-9957-3615; Sedlackova, Eva/0000-0002-0089-1611; Wyld, David/0000-0001-9523-4333; Procopio, Giuseppe/0000-0002-2498-402X FU Novartis; United States National Cancer Institute; International Breast Cancer Study Group; Roche; Takeda; Swedish Cancer Society; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); United States National Cancer Institute [CA-75362]; Cancer Research Switzerland/Oncosuisse; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK) FX Funding Novartis, United States National Cancer Institute, International Breast Cancer Study Group.; AW had a consultant or advisory role for Novartis and BE had a consultant or advisory role for Pfizer. BT own stocks for Novartis. JFF has received honoraria from AstraZeneca; AW has received honoraria from Novartis. AG has received honoraria from Novartis and Pfizer. BT has received honoraria from AstraZeneca, Novartis. RDG has received research funding from Novartis; BE has received research funding from Novartis. AC has received travel grants from Roche and Takeda. All other authors declared no conflicts of interest.; The BIG 1-98 trial was financed by Novartis and coordinated by International Breast Cancer Study Group (IBCSG). Other support for the IBCSG was provided by: Swedish Cancer Society, The Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group, Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research (SAKK), United States National Cancer Institute Grant CA-75362, Cancer Research Switzerland/Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). NR 23 TC 137 Z9 143 U1 3 U2 34 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 NOV PY 2011 VL 12 IS 12 BP 1101 EP 1108 DI 10.1016/S1470-2045(11)70270-4 PG 8 WC Oncology SC Oncology GA 842GC UT WOS:000296581400019 PM 22018631 ER PT J AU Mar, BG Amakye, D Aifantis, I Buonamici, S AF Mar, B. G. Amakye, D. Aifantis, I. Buonamici, S. TI The controversial role of the Hedgehog pathway in normal and malignant hematopoiesis SO LEUKEMIA LA English DT Review DE Hedgehog pathway; hematopoietic stem cells; Smoothened inhibitors; chronic myeloid leukemia ID CHRONIC MYELOID-LEUKEMIA; BASAL-CELL CARCINOMA; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOCYTIC-LEUKEMIA; PATIENTS RECEIVING IMATINIB; CANCER STEM-CELLS; MURINE YOLK-SAC; SONIC HEDGEHOG; BCR-ABL; SIGNALING PATHWAY AB Hedgehog (Hh) is a developmental signaling pathway in which Hh ligands bind Patched (Ptch), which relieves its inhibition of Smoothened (Smo), allowing the Gli family of transcription factors to translocate to the nucleus and activate Hh target genes. The role of Hh signaling in hematopoiesis is controversial and ill defined. Although some groups observed self-renewal defects with decreased replating and reduced efficiency of secondary murine transplants, other groups reported no hematopoietic phenotypes, which may be related to the timing of Hh abrogation. In malignant hematopoiesis, most attention has been focused on the role of Hh signaling in chronic myeloid leukemia (CML), considered by many to be a stem cell disorder that bears the constitutively active BCR-ABL tyrosine kinase. Despite the elimination of most leukemia cells through BCR-ABL inhibition, most patients remain PCR positive, suggesting that the putative CML stem cell may be resistant to kinase antagonism. Groups are now exploring the Hh pathway as an alternate pathway supporting CML stem cell survival. Knockdown or inhibition of Smo abrogates or delays the appearance of CML in several in vitro and in vivo models. These data have lead to clinical trials using BCR-ABL kinase and novel Smo inhibitors in combination. Leukemia (2011) 25, 1665-1673; doi:10.1038/leu.2011.143; published online 10 June 2011 C1 [Amakye, D.; Buonamici, S.] Novartis Inst Biomed Res, Dept Oncol, Cambridge, MA 02139 USA. [Mar, B. G.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Aifantis, I.] NYU, Sch Med, Howard Hughes Med Inst, New York, NY USA. [Aifantis, I.] NYU, Sch Med, Dept Pathol, New York, NY USA. [Aifantis, I.] NYU, Sch Med, Helen & Martin S Kimmel Stem Cell Ctr, New York, NY USA. RP Buonamici, S (reprint author), Novartis Inst Biomed Res, Dept Oncol, 250 Massachusetts Ave, Cambridge, MA 02139 USA. EM silvia.buonamici@novartis.com OI Mar, Brenton/0000-0002-3857-9324 FU National Institutes of Health [RO1CA133379, RO1CA105129, R21CA141399, RO1CA149655]; Leukemia & Lymphoma Society; American Cancer Society [RSG0806801] FX We thank the Smoothened team and Yao Yung-mae at Novartis for stimulating discussions and critical reading of the manuscript. IA is supported by the National Institutes of Health (RO1CA133379, RO1CA105129, R21CA141399 and RO1CA149655 to IA), the Leukemia & Lymphoma Society and the American Cancer Society (RSG0806801 to IA). IA is a Howard Hughes Medical Institute Early Career Scientist. NR 96 TC 33 Z9 33 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 2011 VL 25 IS 11 BP 1665 EP 1673 DI 10.1038/leu.2011.143 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 846RY UT WOS:000296922100001 PM 21660044 ER PT J AU Tranah, GJ Manini, TM Lohman, KK Nalls, MA Kritchevsky, S Newman, AB Harris, TB Miljkovic, I Biffi, A Cummings, SR Liu, YM AF Tranah, Gregory J. Manini, Todd M. Lohman, Kurt K. Nalls, Michael A. Kritchevsky, Stephen Newman, Anne B. Harris, Tamara B. Miljkovic, Iva Biffi, Alessandro Cummings, Steven R. Liu, Yongmei TI Mitochondrial DNA variation in human metabolic rate and energy expenditure SO MITOCHONDRION LA English DT Article DE Metabolic rate; Energetics; Mitochondria; Mitochondrial haplogroups; mtDNA; Oxidative phosphorylation ID DOUBLY-LABELED WATER; CYTOCHROME-C-OXIDASE; PHYSICAL-ACTIVITY; DROSOPHILA-MELANOGASTER; ADAPTIVE SELECTION; HUMAN MTDNA; SPERM MOTILITY; LONGEVITY; EPISTASIS; EVOLUTION AB The role of climate in driving selection of mtDNA as Homo sapiens migrated out of Africa into Eurasia remains controversial. We evaluated the role of mtDNA variation in resting metabolic rate (RMR) and total energy expenditure (TEE) among 294 older, community-dwelling African and European American adults from the Health, Aging and Body Composition Study. Common African haplogroups L0, L2 and L3 had significantly lower RMRs than European haplogroups H, JT and UK with haplogroup L1 RMR being intermediate to these groups. This study links mitochondrial haplogroups with ancestry-associated differences in metabolic rate and energy expenditure. (C) 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved. C1 [Tranah, Gregory J.] UCSF, Calif Pacific Med Ctr Res Inst, San Francisco Coordinating Ctr, San Francisco, CA 94107 USA. [Manini, Todd M.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL 32601 USA. [Lohman, Kurt K.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA. [Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Kritchevsky, Stephen; Liu, Yongmei] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC 27157 USA. [Newman, Anne B.; Miljkovic, Iva] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Biffi, Alessandro] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Biffi, Alessandro] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Biffi, Alessandro] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. RP Tranah, GJ (reprint author), UCSF, Calif Pacific Med Ctr Res Inst, San Francisco Coordinating Ctr, 185 Berry St,Lobby 4,Suite 5700, San Francisco, CA 94107 USA. EM gtranah@sfcc-cpmc.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Miljkovic, Iva/0000-0002-3155-9777; Kritchevsky, Stephen/0000-0003-3336-6781 FU NIH, National Institute on Aging; NIA [N01AG62101, N01AG62103, N01AG62106, 1R03AG032498-01, 1R01AG032098-01A1]; National Institutes of Health [HHSN268200782096C] FX This research is supported in part by the Intramural Research Program of the NIH, National Institute on Aging. This research was supported by NIA contracts N01AG62101, N01AG62103, N01AG62106 and NIA grant 1R03AG032498-01. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. NR 66 TC 13 Z9 13 U1 1 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD NOV PY 2011 VL 11 IS 6 BP 855 EP 861 DI 10.1016/j.mito.2011.04.005 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 846ZI UT WOS:000296941300003 PM 21586348 ER PT J AU Hideshima, T Richardson, PG Anderson, KC AF Hideshima, Teru Richardson, Paul G. Anderson, Kenneth C. TI Mechanism of Action of Proteasome Inhibitors and Deacetylase Inhibitors and the Biological Basis of Synergy in Multiple Myeloma SO MOLECULAR CANCER THERAPEUTICS LA English DT Review ID NF-KAPPA-B; UNFOLDED PROTEIN RESPONSE; ENDOTHELIAL GROWTH-FACTOR; PANOBINOSTAT LBH589; PLUS DEXAMETHASONE; MOLECULAR SEQUELAE; MURINE MODEL; CELL-GROWTH; PHASE-I; BORTEZOMIB AB Novel agents, including the proteasome inhibitor bortezomib, have significantly improved the response and survival of patients with multiple myeloma over the last decade. Despite these advances, many patients relapse or do not benefit from the currently available therapies; thus, multiple myeloma remains an incurable disease. Deacetylase inhibitors (DACi), including panobinostat and vorinostat, have recently emerged as novel agents being evaluated in the treatment of multiple myeloma. Deacetylases are a group of enzymes with effects on various intracellular proteins, including histones, transcription factors, and molecular chaperones. Although DACi inhibit cell growth and induce apoptosis in multiple myeloma cells as a single agent, synergistic activity has been observed when they were used in combination with bortezomib. The mechanistic basis of synergy is multifactorial and includes disruption of protein degradation and inhibition of the interaction of multiple myeloma cells with the tumor microenvironment. This review summarizes recent advancements in the understanding of the mechanism of action of proteasome inhibitors and DACi in multiple myeloma and examines the biological basis of their synergistic effects. Data from the studies summarized here have been used as the rationale for the implementation of phase II and III clinical trials of DACi, alone and combined with bortezomib, in relapsed and refractory multiple myeloma. Mol Cancer Ther; 10(11); 2034-42. (C) 2011 AACR. C1 [Hideshima, Teru] Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hideshima, T (reprint author), Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM teru_hideshima@dfci.harvard.edu FU NIH SPORE [IP50 CA-10070, PO-1 78378, RO-1 CA-50947]; LeBow Family Fund to Cure Myeloma; American Cancer Society FX This study is supported by NIH SPORE IP50 CA-10070, PO-1 78378, and RO-1 CA-50947 grants; the LeBow Family Fund to Cure Myeloma (K.C. Anderson); and American Cancer Society Clinical Reward Professorship (K.C. Anderson). Financial support for editorial assistance was provided by Novartis. NR 52 TC 106 Z9 109 U1 0 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD NOV PY 2011 VL 10 IS 11 BP 2034 EP 2042 DI 10.1158/1535-7163.MCT-11-0433 PG 9 WC Oncology SC Oncology GA 844ZA UT WOS:000296791300018 PM 22072815 ER PT J AU Underhill, ML Dickerson, SS AF Underhill, Meghan L. Dickerson, Suzanne S. TI Engaging in Medical Vigilance: Understanding the Personal Meaning of Breast Surveillance SO ONCOLOGY NURSING FORUM LA English DT Article ID FAMILY-HISTORY; PSYCHOLOGICAL IMPACT; YOUNGER WOMEN; HIGH-RISK; GENETIC PREDISPOSITION; HEREDITARY BREAST; SCREENING-PROGRAM; OVARIAN-CANCER; MRI; MAMMOGRAPHY AB Purpose/Objectives: To explore how women with a hereditary risk of breast cancer experience living with and managing that risk through surveillance. Research Approach: Hermeneutic phenomenology guided the qualitative research design. Setting: The Facing Our Risk of Cancer Empowered online organization. Participants: 9 women undergoing breast surveillance for hereditary breast cancer risk recruited through purposive sampling. Methodologic Approach: Data were collected through semistructured interviews lasting about an hour. A team approach guided data analysis of transcribed interview text based on a modified Diekelman, Allen, and Tanner method. Main Research Variables: Lived experience and personal meaning of hereditary breast cancer risk and surveillance. Findings: Hereditary risk of breast cancer involves a change in one's view of life and necessitates engaging in medical vigilance, often making these women feel ill when they are otherwise healthy. Most have personal family experiences of cancer and value surveillance, although they live with the "what if" of a cancer diagnosis when waiting for surveillance results. All women discussed a need for accurate information, support, and guidance from healthcare providers. Conclusions: Women became their own experts at living with and managing hereditary breast cancer risk. Experiences and interactions within the healthcare system influenced the meaning of breast surveillance. Interpretation: Nurses should be aware of the high level of knowledge among women living with hereditary risk and respect their knowledge by providing accurate and informed care. That can occur only through proper education of nurses and all healthcare professionals working with women at risk for hereditary breast cancer so that they understand current standards of care and how hereditary breast cancer risk-is defined and managed. C1 [Underhill, Meghan L.] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. [Underhill, Meghan L.] Univ Massachusetts, Sch Nursing, Boston, MA 02125 USA. [Dickerson, Suzanne S.] SUNY Buffalo, Sch Nursing, Buffalo, NY 14260 USA. RP Underhill, ML (reprint author), Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. EM meghanl_underhill@dfci.harvard.edu NR 33 TC 4 Z9 4 U1 0 U2 5 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 NOV PY 2011 VL 38 IS 6 BP 686 EP 694 DI 10.1188/11.ONF.686-694 PG 9 WC Oncology; Nursing SC Oncology; Nursing GA 846WE UT WOS:000296933100010 PM 22037331 ER PT J AU Koyfman, A Brem, E Chiang, VW AF Koyfman, Alex Brem, Elizabeth Chiang, Vincent W. TI Thrombotic Thrombocytopenic Purpura SO PEDIATRIC EMERGENCY CARE LA English DT Review DE thrombotic thrombocytopenic purpura; fever; anemia; thrombocytopenia; renal abnormalities; neurologic abnormalities ID HEMOLYTIC-UREMIC SYNDROME; VON-WILLEBRAND-FACTOR; FACTOR-CLEAVING PROTEASE; PLASMA-EXCHANGE; CLINICAL-OUTCOMES; ADAMTS13 ACTIVITY; CYCLOSPORINE; RITUXIMAB; ADOLESCENTS; CHILDHOOD AB In 1924, Dr Eli Moschcowitz described a 16-year-old adolescent girl with abrupt onset of petechiae, hemolytic anemia, followed by paralysis, coma, and death. Autopsy showed widespread hyaline thrombi in the terminal arterioles and capillaries of various organs. The syndrome described by Moschowitz is now known as thrombotic thrombocytopenic purpura. C1 [Koyfman, Alex] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Koyfman, Alex] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brem, Elizabeth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Chiang, Vincent W.] Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. RP Koyfman, A (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St,Neville House, Boston, MA 02115 USA. EM akoyfman@partners.org NR 27 TC 1 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-5161 J9 PEDIATR EMERG CARE JI Pediatr. Emerg. Care PD NOV PY 2011 VL 27 IS 11 BP 1085 EP 1091 DI 10.1097/PEC.0b013e318236068c PG 7 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA 844RB UT WOS:000296763900020 PM 22068077 ER PT J AU Johnson, CV Mimiaga, MJ Reisner, SL VanDerwarker, R Mayer, KH AF Johnson, Carey V. Mimiaga, Matthew J. Reisner, Sari L. VanDerwarker, Rodney Mayer, Kenneth H. TI Barriers and Facilitators to Routine HIV Testing: Perceptions from Massachusetts Community Health Center Personnel SO AIDS PATIENT CARE AND STDS LA English DT Article ID FOR-DISEASE-CONTROL; UNITED-STATES; REVISED RECOMMENDATIONS; CARE SETTINGS; PREVALENCE; WOMEN; ADOLESCENTS; KNOWLEDGE; ADULTS AB Since 2006, the Centers for Disease Control and Prevention (CDC) has recommended routine, voluntary HIV testing for persons aged 13-64 in all health care settings, including the elimination of separate informed consent, which remains in effect in five states including Massachusetts. Community health centers (CHCs) represent an important HIV testing site for at-risk populations. From April to December 2008 a qualitative interview was administered to one senior personnel from each of 30 CHCs in Massachusetts, to identify barriers and facilitators to implementing CDC recommendations and to elucidate strategies to improve routine HIV testing. The following themes emerged as routine HIV testing barriers: (1) provider time constraints, including time to administer counseling and separate informed consent; (2) lack of funding, staff, and space; (3) provider, patient, and community discomfort; (4) inconsistent levels of awareness regarding CDC recommendations; and (5) perceived incompatibility with Massachusetts HIV testing policy. Facilitators included designation of personnel to serve as organizational "champions" for routine testing and use of clinical reminders within electronic medical records to prompt HIV testing. Strategies identified to improve routine HIV testing rates among Massachusetts CHCs included more explicit state-level guidelines; organizational buy-in; collaborative analysis to integrate testing within existing activities; and provider, patient and community education. C1 [Johnson, Carey V.; Mimiaga, Matthew J.; Reisner, Sari L.; VanDerwarker, Rodney; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Reisner, Sari L.] Harvard Univ, Sch Med, Dept Soc Human Dev & Hlth, Boston, MA USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Mimiaga, MJ (reprint author), MGH Harvard Behav Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM mmimiaga@partners.org FU Gilead Science, Inc. [2691] FX This project was supported by a Testing and Linkage to Care grant (#2691) from Gilead Science, Inc. awarded to Drs. Mayer and Mimiaga, who exercised full control over the project. The content is solely the responsibility of the authors and does not necessarily represent the official view of Gilead Science, Inc. NR 35 TC 10 Z9 10 U1 1 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD NOV PY 2011 VL 25 IS 11 BP 647 EP 655 DI 10.1089/apc.2011.0180 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 842FD UT WOS:000296577100004 PM 22023315 ER PT J AU Schacht, JP Randall, PK Waid, LR Baros, AM Latham, PK Wright, TM Myrick, H Anton, RF AF Schacht, Joseph P. Randall, Patrick K. Waid, L. R. Baros, Alicia M. Latham, Patricia K. Wright, Tara M. Myrick, Hugh Anton, Raymond F. TI Neurocognitive Performance, Alcohol Withdrawal, and Effects of a Combination of Flumazenil and Gabapentin in Alcohol Dependence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcoholism; Anticonvulsant; gamma-Aminobutyric Acid; Neurocognitive; Withdrawal ID ETHANOL WITHDRAWAL; GABA(A) RECEPTORS; SUBSTANCE-ABUSE; MULTIPLE DETOXIFICATIONS; COGNITIVE IMPAIRMENT; HEALTHY-VOLUNTEERS; GENE-EXPRESSION; OUTCOMES; CARBAMAZEPINE; INTERFERENCE AB Background: Among some alcohol-dependent individuals, early alcohol abstinence is marked by alcohol withdrawal (AW), a phenomenon mediated by GABA and glutamate signaling. We previously reported that a combination of 2 medications that affect GABA and glutamate tone, gabapentin and flumazenil, more effectively reduced drinking among individuals with higher pretreatment AW (Anton et al., 2009). This study evaluated whether this finding is related to changes in neurocognitive performance, which is also affected by cortical GABA and glutamate tone. Methods: Neurocognitive performance was assessed at baseline and twice during the first week of treatment among 60 alcohol-dependent participants in the previously published clinical trial. Results: AW was associated with poorer baseline performance on 4 of 8 measures, and individuals with higher baseline AW who received the gabapentin and flumazenil combination demonstrated greater improvement on a measure of response inhibition than those with lower AW or those who received a combination of placebos. Improvement in response inhibition during the first week and medication group interacted in their effect on subsequent drinking, such that improvement predicted greater abstinence only among individuals who received gabapentin and flumazenil. Improvement on other neurocognitive measures was neither differentially impacted by medication or baseline AW nor related to subsequent drinking. Conclusions: Taken together, these data suggest that acute AW accounts for a small proportion of variance in neurocognitive performance, that gabapentin and flumazenil slightly improve response inhibition during early abstinence, and that such improvement may somewhat reduce later drinking. However, these medications may not affect other neurocognitive domains. C1 [Schacht, Joseph P.; Randall, Patrick K.; Waid, L. R.; Baros, Alicia M.; Latham, Patricia K.; Wright, Tara M.; Myrick, Hugh; Anton, Raymond F.] Med Univ S Carolina, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. [Wright, Tara M.; Myrick, Hugh] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Schacht, JP (reprint author), Med Univ S Carolina, Ctr Drug & Alcohol Programs, 67 President St,MSC 861, Charleston, SC 29425 USA. EM schacht@musc.edu FU Hythiam, Inc.; National Institute on Alcohol Abuse and Alcoholism [T32 AA007474, K05 AA017435] FX This work was conducted under an unrestricted grant from Hythiam, Inc. JPS was supported by an institutional training grant (T32 AA007474) and RFA by a senior scientist research and mentorship award (K05 AA017435) from the National Institute on Alcohol Abuse and Alcoholism. NR 68 TC 5 Z9 5 U1 6 U2 11 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 NOV PY 2011 VL 35 IS 11 BP 2030 EP 2038 DI 10.1111/j.1530-0277.2011.01554.x PG 9 WC Substance Abuse SC Substance Abuse GA 841SG UT WOS:000296532800014 PM 21631542 ER PT J AU Schlansky, B Sonnenberg, A AF Schlansky, Barry Sonnenberg, Amnon TI Epidemiology of Noncardia Gastric Adenocarcinoma in the United States SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HELICOBACTER-PYLORI INFECTION; STOMACH-CANCER MORTALITY; US ADULTS; CARDIA; TRENDS; ESOPHAGEAL; PREVENTION; BURDEN; RISK AB OBJECTIVES: Adenocarcinomas of the cardia (International Classification of Diseases (ICD)-9 code 151.0) and stomach (ICD-9 codes 151.1-151.9) are frequently grouped together in epidemiologic statistics, but are clearly distinct diseases. The objective of this study was to describe the current epidemiology of noncardia gastric cancer (noncardia gastric adenocarcinoma (NCGA)) in the United States. METHODS: Rates of NCGA in the United States from 1997 to 2008 were analyzed in three national databases: the Surveillance, Epidemiology, and End Results registry was used for incidence, the Healthcare Costs and Utilization Project for hospitalizations, and the Compressed Mortality File for mortality. Population-based rates were calculated and age-adjusted to the US 2000 population using direct standardization. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated and adjusted for confounders with the Mantel-Haenszel method. RESULTS: Annually, NCGA was associated with 18,873 incident cases, 17,284 hospitalizations for principal discharge diagnoses, 31,354 hospitalizations for all-listed diagnoses, and 11,562 deaths. Incidence was greater in men (OR = 1.56, CI = 1.53-1.59) and non-White races (OR = 2.38, 2.33-2.43). Hospitalization was more common in men (1.82, 1.81-1.83) and non-White races (2.13, 2.10-2.15). Mortality was more common in men (1.83, 1.81-1.86) and non-White races (2.23, 2.20-2.26). NCGA rates showed a marked age-dependent rise (P < 0.001). Hospitalization and mortality were greatest in the Northeast region of the United States (P < 0.001). CONCLUSIONS: Epidemiologic patterns of NCGA were congruent in three national databases. Older age, male gender, non-White race, and residence in the Northeast region were associated with increased risk. These patterns may reflect the underlying variations in Helicobacter pylori, lifestyle, and environmental exposures. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Schlansky, Barry; Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Dept Med, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US,Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 39 TC 28 Z9 30 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2011 VL 106 IS 11 BP 1978 EP 1985 DI 10.1038/ajg.2011.213 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 844ZD UT WOS:000296791700014 PM 22008896 ER PT J AU Ananthakrishnan, AN Hur, C Juillerat, P Korzenik, JR AF Ananthakrishnan, Ashwin N. Hur, Chin Juillerat, Pascal Korzenik, Joshua R. TI Strategies for the Prevention of Postoperative Recurrence in Crohn's Disease: Results of a Decision Analysis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID SCHEDULED MAINTENANCE TREATMENT; COST-EFFECTIVENESS; CONTROLLED-TRIAL; ILEAL RESECTION; MARKOV MODEL; RISK-FACTORS; DOUBLE-BLIND; INFLIXIMAB; SURGERY; AZATHIOPRINE AB OBJECTIVES: Nearly 70% of patients with Crohn's disease (CD) undergo surgical resection, with one-quarter subsequently developing clinical recurrence within 12 months. Several options exist for the prevention of postoperative recurrence in CD, but the comparative cost effectiveness of these competing strategies has not been previously analyzed. METHODS: We developed a decision analytic model comprising five strategies-No Treatment, azathioprine (AZA), antibiotics(ABX), upfront infliximab(IFX), and tailored IFX that consisted of no upfront therapy with initiation of IFX in patients with severe endoscopic recurrence at 6 months. The base-case 1-year clinical recurrence rate was 24% with reduction in recurrence by 41%, 77%, and 99% for AZA, ABX, and IFX, respectively. A 1-year time horizon was used and sensitivity analyses were performed. RESULTS: At the base-case analysis, the ABX (0.82 quality-adjusted life years (QALYs)) and AZA (0.81 QALYs) arms were more effective and less expensive than the No Treatment strategy (0.80 QALYs). The most effective strategy was upfront IFX (0.83 QALYs); however, this was also the most expensive and resulted in a high incremental cost-effectiveness ratio (ICER) ($777,732/QALY) compared with no treatment. The tailored IFX arm was less effective than upfront use but had a more acceptable ICER. On increasing the recurrence rate to 78% (high-risk patients), upfront IFX resulted in 0.07 QALYs (ICER $130,580/QALY) gained compared with No Treatment, whereas ABX, AZA, and tailored IFX arms dominated No Treatment. CONCLUSION: Antibiotics are the most cost-effective option for preventing postoperative recurrence, but they have been associated with high rates of intolerance precluding widespread use. Upfront IFX is the most efficacious strategy but is not cost effective even in high-risk patients. Reserving IFX use for high-risk patients with early endoscopic recurrence is more cost effective than upfront use in all patients. C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Gastrointestinal Unit, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.; Hur, Chin; Korzenik, Joshua R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Gastrointestinal Unit, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org OI Hur, Chin/0000-0002-2819-7576 FU Procter and Gamble; Warner Chilcott FX Dr Korzenik has been a consultant for Procter and Gamble, Shire Pharmaceuticals, and CytokinePharma, and receives research support from Procter and Gamble and Warner Chilcott. Drs Ananthakrishnan, Hur, and Juillerat have no financial disclosures. NR 35 TC 19 Z9 19 U1 1 U2 8 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 NOV PY 2011 VL 106 IS 11 BP 2009 EP 2017 DI 10.1038/ajg.2011.237 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 844ZD UT WOS:000296791700018 PM 21788991 ER PT J AU Leung, AA Wright, A Pazo, V Karson, A Bates, DW AF Leung, Alexander A. Wright, Adam Pazo, Valeria Karson, Andrew Bates, David W. TI Risk of Thiazide-induced Hyponatremia in Patients with Hypertension SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Hypertension; Hyponatremia; Incidence; Thiazide diuretics ID CALCIUM-CHANNEL BLOCKER; PROSPECTIVELY-DESIGNED OVERVIEWS; MAJOR CARDIOVASCULAR EVENTS; BLOOD-PRESSURE; RANDOMIZED-TRIALS; HOSPITALIZED-PATIENTS; LOWERING TREATMENT; MILD HYPONATREMIA; DIURETICS; OUTCOMES AB BACKGROUND: Although hyponatremia is a well-recognized complication of treatment with thiazide diuretics, the risk of thiazide-induced hyponatremia remains uncertain in routine care. METHODS: We conducted a retrospective cohort study using a multicenter clinical research registry to identify 2613 adult outpatients that were newly treated for hypertension between January 1, 2000 and December 31, 2005 at 2 teaching hospitals in Boston, Massachusetts, and followed them for up to 10 years. RESULTS: Two hundred twenty patients exposed to ongoing thiazide therapy were compared with 2393 patients who were not exposed. In the exposed group, 66 (30%) developed hyponatremia (sodium <= 130 mmol/L). The adjusted incidence rate of hyponatremia was 140 cases per 1000 person-years for patients treated with thiazides, compared with 87 cases per 1000 person-years in those without thiazides. Patients exposed to thiazides were more likely to develop hyponatremia (adjusted incidence rate ratio, 1.61; 95% confidence interval [CI], 1.15-2.25). There was no significant difference in the risk of hospitalizations associated with hyponatremia (adjusted rate ratio, 1.04; 95% CI, 0.46-2.32) or mortality (adjusted rate ratio, 0.41; 95% CI, 0.12-1.42). The number needed to harm (to result in one excess case of incident hyponatremia in 5 years) was 15.02 (95% CI, 7.88-160.30). CONCLUSIONS: Approximately 3 in 10 patients exposed to thiazides who continue to take them develop hyponatremia. (C) 2011 Elsevier Inc. All rights reserved. . The American Journal of Medicine (2011) 124, 1064-1072 C1 [Leung, Alexander A.; Wright, Adam; Pazo, Valeria; Bates, David W.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, Boston, MA 02120 USA. [Karson, Andrew] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RP Bates, DW (reprint author), Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM dbates@partners.org NR 43 TC 28 Z9 30 U1 0 U2 4 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 NOV PY 2011 VL 124 IS 11 BP 1064 EP 1072 DI 10.1016/j.amjmed.2011.06.031 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 842EW UT WOS:000296576200024 PM 22017784 ER PT J AU Gerlock, AA Grimesey, JL Pisciotta, AK Harel, O AF Gerlock, April A. Grimesey, Jackie L. Pisciotta, Alisa K. Harel, Ofer TI Documentation of Screening for Perpetration of Intimate Partner Violence in Male Veterans with PTSD SO AMERICAN JOURNAL OF NURSING LA English DT Article DE documentation; intimate partner violence; partner abuse; perpetrators; posttraumatic stress disorder; screening; veterans ID DOMESTIC VIOLENCE; ABUSED WOMEN; HEALTH; FAMILY; CARE; SETTINGS; GUIDELINES; BEHAVIORS; SUICIDE; SYSTEM AB Background: Men seeking care for posttraumatic stress disorder (PTSD) are believed to have high rates of relationship conflict and intimate partner violence (IPV). But little is known about screening for IPV perpetration in this population. Objective: In phase one of a two-phase study of male veterans treated for PTSD, the primary objective was to determine how many veterans' records showed documentation that they'd been screened for IPV perpetration. The secondary objective was to count the total number of screenings and to determine whether an initial screening affected future screenings. Methods: For this retrospective cohort study, a stratified random sample of 10% (N = 507) of all male veterans receiving treatment for PTSD at a U.S. Department of Veterans Affairs health care facility in a five-year period (November 2002 to November 2007) was selected and more than 70,000 progress notes were reviewed. The presence or absence of a documented screening for IPV perpetration in each record was noted and a Spearman rank correlation test to determine the relationship between the documentation of a first screening and future screenings was performed. Results: Of the 507 records examined, 120 (24%) showed documentation of screening for IPV perpetration. Of those, 73 (61%) showed positive results for IPV perpetration, and 61 (51%) showed more than one screening. Documentation of screening was most likely to have occurred at the veteran's initial appointment (71%) and in an outpatient mental health setting (72%); IPV perpetration was determined most often as the result of a provider's inquiry (45%). There was a total of 415 screenings, including 356 in records in which there was more than one screening. The documentation of a single screening for IPV perpetration was significantly correlated with the documentation of subsequent screenings and with IPV perpetration determination (Spearman rank correlation = 0.611, P < 0.001). Also, veterans with documented IPV perpetration and high rates of relationship conflict accessed the health care system twice as often as those without such documentation. Conclusions: In the sample analyzed, fewer than a quarter of male veterans with PTSD had a documented screening for IPV perpetration. Also, because those identified as IPV perpetrators accessed the health care system at a higher rate than those not so identified and repeated screenings were associated with a higher rate of IPV perpetrator determinations, health care providers should be made more aware of opportunities for screening for IPV in this population. C1 [Gerlock, April A.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Grimesey, Jackie L.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Tacoma, WA USA. [Harel, Ofer] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP Gerlock, AA (reprint author), Univ Washington, Sch Nursing, Seattle, WA 98195 USA. EM april.gerlock@va.gov RI Schueter, nicos/A-3625-2014 FU Office of Research and Development, Nursing Research Initiative, Department of Veterans Affairs [NRI 04-040]; University of Connecticut FX This material is based upon the work supported by the Office of Research and Development, Nursing Research Initiative (NRI 04-040), Department of Veterans Affairs, and by the University of Connecticut. The authors acknowledge Anne Ganley, Jeff Edleson, and Patricia Betrus for their assistance in project design and manuscript development; they received a consultation fee from the grant. NR 37 TC 4 Z9 4 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD NOV PY 2011 VL 111 IS 11 BP 26 EP 32 DI 10.1097/01.NAJ.0000407296.10524.d7 PG 7 WC Nursing SC Nursing GA 842HG UT WOS:000296586500017 PM 22005050 ER PT J AU Gerlock, AA Grimesey, JL Pisciotta, AK Harel, O AF Gerlock, April A. Grimesey, Jackie L. Pisciotta, Alisa K. Harel, Ofer TI Ask a Few More Questions SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material ID INTIMATE PARTNER VIOLENCE; NURSES; SCREEN; WOMEN C1 [Gerlock, April A.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Grimesey, Jackie L.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Tacoma, WA USA. [Harel, Ofer] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP Gerlock, AA (reprint author), Univ Washington, Sch Nursing, Seattle, WA 98195 USA. EM april.gerlock@va.gov FU NIMH NIH HHS [K01 MH087219] NR 18 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD NOV PY 2011 VL 111 IS 11 BP 35 EP 39 DI 10.1097/01.NAJ.0000407299.00222.ac PG 5 WC Nursing SC Nursing GA 842HG UT WOS:000296586500018 PM 22030925 ER PT J AU Winter, C Kampik, NB Vedovelli, L Rothenberger, F Paunescu, TG Stehberger, PA Brown, D John, H Wagner, CA AF Winter, Christian Kampik, Nicole B. Vedovelli, Luca Rothenberger, Florina Paunescu, Teodor G. Stehberger, Paul A. Brown, Dennis John, Hubert Wagner, Carsten A. TI Aldosterone stimulates vacuolar H+-ATPase activity in renal acid-secretory intercalated cells mainly via a protein kinase C-dependent pathway SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE collecting duct; kidney; receptor; signaling cascade ID MEDULLARY COLLECTING DUCT; THICK ASCENDING LIMB; NEM-SENSITIVE ATPASE; SMOOTH-MUSCLE-CELLS; MINERALOCORTICOID-RECEPTOR; STEROID-HORMONES; NONGENOMIC ACTIONS; NA+/H+-EXCHANGE; PROTON CONDUCTANCE; NEPHRON SEGMENTS AB Winter C, Kampik NB, Vedovelli L, Rothenberger F, Paunescu TG, Stehberger PA, Brown D, John H, Wagner CA. Aldosterone stimulates vacuolar H+-ATPase activity in renal acid-secretory intercalated cells mainly via a protein kinase C-dependent pathway. Am J Physiol Cell Physiol 301: C1251-C1261, 2011. First published August 10, 2011; doi: 10.1152/ajpcell.00076.2011.-Urinary acidification in the collecting duct is mediated by the activity of H+-ATPases and is stimulated by various factors including angiotensin II and aldosterone. Classically, aldosterone effects are mediated via the mineralocorticoid receptor. Recently, we demonstrated a nongenomic stimulatory effect of aldosterone on H+-ATPase activity in acid-secretory intercalated cells of isolated mouse outer medullary collecting ducts (OMCD). Here we investigated the intracellular signaling cascade mediating this stimulatory effect. Aldosterone stimulated H+-ATPase activity in isolated mouse and human OMCDs. This effect was blocked by suramin, a general G protein inhibitor, and GP-2A, a specific G(alpha q) inhibitor, whereas pertussis toxin was without effect. Inhibition of phospholipase C with U-73122, chelation of intracellular Ca2+ with BAPTA, and blockade of protein kinase C prevented the stimulation of H+-ATPases. Stimulation of PKC by DOG mimicked the effect of aldosterone on H+-ATPase activity. Similarly, aldosterone and DOG induced a rapid translocation of H+-ATPases to the luminal side of OMCD cells in vivo. In addition, PD098059, an inhibitor of ERK1/2 activation, blocked the aldosterone and DOG effects. Inhibition of PKA with H89 or KT2750 prevented and incubation with 8-bromoadenosine-cAMP mildly increased H+-ATPase activity. Thus, the nongenomic modulation of H+-ATPase activity in OMCD-intercalated cells by aldosterone involves several intracellular pathways and may be mediated by a G(alpha q) protein-coupled receptor and PKC. PKA and cAMP appear to have a modulatory effect. The rapid nongenomic action of aldosterone may participate in the regulation of H+-ATPase activity and contribute to final urinary acidification. C1 [Winter, Christian; Kampik, Nicole B.; Rothenberger, Florina; Stehberger, Paul A.; Wagner, Carsten A.] Univ Zurich, Inst Physiol, Ctr Integrat Human Physiol, CH-8057 Zurich, Switzerland. [Winter, Christian] Univ Hosp Dusseldorf, Urol Clin, Dusseldorf, Germany. [Vedovelli, Luca; Paunescu, Teodor G.; Brown, Dennis] Massachusetts Gen Hosp, MGH Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Vedovelli, Luca; Paunescu, Teodor G.; Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Paunescu, Teodor G.; Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. [Vedovelli, Luca] Univ Padua, Dept Pharmacol & Anesthesiol, Padua, Italy. [John, Hubert] Kantonsspital, Urol Clin, Winterthur, Switzerland. RP Wagner, CA (reprint author), Univ Zurich, Inst Physiol, Ctr Integrat Human Physiol, Winterthurerstr 190, CH-8057 Zurich, Switzerland. EM wagnerca@access.uzh.ch OI Vedovelli, Luca/0000-0003-4847-2333 FU Swiss National Research Foundation [31-068318, 31-109677/1]; National Institutes of Health (NIH) [DK-73266, DK-42956]; Boston Area Diabetes and Endocrinology Research Center [NIH DK-57521]; Center for the Study of Inflammatory Bowel Disease [NIH DK-43351] FX This study was supported by Swiss National Research Foundation Grants 31-068318 and 31-109677/1 (to C. A. Wagner). This work was also supported by National Institutes of Health (NIH) Grants DK-73266 (to T. G. Paunescu) and DK-42956 (to D. Brown). The Microscopy Core Facility of the Program in Membrane Biology received additional support from the Boston Area Diabetes and Endocrinology Research Center (NIH DK-57521) and from the Center for the Study of Inflammatory Bowel Disease (NIH DK-43351). NR 77 TC 22 Z9 22 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD NOV PY 2011 VL 301 IS 5 BP C1251 EP C1261 DI 10.1152/ajpcell.00076.2011 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 842GO UT WOS:000296583400029 PM 21832245 ER PT J AU Eddy, KT Rauch, SL AF Eddy, Kamryn T. Rauch, Scott L. TI Neuroimaging in Eating Disorders: Coming of Age SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID BULIMIA-NERVOSA C1 [Eddy, Kamryn T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. McLean Hosp, Belmont, MA USA. RP Eddy, KT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM kamryn@gmail.com NR 6 TC 4 Z9 4 U1 0 U2 3 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 NOV PY 2011 VL 168 IS 11 BP 1139 EP 1141 DI 10.1176/appi.ajp.2011.11071125 PG 3 WC Psychiatry SC Psychiatry GA 843FS UT WOS:000296658300004 PM 22193598 ER PT J AU Viguera, AC Tondo, L Koukopoulos, AE Reginaldi, D Lepri, B Baldessarini, RJ AF Viguera, Adele C. Tondo, Leonardo Koukopoulos, Alexia E. Reginaldi, Daniela Lepri, Beatrice Baldessarini, Ross J. TI Episodes of Mood Disorders in 2,252 Pregnancies and Postpartum Periods SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BIPOLAR DISORDER; RISK-FACTORS; ANTIDEPRESSANT TREATMENT; MENTAL-DISORDERS; WOMEN; DEPRESSION; DISCONTINUATION; CHILDBEARING; RECURRENCE; PSYCHOSES AB Objective: The risks of major affective episodes during pregnancy and during the postpartum period have rarely been compared in large samples across diagnoses. The authors hypothesized that perinatal episodes would mainly be depressive, would occur more in the postpartum than the prenatal period, and would be more prevalent with bipolar than unipolar depressive disorders. Method: The authors pooled clinical information on 2,252 pregnancies of 1,162 women with clinically treated DSM-IV bipolar I disorder (479 pregnancies/283 women), bipolar II disorder (641/338), or recurrent major depressive disorder (1,132/541) to compare rates of affective episode types by diagnosis during pregnancy and the postpartum period and to identify risk factors. Results: Among women with bipolar disorder, 23% had illness episodes during pregnancy and 52% during the postpartum period. Among women with unipolar depression, 4.6% had illness episodes during pregnancy and 30% during the postpartum period. Based on exposure-adjusted risk per pregnancy, episodes were 3.5 times more prevalent during the postpartum period than during pregnancy, and the risk was consistently higher with bipolar disorder. Depression was the most frequent morbidity during and following pregnancy. In multivariate modeling, factors associated with affective episodes in pregnancy, in descending order, were younger age at onset, previous postpartum episodes, fewer years of illness, bipolar disorder, fewer children, and not being married. Postpartum episodes were associated with younger age at onset, illness during pregnancy, bipolar disorder, fewer children, and more education. Moreover, pregnancy was less likely and perinatal episodes more likely if diagnosis preceded a first pregnancy. First lifetime episodes occurred in the perinatal period in 7.6% of cases. Conclusions: Among women with major affective disorders, illness risk was much greater during the postpartum period than during pregnancy. Illness mainly involved depression and was strongly associated with younger age at illness onset, bipolar disorder, and high lifetime occurrence rates. The relative risk during pregnancy compared with nonpregnant periods remains uncertain. C1 [Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McLean Hosp, Int Consortium Bipolar Disorder Res, Boston, MA USA. Cleveland Clin, Dept Psychiat, Neurol Inst, Cleveland, OH USA. Massachusetts Gen Hosp, Perinatal Unit, Boston, MA 02114 USA. Lucio Bini Mood Disorders Ctr, Cagliari, Sardinia, Italy. Lucio Bini Mood Disorders Ctr, Rome, Italy. RP Baldessarini, RJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. EM rbaldessarini@mclean.harvard.edu FU NIMH; Epilepsy Foundation; AstraZeneca; Bristol-Myers Squibb; Ortho-McNeil-Janssen Pharmaceuticals; Pfizer; Sunovion; NIH [MH-011609, MH-071762]; Lucio Bini Private Donors Mood Disorders Research Fund; McLean Private Donors Mood Disorders Research Fund; Bruce J. Anderson Foundation FX Dr. Viguera has received research support from NIMH, the Epilepsy Foundation, AstraZeneca, Bristol-Myers Squibb, Ortho-McNeil-Janssen Pharmaceuticals, Pfizer, and Sunovion and has served on the advisory board of Medco Health. The other authors report no financial relationships with commercial interests.; Supported in part by NIH grants MH-011609 and MH-071762 (to Dr. Viguera), the Lucio Bini Private Donors Mood Disorders Research Fund (to Dr. Tondo), a grant from the Bruce J. Anderson Foundation (to Dr. Baldessarini), and the McLean Private Donors Mood Disorders Research Fund (to Dr. Baldessarini). NR 40 TC 56 Z9 56 U1 0 U2 11 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 NOV PY 2011 VL 168 IS 11 BP 1179 EP 1185 DI 10.1176/appi.ajp.2011.11010148 PG 7 WC Psychiatry SC Psychiatry GA 843FS UT WOS:000296658300012 PM 21799064 ER PT J AU Malandraki, GA Hind, JA Gangnon, R Logemann, JA Robbins, J AF Malandraki, Georgia A. Hind, Jacqueline A. Gangnon, Ronald Logemann, Jeri A. Robbins, JoAnne TI The Utility of Pitch Elevation in the Evaluation of Oropharyngeal Dysphagia: Preliminary Findings SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE swallowing; voice; cricothyroid muscle; aspiration; pitch elevation ID PENETRATION-ASPIRATION SCALE; SUPERIOR LARYNGEAL NERVE; MULTIPLE IMPUTATION; VOICE; DISPLACEMENT; CLINICIAN; ANATOMY; STROKE; REFLEX; ADULTS AB Purpose: To evaluate the utility of a pitch elevation task in the assessment of oropharyngeal dysphagia. Method: This study was a pilot prospective cohort study including 40 consecutive patients (16 male and 24 female) who were referred by their physician for a swallowing evaluation. Patients were evaluated with a noninstrumental clinical examination and a videofluoroscopic swallow study, and participated in a pitch elevation task during videofluoroscopic image acquisition. Relationships between pitch elevation measurements (acoustic and perceptual) and swallow parameters (penetration/aspiration and residue) were investigated. Results: Results of this pilot study revealed that both maximum fundamental frequency (F(o)) and perceptual evaluation of pitch elevation independently significantly predicted Penetration-Aspiration Scale scores for thin liquid swallows (p = .01 and .03, respectively). Vocal range (average pitch to falsetto) was not sensitive in predicting likelihood of oropharyngeal dysphagia. Conclusions: Findings indicate that reduced pitch elevation can be indicative of reduced airway protection and swallowing impairment in some dysphagia patients and may be a useful supplement to dysphagia screening and diagnosis. Further investigation is warranted to determine the optimal utility of this procedure for different diagnostic categories of patients. C1 [Malandraki, Georgia A.; Hind, Jacqueline A.; Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Malandraki, Georgia A.; Hind, Jacqueline A.; Gangnon, Ronald; Robbins, JoAnne] Univ Wisconsin, Madison, WI 53706 USA. [Malandraki, Georgia A.] Columbia Univ, Teachers Coll, New York, NY 10027 USA. [Logemann, Jeri A.] Northwestern Univ, Evanston, IL USA. RP Malandraki, GA (reprint author), William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. EM malandraki@tc.columbia.edu NR 38 TC 4 Z9 5 U1 0 U2 1 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1058-0360 J9 AM J SPEECH-LANG PAT JI Am. J. Speech-Lang. Pathol. PD NOV 1 PY 2011 VL 20 IS 4 BP 262 EP 268 DI 10.1044/1058-0360(2011/10-0097) PG 7 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 844CE UT WOS:000296724500002 PM 21813823 ER PT J AU Sohani, AR Jaffe, ES Harris, NL Ferry, JA Pittaluga, S Hasserjian, RP AF Sohani, Aliyah R. Jaffe, Elaine S. Harris, Nancy Lee Ferry, Judith A. Pittaluga, Stefania Hasserjian, Robert P. TI Nodular Lymphocyte-Predominant Hodgkin Lymphoma With Atypical T Cells: A Morphologic Variant Mimicking Peripheral T-Cell Lymphoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE nodular lymphocyte-predominant Hodgkin lymphoma; LP cells; atypical T cells; peripheral T-cell lymphoma; IgD ID LARGE B-CELLS; DIFFERENTIAL-DIAGNOSIS; H-CELLS; DISEASE; EXPRESSION; IMMUNOGLOBULIN; CLASSIFICATION; TRANSFORMATION; PROLIFERATION; TRANSCRIPTION AB Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a distinct Hodgkin lymphoma subtype composed of few neoplastic lymphocyte-predominant (LP) cells in a background of reactive small B and T cells. We have seen occasional NLPHL cases that contain background T cells with prominent cytologic atypia, raising the differential diagnosis of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) or a composite lymphoma. We sought to characterize the clinicopathologic features of such cases. Eleven NLPHL cases with atypical T cells diagnosed from 1977 to 2010 were identified at 2 institutions and compared with 24 control NLPHL cases lacking atypical T cells. All 9 male patients and 2 female patients presented with localized peripheral lymphadenopathy. In comparison with control patients, they were younger (median age, 13.8 vs. 36.1 y; P = 0.015), with more frequent cervical lymph node involvement (54.5% vs. 8.3%, P = 0.015). In all 11 cases, areas of NLPHL with typical B-cell-rich nodules containing LP cells were present. Nine cases contained sheets of atypical T cells surrounding primary and secondary follicles in a pattern mimicking the T-zone pattern of PTCL-NOS; the remaining 2 cases contained atypical T cells presented as large clusters at the periphery of B-cell-rich nodules. In all cases, the atypical T-cell-rich areas contained rare scattered LP cells, which were IgD(+) in 5 of 7 cases (71.4%). The atypical T cells showed no pan-T-cell antigen loss or aberrant T-cell antigen expression in any case, and polymerase chain reaction or Southern blot analysis showed no evidence of T-cell clonality in 6 cases tested. The atypical T cells exhibited a variable immunophenotype with respect to germinal center, follicular T-helper, T-regulatory, and cytotoxic T-cell markers. Among 8 patients with clinical follow-up (median follow-up: 6.4 y), 5 patients had recurrent NLPHL at 6 months to 12 years after diagnosis and 6 patients are alive without disease at 9 months to 18 years after diagnosis. In comparison with control patients, NLPHL patients with atypical T cells were more likely to develop recurrent NLPHL (71.4% vs. 13.6%, P = 0.008) and to have a shorter time to relapse (P = 0.04). Our findings suggest that some cases of NLPHL, occurring predominantly in younger patients, contain prominent populations of morphologically atypical T cells that may raise the possibility of concurrent nodal involvement by PTCL-NOS, a rare diagnosis in children. The clinical behavior of these cases appears similar to that of NLPHL with T-cell-rich diffuse areas, with a higher risk of disease recurrence and no difference in overall survival; however, this finding warrants confirmation in studies of larger numbers of patients. C1 [Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Sohani, Aliyah R.; Harris, Nancy Lee; Ferry, Judith A.; Hasserjian, Robert P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Jaffe, Elaine S.; Pittaluga, Stefania] NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Sohani, AR (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, 55 Fruit St,WRN 219, Boston, MA 02114 USA. EM arsohani@partners.org OI Jaffe, Elaine/0000-0003-4632-0301 NR 48 TC 17 Z9 19 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2011 VL 35 IS 11 BP 1666 EP 1678 DI 10.1097/PAS.0b013e31822832de PG 13 WC Pathology; Surgery SC Pathology; Surgery GA 842DJ UT WOS:000296569500007 PM 21997687 ER PT J AU Lincoln, R Rosenthal, CF Malte, CA Simpson, T AF Lincoln, Randi Rosenthal, Christina F. Malte, Carol A. Simpson, Tracy TI A Pilot Study of Memory Impairment Associated with Discrepancies between Retrospective and Daily Recall of Alcohol Consumption SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID INTERACTIVE VOICE RESPONSE; AUTOBIOGRAPHICAL MEMORY; MEASURE DRINKING; TECHNOLOGY AB Prior studies have found discrepancies between daily report and retrospective recall of alcohol use. One possible explanation is that there may be an association between memory impairment and alcohol consumption recall errors. Should this possibility be substantiated it could have implications for the types of assessments conducted in alcohol treatment trials. The current study evaluated the degree to which memory impairment, as measured by the California Verbal Learning Test-II, predicted day-to-day discrepancies between daily Interactive Voice Response monitoring and retrospective recall of alcohol use assessed with a 42-day version of the Form-90. Significant differences were detected in absolute difference in days drinking across the two measurement methods between participants scoring above and below population means on two measures of immediate memory ability. Correlations between the absolute difference in days drinking and immediate memory ability and long-delay memory indices approached significance. There were no significant associations between memory indices and discrepancies in reports of standard drink units. These preliminary results suggest that verbal memory difficulties common in this population may result in inaccurate reports of days drinking for some individuals. (Am J Addict 2011;20:568-574) C1 [Lincoln, Randi] VA Puget Sound Hlth Care Syst, Spinal Cord Injury Ctr Excellence, Seattle, WA 98108 USA. [Rosenthal, Christina F.; Simpson, Tracy] Seattle Inst Biomed & Clin Res, Seattle, WA USA. [Malte, Carol A.; Simpson, Tracy] Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [Simpson, Tracy] VISN 20 Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Simpson, Tracy] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Simpson, T (reprint author), VA Puget Sound Hlth Care Syst, Spinal Cord Injury Ctr Excellence, 1660 S Columbian Way ATC 116-S, Seattle, WA 98108 USA. EM Tracy.Simpson@va.gov NR 20 TC 5 Z9 5 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD NOV-DEC PY 2011 VL 20 IS 6 BP 568 EP 574 DI 10.1111/j.1521-0391.2011.00178.x PG 7 WC Substance Abuse SC Substance Abuse GA 840EB UT WOS:000296420000011 PM 21999504 ER PT J AU Mhyre, JM Bateman, BT Leffert, LR AF Mhyre, Jill M. Bateman, Brian T. Leffert, Lisa R. TI Influence of Patient Comorbidities on the Risk of Near-miss Maternal Morbidity or Mortality SO ANESTHESIOLOGY LA English DT Article ID PREGNANCY-RELATED MORTALITY; SEVERE OBSTETRIC MORBIDITY; UNITED-STATES; INTENSIVE-CARE; MULTIFETAL PREGNANCIES; HYPERTENSIVE DISORDERS; ADVERSE OUTCOMES; ASTHMATIC WOMEN; POPULATION; DELIVERIES AB Background: Maternal morbidity and mortality are increased in the United States compared with that of other developed countries. The objective of this investigation is to determine the extent to which it is possible to predict which patients will experience near-miss morbidity or mortality. Methods: The authors defined near-miss morbidity as end-organ injury associated with length of stay greater than the 99(th) percentile or discharge to a second medical facility, and identified all cases of near-miss morbidity or death from admissions for delivery in the 2003-2006 Nationwide Inpatient Sample. Logistic regression was used to examine the effect of maternal characteristics on rates of near-miss morbidity/mortality. Results: Approximately 1.3 per 1,000 hospitalizations for delivery was complicated by near-miss morbidity/mortality as defined in this study (95% CI 1.3-1.4). Most of these events (58.3%) occurred in 11.8% of the delivering population-in those women with important medical comorbidities or obstetric complications identified before admission for delivery. The highest rates were noted among women with pulmonary hypertension (98.0 cases per 1,000 deliveries), malignancy (23.4 per 1,000), and systemic lupus erythematosus (21.1 per 1,000). Conclusions: Risk for near-miss morbidity or mortality is substantially increased among an identifiable subset of pregnant women. To the extent that antepartum multidisciplinary coordination and high-quality intrapartum care improve delivery outcomes for women with significant antepartum medical and obstetric disease, then public health investments to reduce the national burden of delivery-related near-miss morbidity and mortality will have the greatest effect by focusing resources on identifying and serving these high-risk groups. C1 [Mhyre, Jill M.] Univ Michigan Hlth Syst, Dept Anesthesiol, Div Obstetr Anesthesia, Ann Arbor, MI 48105 USA. Harvard Univ, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Massachusetts Gen Hosp, Boston, MA USA. RP Mhyre, JM (reprint author), Univ Michigan Hlth Syst, Dept Anesthesiol, Div Obstetr Anesthesia, Womens Hosp SPC 5278,Room L3622,1500 E Med Ctr Dr, Ann Arbor, MI 48105 USA. EM jmmhyre@umich.edu NR 66 TC 33 Z9 35 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2011 VL 115 IS 5 BP 963 EP 972 DI 10.1097/ALN.0b013e318233042d PG 10 WC Anesthesiology SC Anesthesiology GA 842AR UT WOS:000296558400012 PM 21934482 ER PT J AU Francis, RC Vaporidi, K Bloch, KD Ichinose, F Zapol, WM AF Francis, Roland C. Vaporidi, Katerina Bloch, Kenneth D. Ichinose, Fumito Zapol, Warren M. TI Protective and Detrimental Effects of Sodium Sulfide and Hydrogen Sulfide in Murine Ventilator-induced Lung Injury SO ANESTHESIOLOGY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; OXIDATIVE STRESS; NITRIC-OXIDE; RATS; MICE; PATHOGENESIS; INFLAMMATION; CONTRIBUTES; MECHANISMS AB Background: The antiinflammatory effects of hydrogen sulfide (H2S) and sodium sulfide (Na2S) treatment may prevent acute lung injury induced by high tidal volume (HVT) ventilation. However, lung protection may be limited by direct pulmonary toxicity associated with H2S inhalation. Therefore, the authors tested whether the inhalation of H2S or intravascular Na2S treatment can protect against ventilator-induced lung injury in mice. Methods: Anesthetized mice continuously inhaled 0, 1, 5, or 60 ppm H2S or received a single bolus infusion of Na2S (0.55 mg/kg) or vehicle and were then subjected to HVT (40 ml/kg) ventilation lasting 4 h (n = 4-8 per group). Results: HVT ventilation increased the concentrations of protein and interleukin-6 in bronchoalveolar lavage fluid, contributing to reduced respiratory compliance and impaired arterial oxygenation, and caused death from lung injury and pulmonary edema. Inhalation of 1 or 5 ppm H2S during HVT ventilation did not alter lung injury, but inhalation of 60 ppm H2S accelerated the development of ventilator-induced lung injury and enhanced the pulmonary expression of the chemoattractant CXCL-2 and the leukocyte adhesion molecules CD11b and L-selectin. In contrast, pretreatment with Na2S attenuated the expression of CXCL-2 and CD11b during HVT ventilation and reduced pulmonary edema. Moreover, Na2S enhanced the pulmonary expression of Nrf2-dependent antioxidant genes (NQO1, GPX2, and GST-A4) and prevented oxidative stress-induced depletion of glutathione in lung tissue. Conclusions: The data suggest that systemic intravascular treatment with Na2S represents a novel therapeutic strategy to prevent both ventilator-induced lung injury and pulmonary glutathione depletion by activating Nrf2-dependent antioxidant gene transcription. C1 [Zapol, Warren M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med,Anesthesia C, Boston, MA 02114 USA. [Francis, Roland C.; Vaporidi, Katerina; Zapol, Warren M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med,Anesthesia C, 55 Fruit St, Boston, MA 02114 USA. EM wzapol@partners.org FU German Research Foundation (Deutsche Forschungsgemeinschaft, Bonn, Germany) [FR 2555/3-1]; United States Public Health Service, Washington, D.C. [HL074352, HL101930] FX Supported by fellowship grant FR 2555/3-1 (to Dr. Francis) from the German Research Foundation (Deutsche Forschungsgemeinschaft, Bonn, Germany); royalties from Ikaria Inc., Hampton, New Jersey, and Linde Corp, Murray Hill, New Jersey (to Dr. Zapol); and grants HL074352 (to Dr. Bloch) and HL101930 (to Dr. Ichinose) from the United States Public Health Service, Washington, D.C. NR 29 TC 25 Z9 29 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2011 VL 115 IS 5 BP 1012 EP 1021 DI 10.1097/ALN.0b013e31823306cf PG 10 WC Anesthesiology SC Anesthesiology GA 842AR UT WOS:000296558400017 PM 21912243 ER PT J AU Wallace, AW Au, S Cason, BA AF Wallace, Arthur W. Au, Selwyn Cason, Brian A. TI How Often Should Atenolol Be Dosed for Perioperative beta-Blockade? Reply SO ANESTHESIOLOGY LA English DT Letter ID MORTALITY C1 [Wallace, Arthur W.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Wallace, AW (reprint author), San Francisco VA Med Ctr, San Francisco, CA USA. EM awallace@cardiacengineering.com NR 4 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2011 VL 115 IS 5 BP 1140 EP 1141 DI 10.1097/ALN.0b013e3182334092 PG 4 WC Anesthesiology SC Anesthesiology GA 842AR UT WOS:000296558400040 ER PT J AU Ebaugh, JL Gupta, N Raffetto, JD AF Ebaugh, James L. Gupta, Naren Raffetto, Joseph D. TI Single-Incision External Iliac Artery Endarterectomy and Patch Angioplasty SO ANNALS OF VASCULAR SURGERY LA English DT Article ID AORTOILIAC OCCLUSIVE DISEASE; BALLOON ANGIOPLASTY; BYPASS AB An isolated external iliac artery chronic total occlusion is currently treated either with subintimal percutaneous transluminal angioplasty and stent or with a bypass. This article describes a new application of an old technique, endarterectomy and patch angioplasty, performed on the external iliac artery through a single flank incision. This novel approach can provide lasting patency with a low risk of complications. We present four cases and a review of the literature on the other available treatment options. This minimally invasive technique may provide a viable alternative that can be used alone or in combination with other open or endovascular techniques and can be applied in cases of groin sepsis. C1 [Ebaugh, James L.; Gupta, Naren; Raffetto, Joseph D.] VA Boston Healthcare Syst, Surg Serv, W Roxbury, MA 02132 USA. [Ebaugh, James L.; Gupta, Naren; Raffetto, Joseph D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. RP Ebaugh, JL (reprint author), VA Boston Healthcare Syst, Surg Serv 112, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM james.ebaugh2@med.va.gov NR 20 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 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD NOV PY 2011 VL 25 IS 8 BP 1165 EP 1169 DI 10.1016/j.avsg.2011.05.032 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 841ZG UT WOS:000296553100040 PM 22023946 ER PT J AU Hynes, B Goodenough, RD Slovut, DP AF Hynes, Brian Goodenough, Richard D. Slovut, David P. TI Carotid Artery Stenting After Carotid Endarterectomy SO ANNALS OF VASCULAR SURGERY LA English DT Article ID MANDIBULAR SUBLUXATION; PROTECTION DEVICES; INTRAOPERATIVE USE; END-POINTS; SHORT-TERM; STENOSIS; PREVENTION; MANAGEMENT; EXPOSURE; STROKES AB Atherosclerotic carotid artery disease remains an important cause of cerebrovascular ischemic disease. We present a patient with residual stenosis of the distal internal carotid artery following carotid endarterectomy that was treated with stenting. The case highlights the potential complimentary benefits of carotid endarterectomy and carotid stenting. C1 [Hynes, Brian] Massachusetts Gen Hosp, Dept Cardiol, Sect Vasc Med & Peripheral Intervent, Boston, MA 02114 USA. [Goodenough, Richard D.] N Shore Med Ctr, Vasc Surg Sect, Salem, MA USA. [Slovut, David P.] Montefiore Med Ctr, Div Cardiol, Bronx, NY 10467 USA. [Slovut, David P.] Montefiore Med Ctr, Div Vasc Surg, Bronx, NY 10467 USA. RP Hynes, B (reprint author), Massachusetts Gen Hosp, Div Cardiol, Sect Vasc Med & Intervent, 55 Fruit St, Boston, MA 02114 USA. EM bhynes@hotmail.com NR 25 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 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD NOV PY 2011 VL 25 IS 8 AR 1143.e1 DI 10.1016/j.avsg.2011.08.006 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 841ZG UT WOS:000296553100036 PM 22023956 ER PT J AU Bassett, EK Hoganson, DM Lo, JH Penson, EJN Vacanti, JP AF Bassett, Erik K. Hoganson, David M. Lo, Justin H. Penson, Elliot J. N. Vacanti, Joseph P. TI Influence of Vascular Network Design on Gas Transfer in Lung Assist Device Technology SO ASAIO JOURNAL LA English DT Article ID CARBON-DIOXIDE REMOVAL; MICROCHANNEL TECHNOLOGIES; MEMBRANE-OXYGENATOR; MATHEMATICAL-MODEL; ARTIFICIAL LUNGS; RECTANGULAR CHANNELS; BLOOD; TRANSPLANTATION; POLY(DIMETHYLSILOXANE); CAPILLARIES AB Blood oxygenators are vital for the critically ill, but their use is limited to the hospital setting. A portable blood oxygenator or a lung assist device for ambulatory or long-term use would greatly benefit patients with chronic lung disease. In this work, a biomimetic blood oxygenator system was developed which consisted of a microfluidic vascular network covered by a gas permeable silicone membrane. This system was used to determine the influence of key microfluidic parameters-channel size, oxygen exposure length, and blood shear rate-on blood oxygenation and carbon dioxide removal. Total gas transfer increased linearly with flow rate, independent of channel size and oxygen exposure length. On average, CO(2) transfer was 4.3 times higher than oxygen transfer. Blood oxygen saturation was also found to depend on the flow rate per channel but in an inverse manner; oxygenation decreased and approached an asymptote as the flow rate per channel increased. These relationships can be used to optimize future biomimetic vascular networks for specific lung applications: gas transfer for carbon dioxide removal in patients with chronic obstructive pulmonary disease or oxygenation for premature infants requiring complete lung replacement therapy. ASAIO Journal 2011; 57:533-538. C1 [Bassett, Erik K.; Hoganson, David M.; Lo, Justin H.; Penson, Elliot J. N.; Vacanti, Joseph P.] Massachusetts Gen Hosp, Dept Surg, Ctr Regenerat Med, Boston, MA 02114 USA. [Bassett, Erik K.; Hoganson, David M.; Lo, Justin H.; Penson, Elliot J. N.; Vacanti, Joseph P.] MassGen Hosp Children, Boston, MA USA. [Lo, Justin H.; Vacanti, Joseph P.] Harvard Univ, Sch Med, Boston, MA USA. RP Vacanti, JP (reprint author), Dept Pediat Surg, 55 Fruit St,Warren 1151, Boston, MA 02114 USA. EM jvacanti@partners.org OI Hoganson, David/0000-0002-8141-7793 FU NIH [F32 DK076349-01]; Health Resources and Services Administration [234-2005-37011C] FX This work was supported by the NIH (F32 DK076349-01, to D. M. H.) and in part by Health Resources and Services Administration contract 234-2005-37011C. NR 32 TC 4 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD NOV-DEC PY 2011 VL 57 IS 6 BP 533 EP 538 DI 10.1097/MAT.0b013e318234a3ac PG 6 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 842IE UT WOS:000296590100010 PM 22036722 ER PT J AU Kurusu, S Sapirstein, A Sawada, H Kawaminami, M Bonventre, JV AF Kurusu, Shiro Sapirstein, Adam Sawada, Harumi Kawaminami, Mitsumori Bonventre, Joseph V. TI Group IVA phospholipase A(2) regulates testosterone biosynthesis by murine Leydig cells and is required for timely sexual maturation SO BIOCHEMICAL JOURNAL LA English DT Article DE arachidonic acid; Group IVA phospholipase A(2) (PLA(2)G4A); Leydig cell; sexual maturation; testosterone ID MALE REPRODUCTIVE-ORGANS; GROUP-II PHOSPHOLIPASE-A2; SPERM ACROSOME REACTION; ARACHIDONIC-ACID; CYTOSOLIC PHOSPHOLIPASE-A(2)ALPHA; STIMULATED STEROIDOGENESIS; RECOMBINANT EXPRESSION; REDUCED FERTILITY; GENE-EXPRESSION; FATTY-ACIDS AB In the present paper, we report that PLA(2)G4A (Group IVA phospholipase A(2)) is important in the development and function of rodent testes. Interstitial cells of rat testes had high PLA(2) (phospholipase A(2)) activity that was very sensitive to the PLA(2)G4A-preferential inhibitor AACOCF(3) (arachidonyl trifluoromethyl ketone). PLA(2)G4A protein was expressed primarily in the interstitial cells of wild-type mouse testes throughout maturation. Although Pla2g4a knockout (Pla2g4a(-/-)) male mice are fertile, their sexual maturation was delayed, as indicated by cauda epididymal sperm count and seminal vesicle development. Delayed function of Pla2g4a(-/-) mice testes was associated with histological abnormalities including disorganized architecture, swollen appearance and fewer interstitial cells. Basal secretion of testosterone was attenuated significantly and steroidogenic response to hCG (human chorionic gonadotropin) treatment was reduced in Pla2g4a(-/-) mice compared with their Pla2g4a(+/+) littermates during the sexual maturation period. Chemical inhibition of PLA(2)G4A activity by AACOCF(3) or pyrrophenone significantly reduced hCG-stimulated testosterone production in cultured rat interstitial cells. AACOCF(3) inhibited forskolin- and cAMP analogue-stimulated testosterone production. These results provide the first evidence that PLA(2)G4A plays a role in male testes physiology and development. These results may have implications for the potential clinical use of PLA(2)G4A inhibitors. C1 [Kurusu, Shiro; Bonventre, Joseph V.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kurusu, Shiro; Sawada, Harumi; Kawaminami, Mitsumori] Kitasato Univ, Sch Vet Med, Vet Physiol Lab, Aomori 0348628, Japan. [Sapirstein, Adam] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Bonventre, Joseph V.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Bonventre, Joseph V.] Holyoke Ctr, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Bonventre, JV (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM jbonventre@partners.org FU National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [DK39773, DK54741]; Nakayama Foundation for Human Science FX The work done in the laboratory of J.V.B. was supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [grant numbers DK39773 and DK54741]. S.K. received a fellowship for studies abroad from the Nakayama Foundation for Human Science. NR 58 TC 3 Z9 3 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 1 PY 2011 VL 439 BP 403 EP 411 DI 10.1042/BJ20102167 PN 3 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 841XK UT WOS:000296548300005 PM 21762109 ER PT J AU Tanrikut, C Goldstein, M Rosoff, JS Lee, RK Nelson, CJ Mulhall, JP AF Tanrikut, Cigdem Goldstein, Marc Rosoff, James S. Lee, Richard K. Nelson, Christian J. Mulhall, John P. TI Varicocele as a risk factor for androgen deficiency and effect of repair SO BJU INTERNATIONAL LA English DT Article DE varicocele; testosterone; hypogonadism; androgen deficiency ID INFERTILE MEN; TESTICULAR TEMPERATURE; TESTOSTERONE LEVELS; OLDER MEN; PLASMA; AGE; POPULATION; PREVALENCE; FERTILITY; PITUITARY AB OBJECTIVE To determine whether men with varicoceles have lower testosterone levels than those without and to ascertain if testosterone levels increase after varicocelectomy. PATIENTS AND METHODS We measured preoperative testosterone levels in 325 men with palpable varicoceles and in 510 men with vasectomy reversal without varicoceles who served as a comparison group. The testosterone levels between groups were compared by age. Of the men with varicoceles, 200 had data on both pre- and postoperative testosterone levels, which were compared to assess postoperative changes. RESULTS Men with varicocele had significantly lower testosterone levels than the comparison group, with mean (SD) levels of 416 (156) vs 469 (192) ng/dL (P < 0.001). This difference persisted when analysed by age. The testosterone levels significantly increased after repair from 358 (126) to 454 (168) ng/dL (P < 0.001). Of the 70% of patients with postoperative improvement in testosterone levels, the mean (SD) increase in testosterone was 178 (142) ng/dL. The percentage change in testosterone levels was: 30% had no increase, 41% increased by <= 50%, 19% increased between by 51-100%, and 10% increased by >100%. There was no association between change in testosterone level and age, laterality of varicocele, or varicocele grade. CONCLUSIONS Men with varicoceles had significantly lower testosterone levels than the comparison group of men with vasectomy reversal. Microsurgical varicocele ligation resulted in a significant increase in serum testosterone levels in more than two-thirds of men. These findings suggest that varicocele is a significant risk factor for androgen deficiency and that repair may increase testosterone levels in men with varicocele and low testosterone levels. C1 [Tanrikut, Cigdem] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tanrikut, Cigdem; Goldstein, Marc; Rosoff, James S.; Lee, Richard K.; Mulhall, John P.] Cornell Univ, Weill Cornell Med Coll, Boston, MA USA. [Tanrikut, Cigdem] Harvard Univ, Sch Med, New York, NY USA. [Goldstein, Marc; Rosoff, James S.; Lee, Richard K.] New York Presbyterian Hosp, New York, NY USA. [Goldstein, Marc] Populat Council, Ctr Biomed Res, New York, NY 10021 USA. [Nelson, Christian J.; Mulhall, John P.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Tanrikut, C (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 10A, Boston, MA 02114 USA. EM ctanrikut@partners.org FU New York Community Trust FX The authors thank Joshua Bloomberg, Judy Choi, and Sam Finkelberg, RN for data accumulation and data entry. This study was supported by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust. NR 32 TC 47 Z9 52 U1 0 U2 10 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 NOV PY 2011 VL 108 IS 9 BP 1480 EP 1484 DI 10.1111/j.1464-410X.2010.10030.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 846MA UT WOS:000296905800021 PM 21435152 ER PT J AU Wu, WW Johnson, R Schepp, KG Berry, DL AF Wu, Wei-Wen Johnson, Rebecca Schepp, Karen G. Berry, Donna L. TI Electronic Self-report Symptom and Quality of Life for Adolescent Patients With Cancer A Feasibility Study SO CANCER NURSING LA English DT Article DE Acceptability; Adolescent; Cancer; Cancer symptom; Computerized assessment; Computerized questionnaire; Feasibility; Quality of life; Web-based technology ID CLINICAL-TRIALS; CHILDHOOD-CANCER; YOUNG-ADULTS; HEALTH; CHILDREN; PROGRAM; CARE; WEB; QUESTIONNAIRES; ACCEPTABILITY AB Background: Computerized symptom and quality of life (QoL) assessment has been tested and found feasible and acceptable in outpatient settings for adult patients with cancer, but has not been used often in pediatric oncology settings in the United States. Objective: The purpose of this pilot study was to evaluate the feasibility of an innovative, computerized symptom, and QoL assessment for adolescent patients who were being treated for cancer. Methods: A convenience sample of 40 adolescent patients with cancer, who were between 13 and 20 years old and able to communicate in English, agreed to participate. Each participant answered the Web-based Electronic Self-report Assessment-Cancer Adolescent Form on a wireless touch-screen computer just prior to a treatment visit in an ambulatory clinic setting. Descriptive frequencies and central tendency were used to describe sample characteristics and feasibility outcomes. Results: The computerized assessment was found to be feasible with regard to data completeness rates (>99%), acceptability (high), time to complete (30 minutes), and assistance required to complete (minimal). Conclusion: The Electronic Self-report Assessment-Cancer Adolescent Form is a feasible approach for obtaining adolescent patients' self-report of cancer symptoms and QoL in an ambulatory setting. Implications for Practice: Screening for symptoms and QoL may be integrated during check-in procedures as routine assessment for adolescent cancer patients in ambulatory settings. C1 [Berry, Donna L.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. [Wu, Wei-Wen] Natl Taipei Univ, Nursing & Hlth Sci Sch Nursing, Dept Nursing, Taipei, Taiwan. [Johnson, Rebecca] Childrens Hosp, Seattle, WA USA. [Schepp, Karen G.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. RP Berry, DL (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Phyllis F Cantor Ctr Res Nursing & Patient Care S, 405 Brookline Ave,CP 305, Boston, MA 02115 USA. EM donna_berry@dfci.harvard.edu OI Wu, Wei-Wen/0000-0002-6439-5369 FU School of Nursing, University of Washington; Sigma Theta Tau PSI-at-Large Chapter; Hematology/Oncology and Orthopedics clinics at Seattle Children FX Funding was received from Hester McLaws Fund, School of Nursing, University of Washington, and the Sigma Theta Tau PSI-at-Large Chapter.; The authors thank all participants and their parents for their time and effort in sharing their experiences. Many thanks to the Hematology/Oncology and Orthopedics clinics at Seattle Children's for supporting this study, particularly Dr Ernest Conrad, Elizabeth Scholzen, and Sarah Young. NR 55 TC 5 Z9 5 U1 4 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0162-220X EI 1538-9804 J9 CANCER NURS JI Cancer Nurs. PD NOV-DEC PY 2011 VL 34 IS 6 BP 479 EP 486 DI 10.1097/NCC.0b013e31820a5bdd PG 8 WC Oncology; Nursing SC Oncology; Nursing GA 842RA UT WOS:000296615800011 PM 21372703 ER PT J AU Zhang, CP Wang, LG Wu, DY Chen, HY Chen, Z Thomas-Ahner, JM Zynger, DL Eeckhoute, J Yu, JD Luo, J Brown, M Clinton, SK Nephew, KP Huang, THM Li, W Wang, QB AF Zhang, Chunpeng Wang, Liguo Wu, Dayong Chen, Hongyan Chen, Zhong Thomas-Ahner, Jennifer M. Zynger, Debra L. Eeckhoute, Jerome Yu, Jindan Luo, Jun Brown, Myles Clinton, Steven K. Nephew, Kenneth P. Huang, Tim H. -M. Li, Wei Wang, Qianben TI Definition of a FoxA1 Cistrome That Is Crucial for G(1) to S-Phase Cell-Cycle Transit in Castration-Resistant Prostate Cancer SO CANCER RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR; ANDROGEN RECEPTOR; REGULATORY ELEMENTS; IN-VITRO; CHROMATIN; BINDING; EXPRESSION; PROGRESSION; NUCLEOSOME; SIGNATURES AB The enhancer pioneer transcription factor FoxA1 is a global mediator of steroid receptor (SR) action in hormone-dependent cancers. In castration-resistant prostate cancer (CRPC), FoxA1 acts as an androgen receptor cofactor to drive G(2) to M-phase cell-cycle transit. Here, we describe a mechanistically distinct SR-independent role for FoxA1 in driving G(1) to S-phase cell-cycle transit in CRPC. By comparing FoxA1 binding sites in prostate cancer cell genomes, we defined a codependent set of FoxA1-MYBL2 and FoxA1-CREB1 binding sites within the regulatory regions of the Cyclin E2 and E2F1 genes that are critical for CRPC growth. Binding at these sites upregulate the Cyclin E2 and Cyclin A2 genes in CRPC but not in earlier stage androgen-dependent prostate cancer, establishing a stage-specific role for this pathway in CRPC growth. Mechanistic investigations indicated that FoxA1, MYBL2, or CREB1 induction of histone H3 acetylation facilitated nucleosome disruption as the basis for codependent transcriptional activation and G(1) to S-phase cell-cycle transit. Our findings establish FoxA1 as a pivotal driver of the cell-cycle in CRPC which promotes G(1) to S-phase transit as well as G(2) to M-phase transit through two distinct mechanisms. Cancer Res; 71(21); 6738-48. (C)2011 AACR. C1 [Zhang, Chunpeng; Wu, Dayong; Chen, Hongyan; Chen, Zhong; Wang, Qianben] Ohio State Univ, Coll Med, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. [Zhang, Chunpeng; Wu, Dayong; Chen, Hongyan; Chen, Zhong; Thomas-Ahner, Jennifer M.; Clinton, Steven K.; Wang, Qianben] Ohio State Univ, Coll Med, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Thomas-Ahner, Jennifer M.; Clinton, Steven K.] Ohio State Univ, Coll Med, Div Med Oncol, Dept Internal Med, Columbus, OH 43210 USA. [Zynger, Debra L.] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43210 USA. [Huang, Tim H. -M.] Ohio State Univ, Human Canc Genet Program, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Wang, Liguo; Li, Wei] Baylor Coll Med, Div Biostat, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Wang, Liguo; Li, Wei] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Eeckhoute, Jerome] Univ Lille Nord France, Fac Med Lille Pole Rech, INSERM UMR Batiment J&K 1011, Lille, France. [Yu, Jindan] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Yu, Jindan] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Luo, Jun] Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA. [Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Brown, Myles] Harvard Univ, Sch Med, Boston, MA USA. [Nephew, Kenneth P.] Indiana Univ, Sch Med, Med Sci Program, Dept Cellular & Integrat Physiol, Bloomington, IN 47405 USA. RP Wang, QB (reprint author), Ohio State Univ, Coll Med, Dept Mol & Cellular Biochem, 888 Biomed Res Tower,460 W 12th Ave, Columbus, OH 43210 USA. EM WL1@bcm.edu; qianben.wang@osumc.edu RI Wang, Qianben/E-4267-2011; Thomas-Ahner, Jennifer/I-7598-2013; Thomas-Ahner, Jennifer/M-3955-2015; OI Thomas-Ahner, Jennifer/0000-0001-5264-7592; Brown, Myles/0000-0002-8213-1658; Eeckhoute, Jerome/0000-0002-7222-9264 FU NIH [R00 CA126160, U54 CA113001]; DOD [PC094421]; Ohio State University Comprehensive Cancer Center FX This work was supported by NIH grants R00 CA126160 (to Q. Wang and W. Li) and U54 CA113001 (to Q.Wang, K.P. Nephew, and T.H.M. Huang), DOD grant PC094421 (to W. Li), and the Ohio State University Comprehensive Cancer Center (to Q. Wang and T.H.M. Huang). NR 46 TC 40 Z9 43 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2011 VL 71 IS 21 BP 6738 EP 6748 DI 10.1158/0008-5472.CAN-11-1882 PG 11 WC Oncology SC Oncology GA 842ML UT WOS:000296603500020 PM 21900400 ER PT J AU Bhalla, K Hwang, BJ Dewi, RE Ou, LH Twaddel, W Fang, HB Vafai, SB Vazquez, F Puigserver, P Boros, L Girnun, GD AF Bhalla, Kavita Hwang, Bor Jang Dewi, Ruby E. Ou, Lihui Twaddel, William Fang, Hong-Bin Vafai, Scott B. Vazquez, Francesca Puigserver, Pere Boros, Laszlo Girnun, Geoffrey D. TI PGC1 alpha Promotes Tumor Growth by Inducing Gene Expression Programs Supporting Lipogenesis SO CANCER RESEARCH LA English DT Article ID ESTROGEN-RELATED RECEPTOR; FATTY-ACID SYNTHESIS; OXIDATIVE-PHOSPHORYLATION; BREAST-CANCER; PPAR-GAMMA; ENERGY-METABOLISM; NUCLEAR RECEPTORS; CELL-GROWTH; ERR-ALPHA; PGC-1 AB Despite the role of aerobic glycolysis in cancer, recent studies highlight the importance of the mitochondria and biosynthetic pathways as well. PPAR gamma coactivator 1 alpha (PGC1 alpha) is a key transcriptional regulator of several metabolic pathways including oxidative metabolism and lipogenesis. Initial studies suggested that PGC1 alpha expression is reduced in tumors compared with adjacent normal tissue. Paradoxically, other studies show that PGC1 alpha is associated with cancer cell proliferation. Therefore, the role of PGC1 alpha in cancer and especially carcinogenesis is unclear. Using Pgc1 alpha(-/-) and Pgc1 alpha(+/+) mice, we show that loss of PGC1 alpha protects mice from azoxymethane-induced colon carcinogenesis. Similarly, diethylnitrosamine-induced liver carcinogenesis is reduced in Pgc1 alpha(-/-) mice as compared with Pgc1 alpha(+/+) mice. Xenograft studies using gain and loss of PGC1 alpha expression showed that PGC1 alpha also promotes tumor growth. Interestingly, while PGC1 alpha induced oxidative phosphorylation and tricarboxylic acid cycle gene expression, we also observed an increase in the expression of two genes required for de novo fatty acid synthesis, ACC and FASN. In addition, SLC25A1 and ACLY, which are required for the conversion of glucose into acetyl-CoA for fatty acid synthesis, were also increased by PGC1 alpha, thus linking the oxidative and lipogenic functions of PGC1 alpha. Indeed, using stable C-13 isotope tracer analysis, we show that PGC1 alpha increased de novo lipogenesis. Importantly, inhibition of fatty acid synthesis blunted these progrowth effects of PGC1 alpha. In conclusion, these studies show for the first time that loss of PGC1 alpha protects against carcinogenesis and that PGC1 alpha coordinately regulates mitochondrial and fatty acid metabolism to promote tumor growth. Cancer Res; 71(21); 6888-98. (C) 2011 AACR. C1 [Bhalla, Kavita; Hwang, Bor Jang; Dewi, Ruby E.; Ou, Lihui; Fang, Hong-Bin; Girnun, Geoffrey D.] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. [Twaddel, William] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Vafai, Scott B.; Vazquez, Francesca; Puigserver, Pere] Harvard Univ, Sch Med, Boston, MA USA. [Vazquez, Francesca; Puigserver, Pere] Dana Farber Canc Inst, Boston, MA 02115 USA. [Boros, Laszlo] Univ Calif Los Angeles, UCLA Sch Med, Los Angeles, CA USA. [Boros, Laszlo] SiDMAP LLC, Los Angeles, CA USA. RP Girnun, GD (reprint author), Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Dept Biochem & Mol Biol, 655 W Baltimore St,BRB Room 10-039, Baltimore, MD 21201 USA. EM ggirnun@som.umaryland.edu FU University of Maryland Greenebaum Cancer Center CRF; Susan G. Komen Breast Cancer Foundation [KG081400]; NIDDK [DK064685] FX This work was supported by the University of Maryland Greenebaum Cancer Center CRF, Susan G. Komen Breast Cancer Foundation (KG081400), and NIDDK (DK064685) to Geoffrey D. Girnun. NR 50 TC 55 Z9 57 U1 0 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2011 VL 71 IS 21 BP 6888 EP 6898 DI 10.1158/0008-5472.CAN-11-1011 PG 11 WC Oncology SC Oncology GA 842ML UT WOS:000296603500035 PM 21914785 ER PT J AU Rocha-Singh, KJ Novack, V Pencina, M D'Agostino, R Ansel, G Rosenfield, K Jaff, MR AF Rocha-Singh, Krishna J. Novack, Victor Pencina, Michael D'Agostino, Ralph Ansel, Gary Rosenfield, Kenneth Jaff, Michael R. TI Objective Performance Goals of Safety and Blood Pressure Efficacy For Clinical Trials of Renal Artery Bare Metal Stents in Hypertensive Patients with Atherosclerotic Renal Artery Stenosis SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE renal artery stenosis; bare metal stents; resistant hypertension ID ANGIOPLASTY; REVASCULARIZATION; INTERVENTIONS; PREVENTION; GUIDELINES; MANAGEMENT; COMMITTEE; GRADIENT; DISEASE AB Objective: To provide safety and performance goals for prospective single-arm trials of bare metal renal artery stenting in patients with resistant hypertension associated with high grade atherosclerotic renal artery stenosis. Background: To date, there have been no US Pre-Market Approval (PMA) bare metal renal stent device trials which have focused on improvement of blood pressure control as a primary effectiveness endpoint. Methods: Analysis of subject-level data from three large industry sponsored pre-market approval (PMA) trials was performed. Hypertensive patients (>= 155 mmHg) with a >= 50% atherosclerotic renal artery stenosis were included. Thirty day and 9-month systolic and diastolic blood pressure measurements, renal function and 9-month duplex ultrasound assessment of renal artery patency were analyzed. Results: Initial data analysis of 600 patients from the 3 PMA trials identified 286 patients who met inclusion criteria. The mean baseline systolic blood pressure was 177.8 +/- 19.3 mmHg with a mean 68.1% diameter renal artery stenosis. Nine months after successful stenting, the mean SBP was 156.7 +/- 24.1 mmHg; the 9 month restenosis rate was 14.4%. Conclusion: Based on the statistical modeling of these data and a priori established performance criteria, the co-primary endpoints of 9 month reduction in blood pressure and in-stent restenosis are proposed. The reduction in blood pressure will be analyzed as a continuous variable and will be compared to this performance goal. (C) 2011 Wiley Periodicals, Inc. C1 [Rocha-Singh, Krishna J.] Prairie Educ & Res Cooperat, Springfield, IL 62794 USA. [Novack, Victor; Pencina, Michael; D'Agostino, Ralph] Harvard Clin Res Inst, Boston, MA 02115 USA. [Ansel, Gary] Riverside Hosp, Dept Cardiol, Columbus, OH USA. [Rosenfield, Kenneth] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Dept Vasc Med, Boston, MA 02114 USA. RP Rocha-Singh, KJ (reprint author), Prairie Educ & Res Cooperat, POB 19420, Springfield, IL 62794 USA. EM ksingh@prairieheart.com FU Abbott Vascular; Bard; Boston Scientific Corporation; Baxter; Atrium Medical, Inc; Invatec FX Dr. Krishna Rocha-Singh is a paid consultant for Medtronic, ev3 and Minnow Medical and is salaried as the Medical Director of Prairie Education and Research Cooperative and as a Board Member of VIVA Physicians. Dr. Michal Jaff is a non-compensated consultant for Abbott Vascular Devices, Boston Scientific Corporation., Covidien and Medtronic, a compensated consultant for Harvard Clinical Research Institute and Nexeon Medical Systems, and is a salaried Board Member of VIVA Physicians. Dr. Gary Ansel is a paid consultant for Cordis Corporation, Atrium Medical, Inc., Boston Scientific Corporation, Cook, Inc. and Abbott Vascular Devices, and is a salaried Board Member of VIVA Physicians. Dr. Kenneth Rosen-field is a paid consultant and Scientific Advisory Board Member for Abbott Vascular Devices, Harvard Clinical Research Institute, Lumen and Complete Conference Management, has received research or fellowship support from Abbott Vascular, Bard, Boston Scientific Corporation, Baxter, Atrium Medical, Inc. and Invatec, has equity in Lumen Biomedical, Medical Simulation Corporation and Primacea, and is a salaried Board Member of Viva Physicians. Drs. Victor Novack, Michael Pencina and Ralph D'Agostino have nothing to disclose. NR 28 TC 7 Z9 7 U1 0 U2 4 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 NOV 1 PY 2011 VL 78 IS 5 BP 779 EP 789 DI 10.1002/ccd.23055 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 840BI UT WOS:000296412800022 PM 21648052 ER PT J AU Forster, N Ellisen, LW AF Forster, Nicole Ellisen, Leif W. TI Notch signaling mediates p63-induced quiescence: A new facet of p63/Notch crosstalk SO CELL CYCLE LA English DT News Item ID P63; CELLS; ROLES; LIMB C1 [Forster, Nicole] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Forster, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM ellisen@helix.mgh.harvard.edu FU NIDCR NIH HHS [R01 DE015945] NR 9 TC 4 Z9 5 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV 1 PY 2011 VL 10 IS 21 BP 3632 EP 3633 DI 10.4161/cc.10.21.18182 PG 2 WC Cell Biology SC Cell Biology GA 842DZ UT WOS:000296572100014 PM 22041817 ER PT J AU Ferretti, R Sbroggio, M Di Savino, A Fusella, F Bertero, A Michowski, W Tarone, G Brancaccio, M AF Ferretti, Roberta Sbroggio, Mauro Di Savino, Augusta Fusella, Federica Bertero, Alessandro Michowski, Wojciech Tarone, Guido Brancaccio, Mara TI Morgana and Melusin Two fairies chaperoning signal transduction SO CELL CYCLE LA English DT Article DE Morgana; Melusin; ROCK; ERK1/2; genomic stability; centrosome duplication; heart hypertrophy ID HSP90 MOLECULAR CHAPERONE; CENTROSOME DUPLICATION; DISEASE RESISTANCE; PRESSURE-OVERLOAD; ESSENTIAL COMPONENT; CONTAINING PROTEIN; ROCK-II; SGT1; IQGAP1; RAR1 AB Chaperones and scaffold proteins are key elements involved in controlling the assembly of molecular complexes required for coordinated signal transduction. Here we describe morgana and melusin, two phylogenetically conserved chaperones that cooperate with Hsp90 and regulate signal transduction in important physiopathological processes. While morgana is ubiquitously expressed, melusin expression is restricted to striated muscles. Despite high sequence homology, the two chaperones have distinct functions. Morgana controls genomic stability by regulating the centrosome cycle via ROCKII kinase. Melusin, on the other hand, organizes ERK signal transduction in cardiomyocytes and regulates cardiac compensatory hypertrophy in response to different stress stimuli. C1 [Ferretti, Roberta; Sbroggio, Mauro; Di Savino, Augusta; Fusella, Federica; Bertero, Alessandro; Tarone, Guido; Brancaccio, Mara] Univ Turin, Ctr Mol Biotechnol, Dipartimento Genet Biol & Biochim, Turin, Italy. [Michowski, Wojciech] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Brancaccio, M (reprint author), Univ Turin, Ctr Mol Biotechnol, Dipartimento Genet Biol & Biochim, Turin, Italy. EM mara.brancaccio@unito.it OI Tarone, Guido/0000-0003-4805-086X FU EUGeneHeart [LSHM-CT-2005-018833]; Regione Piemonte POR F.E.S.R.; Associazione Italiana per la Ricerca sul Cancro FX We wish to thank R. Srinivasan for critical comments on the manuscript. This work was supported by grants from EUGeneHeart (LSHM-CT-2005-018833 to G T.), Regione Piemonte POR F.E.S.R. 2007/2013 "DRUIDI: Piattaforme Innovative per le Scienze della Vita" to G.T. and M.B. Regione Piemonte CIPE 2006 to M.B., Fondazione Veronesi to G.T., AIRC 2008 to M.B. and Foundation for Polish Science to W.M. NR 41 TC 12 Z9 12 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV 1 PY 2011 VL 10 IS 21 BP 3678 EP 3683 PG 6 WC Cell Biology SC Cell Biology GA 842DZ UT WOS:000296572100021 PM 22037254 ER PT J AU Harris, KM Strauss, CE Eagle, KA Hirsch, AT Isselbacher, EM Tsai, TT Shiran, H Fattori, R Evangelista, A Cooper, JV Montgomery, DG Froehlich, JB Nienaber, CA AF Harris, Kevin M. Strauss, Craig E. Eagle, Kim A. Hirsch, Alan T. Isselbacher, Eric M. Tsai, Thomas T. Shiran, Hadas Fattori, Rossella Evangelista, Arturo Cooper, Jeanna V. Montgomery, Daniel G. Froehlich, James B. Nienaber, Christoph A. CA Int Registry Acute Aortic TI Correlates of Delayed Recognition and Treatment of Acute Type A Aortic Dissection The International Registry of Acute Aortic Dissection (IRAD) SO CIRCULATION LA English DT Article DE aorta; aortic; aneurysm; thoracic; diagnosis; imaging; surgery ID TRANSESOPHAGEAL ECHOCARDIOGRAPHY; INTRAMURAL HEMATOMA; COMPUTED-TOMOGRAPHY; FREQUENCY; ANEURYSM; OUTCOMES; EXPERIENCE; DIAGNOSIS; DISEASE AB Background-In acute aortic dissection, delays exist between presentation and diagnosis and, once diagnosed, definitive treatment. This study aimed to define the variables associated with these delays. Methods and Results-Acute aortic dissection patients enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and January 2007 were evaluated for factors contributing to delays in presentation to diagnosis and in diagnosis to surgery. Multiple linear regression was performed to determine relative delay time ratios (DTRs) for individual correlates. The median time from arrival at the emergency department to diagnosis was 4.3 hours (quartile 1-3, 1.5-24 hours; n = 894 patients) and from diagnosis to surgery was 4.3 hours (quartile 1-3, 2.4-24 hours; n = 751). Delays in acute aortic dissection diagnosis occurred in female patients; those with atypical symptoms that were not abrupt or did not include chest, back, or any pain; patients with an absence of pulse deficit or hypotension; or those who initially presented to a nontertiary care hospital (all P < 0.05). The largest relative DTRs were for fever (DTR = 5.11; P < 0.001) and transfer from nontertiary hospital (DTR = 3.34; P < 0.001). Delay in time from diagnosis to surgery was associated with a history of previous cardiac surgery, presentation without abrupt or any pain, and initial presentation to a nontertiary care hospital (all P < 0.001). The strongest factors associated with operative delay were prolonged time from presentation to diagnosis (DTR = 1.35; P < 0.001), race other than white (DTR = 2.25; P < 0.001), and history of coronary artery bypass surgery (DTR = 2.81; P < 0.001). Conclusions-Improved physician awareness of atypical presentations and prompt transport of acute aortic dissection patients could reduce crucial time variables. (Circulation. 2011; 124: 1911-1918.) C1 [Harris, Kevin M.; Strauss, Craig E.] Abbott NW Hosp, Minneapolis Heart Inst Fdn, Minneapolis, MN 55407 USA. [Strauss, Craig E.; Hirsch, Alan T.] Univ Minnesota, Div Cardiovasc, Minneapolis, MN 55455 USA. [Hirsch, Alan T.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Eagle, Kim A.; Shiran, Hadas; Cooper, Jeanna V.; Montgomery, Daniel G.; Froehlich, James B.] Univ Michigan, Ann Arbor, MI 48109 USA. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tsai, Thomas T.] Univ Colorado, Denver, CO 80202 USA. [Fattori, Rossella] Univ Hosp S Orsola, Bologna, Italy. [Evangelista, Arturo] Hosp Gen Univ Vall dHebron, Barcelona, Spain. [Nienaber, Christoph A.] Univ Rostock, Rostock, Germany. RP Harris, KM (reprint author), Abbott NW Hosp, Minneapolis Heart Inst Fdn, 920 E 28th St,Ste 300, Minneapolis, MN 55407 USA. EM kharris@mplsheart.com FU University of Michigan Health System; Varbedian Fund for Aortic Research; Hewlett Foundation; Mardigian Foundation; GORE, Inc.; Bristol Myers Squibb; Blue Cross/Blue Shield of Michigan; GORE; Pfizer; SanofiAventis; Varbedian Fund; National Institutes of Health National Heart, Lung, and Blood Institute; Robert Wood Johnson Foundation FX IRAD is supported by grants from the University of Michigan Health System, Varbedian Fund for Aortic Research, Hewlett Foundation, Mardigian Foundation, and GORE, Inc.; Dr Eagle has received grant/research support from Bristol Myers Squibb, Blue Cross/Blue Shield of Michigan, GORE, Hewlett Foundation, Mardigian Foundation, Pfizer, SanofiAventis, and Varbedian Fund and consultant fees from the National Institutes of Health National Heart, Lung, and Blood Institute, Pfizer, SanofiAventis, and Robert Wood Johnson Foundation. Dr Froehlich has consulted with Pfizer and Sanofi-aventis; served on the speakers' bureau for Pfizer, Sanofi-aventis, and Merck; and has contracted research with Blue Cross/Blue Shield of Michigan, Mardigian Foundation, and Fibromuscular Disease Society of America. Dr Nienaber has received grant/research support from Varbedian Fund, Hewlett Foundation, Mardigian Foundation, and GORE, Inc. The sponsors had no role in the design and conduct of the study; the collection, management, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript. NR 25 TC 46 Z9 49 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 1 PY 2011 VL 124 IS 18 BP 1911 EP U82 DI 10.1161/CIRCULATIONAHA.110.006320 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 842JB UT WOS:000296593800013 PM 21969019 ER PT J AU Reynolds, MR Magnuson, EA Lei, Y Leon, MB Smith, CR Svensson, LG Webb, JG Babaliaros, VC Bowers, BS Fearon, WF Herrmann, HC Kapadia, S Kodali, SK Makkar, RR Pichard, AD Cohen, DJ AF Reynolds, Matthew R. Magnuson, Elizabeth A. Lei, Yang Leon, Martin B. Smith, Craig R. Svensson, Lars G. Webb, John G. Babaliaros, Vasilis C. Bowers, Bruce S. Fearon, William F. Herrmann, Howard C. Kapadia, Samir Kodali, Susheel K. Makkar, Raj R. Pichard, Augusto D. Cohen, David J. CA Placement Aortic Transcatheter TI Health-Related Quality of Life After Transcatheter Aortic Valve Replacement in Inoperable Patients With Severe Aortic Stenosis SO CIRCULATION LA English DT Article DE aortic valve stenosis; heart valves; quality of life ID ACUTE MYOCARDIAL-INFARCTION; HEART-FAILURE; GREATER-THAN-80 YEARS; ELDERLY-PATIENTS; IMPLANTATION; SURVIVAL; OUTCOMES; SURGERY; RISK; EFFICACY AB Background-Transcatheter aortic valve replacement (TAVR) has been shown to improve survival compared with standard therapy in patients with severe aortic stenosis who cannot have surgery. The effects of TAVR on health-related quality of life have not been reported from a controlled study. Methods and Results-The Placement of Aortic Transcatheter Valves (PARTNER) trial randomized patients with symptomatic, severe aortic stenosis who were not candidates for surgical valve replacement to TAVR (n = 179) or standard therapy (n = 179). Health-related quality of life was assessed at baseline and at 1, 6, and 12 months with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the 12-item Short Form-12 General Health Survey (SF-12). The primary end point was the KCCQ overall summary score (range, 0-100; higher = better). At baseline, mean KCCQ summary scores (35 +/- 20) and SF-12 physical summary scores (28 +/- 7) were markedly depressed. Although the KCCQ summary score improved from baseline in both groups, the extent of improvement was greater after TAVR compared with control at 1 month (mean between-group difference, 13 points; 95% confidence interval, 8-19; P < 0.001) with larger benefits at 6 months (mean difference, 21 points; 95% confidence interval, 15-27; P < 0.001) and 12 months (mean difference, 26 points; 95% confidence interval, 19-33; P < 0.001). At 12 months, TAVR patients also reported higher SF-12 physical and mental health scores with mean differences compared with standard care of 5.7 and 6.4 points, respectively (P < 0.001 for both comparisons). Conclusions-Among inoperable patients with severe aortic stenosis, compared with standard care, TAVR resulted in significant improvements in health-related quality of life that were maintained for at least 1 year. C1 [Cohen, David J.] Univ Missouri Kansas City, Sch Med, St Lukes Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Reynolds, Matthew R.] Boston VA Healthcare Syst, Harvard Clin Res Inst, Boston, MA USA. [Leon, Martin B.; Smith, Craig R.; Kodali, Susheel K.] Columbia Presbyterian Med Ctr, New York, NY USA. [Svensson, Lars G.; Kapadia, Samir] Cleveland Clin, Cleveland, OH 44106 USA. [Webb, John G.] St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. [Babaliaros, Vasilis C.] Emory Univ Hosp, Atlanta, GA 30322 USA. [Bowers, Bruce S.] Med City Dallas, Dallas, TX USA. [Fearon, William F.] Stanford Univ, Stanford, CA 94305 USA. [Herrmann, Howard C.] Univ Penn, Philadelphia, PA 19104 USA. [Makkar, Raj R.] Cedars Sinai Heart Inst, Los Angeles, CA USA. [Pichard, Augusto D.] Washington Hosp Ctr, Washington, DC 20010 USA. [Magnuson, Elizabeth A.; Lei, Yang; Cohen, David J.] Univ Missouri Kansas City, St Lukes Mid Amer Heart & Vasc Inst, Kansas City, MO 64111 USA. RP Cohen, DJ (reprint author), Univ Missouri Kansas City, Sch Med, St Lukes Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM dcohen@saint-lukes.org FU Edwards Lifesciences, Inc.; Edwards Lifesciences; Biosense Webster; Sanofi-aventis; St. Jude Medical; Eli Lilly; Daiichi Sankyo; Bristol-Myers Squibb; Medtronic; Embrella Cardiovascular; Guided Delivery Systems; Siemens; Philips; Valtech Cardio; Cordis; Lilly Pharmaceuticals; Daiichi-Sanyo Pharmaceuticals; Abbott Vascular; Access Closure; National Institutes of Health; Tryton Medical; Gore; Johnson Johnson; Boston Scientific; Merck; Astra-Zeneca; theHeart.org.; Lilly; MedRad; Merck/Schering-Plough; Eli Lilly-Daiichi Sankyo FX This work was supported by Edwards Lifesciences, Inc. (http://www.clinicaltrials.gov; unique identifier: NCT00530894).; Dr Reynolds has received research support from Edwards Lifesciences, Biosense Webster, and Sanofi-aventis and consulting income from Biosense Webster, Sanofi-aventis, and St. Jude Medical. Dr Magnuson has received grant support from Eli Lilly, Daiichi Sankyo, Sanofi-aventis, and Bristol-Myers Squibb. Dr Leon has received consulting fees from Medtronic and has stock options in Sadra Medical. Dr Webb has received research support from Edwards Lifesciences, Embrella Cardiovascular, Guided Delivery Systems, and Siemens and consulting income from Edwards Lifesciences, Embrella Cardiovascular, Guided Delivery Systems, Philips, St. Jude Medical, Siemens, and Valtech Cardio. Dr Babaliaros has been a consultant for Symetis and Direct Flow Medical. Dr Bowers has received consulting fees or speaking honoraria from Cordis, St. Jude Medical, Lilly Pharmaceuticals, Daiichi-Sanyo Pharmaceuticals, Abbott Vascular, Medtronic, and Access Closure. Dr Fearon has received research support from the National Institutes of Health and St. Jude Medical and consulting fees from Tryton Medical. Dr Herrmann has received research support from Edwards Lifesciences, Abbott, St. Jude Medical, Gore, Johnson & Johnson, Boston Scientific, and Medtronic; speaking honoraria from Edwards Lifesciences and Schering Plough; and consulting fees from Gore, Merck, Astra-Zeneca; Dr Herrmann also has equity in Endovalve, Inc. Dr Kodali has received consulting income from Edwards Lifesciences, Medtronic, and theHeart.org. Dr Makkar has received consulting fees, grant support, and lectures fees from Abbott, Medtronic, and Lilly; consulting fees and grant support from Johnson & Johnson and Daiichi Sankyo; and grant support from St. Jude Medical and Edwards Lifesciences. Dr Pichard has received consulting income from Edwards Lifesciences and speaking honoraria from St. Jude Medical. Dr Cohen has received research support from Edwards Lifesciences, Medtronic, Boston Scientific, Abbott Vascular, MedRad, Merck/Schering-Plough, and Eli Lilly-Daiichi Sankyo; consulting income from Schering-Plough, Eli Lilly, Medtronic, and Cordis; and speaking honoraria from Eli Lilly, The Medicines Company, and St. Jude Medical. The other authors report no conflicts. NR 33 TC 147 Z9 154 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 1 PY 2011 VL 124 IS 18 BP 1964 EP 1972 DI 10.1161/CIRCULATIONAHA.111.040022 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 842JB UT WOS:000296593800019 PM 21969017 ER PT J AU Magnani, JW Rienstra, M Lin, H Sinner, MF Lubitz, SA McManus, DD Dupuis, J Ellinor, PT Benjamin, EJ AF Magnani, Jared W. Rienstra, Michiel Lin, Honghuang Sinner, Moritz F. Lubitz, Steven A. McManus, David D. Dupuis, Josee Ellinor, Patrick T. Benjamin, Emelia J. TI Atrial Fibrillation Current Knowledge and Future Directions in Epidemiology and Genomics SO CIRCULATION LA English DT Article DE atrial fibrillation; arrhythmias, cardiac; epidemiology; genetics; genomics; review; risk factors ID OF-FUNCTION MUTATION; CA2+-ACTIVATED K+ CHANNEL; CONGESTIVE-HEART-FAILURE; COMMUNITY-BASED COHORT; RISK-FACTORS; ATHEROSCLEROSIS RISK; FUNCTIONAL MODULES; AFRICAN-AMERICANS; SMALL-CONDUCTANCE; ISCHEMIC-STROKE C1 [Magnani, Jared W.] Boston Univ, Sch Med, Sect Cardiovasc Med, Dept Med, Boston, MA 02118 USA. [Magnani, Jared W.; Sinner, Moritz F.; Dupuis, Josee; Benjamin, Emelia J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Rienstra, Michiel] Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands. [Sinner, Moritz F.; Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Sinner, Moritz F.] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, Dept Med, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu OI Lin, Honghuang/0000-0003-3043-3942; Dupuis, Josee/0000-0003-2871-3603; Benjamin, Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X FU American Heart Association [09FTF 2190028]; Netherlands Organization for Scientific Research [825.09.020]; German Heart Foundation; National Institutes of Health (NIH) [R37HL69874-08, U01HL105268, HL092577, RO1AG028321, RC1-HL01056, 1R01HL102214, 5R21DA027021, 1RO1HL104156, 1K24HL105780]; [6R01-NS17950]; [N01-HC25195] FX Dr Magnani is supported by American Heart Association Award 09FTF 2190028. Dr Rienstra is supported by a grant from the Netherlands Organization for Scientific Research (Rubicon grant 825.09.020). Dr Sinner is supported by the German Heart Foundation. Dr McManus is supported by grants from the National Institutes of Health (NIH; R37HL69874-08, U01HL105268). This work was supported by grants from the NIH to Drs Benjamin and Ellinor (HL092577), Dr Benjamin (RO1AG028321, RC1-HL01056, 1R01HL102214), and Dr Ellinor (5R21DA027021, 1RO1HL104156, 1K24HL105780) and by 6R01-NS17950 and N01-HC25195. NR 147 TC 102 Z9 106 U1 1 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 1 PY 2011 VL 124 IS 18 BP 1982 EP U170 DI 10.1161/CIRCULATIONAHA.111.039677 PG 16 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 842JB UT WOS:000296593800021 PM 22042927 ER PT J AU Lee, BY Song, Y McGlone, SM Bailey, RR Feura, JM Tai, JHY Lewis, GJ Wiringa, AE Smith, KJ Muder, RR Harrison, LH Piraino, B AF Lee, B. Y. Song, Y. McGlone, S. M. Bailey, R. R. Feura, J. M. Tai, J. H. Y. Lewis, G. J. Wiringa, A. E. Smith, K. J. Muder, R. R. Harrison, L. H. Piraino, B. TI The economic value of screening haemodialysis patients for methicillin-resistant Staphylococcus aureus in the USA SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article DE Cost-effectiveness; economics; haemodialysis; methicillin-resistant Staphylococcus aureus; surveillance ID HEALTH-CARE WORKERS; DIALYSIS PATIENTS; SURGERY PATIENTS; UNITED-STATES; MUPIROCIN; COLONIZATION; INFECTIONS; PREVALENCE; CARRIAGE; CALCIUM AB Methicillin-resistant Staphylococcus aureus (MRSA) can cause severe infections in patients undergoing haemodialysis. Routine periodic testing of haemodialysis patients and attempting to decolonize those who test positive may be a strategy to prevent MRSA infections. The economic value of such a strategy has not yet been estimated. We constructed a Markov computer simulation model to evaluate the economic value of employing routine testing (agar-based or PCR) at different MRSA prevalence, spontaneous clearance, costs of decolonization and decolonization success rates, performed every 3, 6 or 12 months. The model showed periodic MRSA surveillance with either test to be cost-effective (incremental cost-effectiveness ratio <=$50 000/quality-adjusted life-year) for all conditions tested. Agar surveillance was dominant (i.e. less costly and more effective) at an MRSA prevalence >= 10% and a decolonization success rate >= 25% for all decolonization treatment costs tested with no spontaneous clearance. PCR surveillance was dominant when the MRSA prevalence was >= 20% and decolonization success rate was >= 75% with no spontaneous clearance. Routine periodic testing and decolonization of haemodialysis patients for MRSA may be a cost-effective strategy over a wide range of MRSA prevalences, decolonization success rates, and testing intervals. C1 [Lee, B. Y.; Song, Y.; McGlone, S. M.; Bailey, R. R.; Feura, J. M.; Tai, J. H. Y.; Lewis, G. J.; Wiringa, A. E.] Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR, Pittsburgh, PA 15213 USA. [Lee, B. Y.; Song, Y.; McGlone, S. M.; Bailey, R. R.; Feura, J. M.; Tai, J. H. Y.; Lewis, G. J.; Wiringa, A. E.] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15213 USA. [Lee, B. Y.; Song, Y.; McGlone, S. M.; Bailey, R. R.; Feura, J. M.; Tai, J. H. Y.; Lewis, G. J.; Wiringa, A. E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Smith, K. J.] Univ Pittsburgh, Sect Decis Sci & Clin Syst Modeling, Pittsburgh, PA 15213 USA. [Muder, R. R.] Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Div Infect Dis, Pittsburgh, PA 15213 USA. [Harrison, L. H.] Univ Pittsburgh, Sch Med, Infect Dis Epidemiol Res Unit, Pittsburgh, PA 15213 USA. [Piraino, B.] Univ Pittsburgh, Div Nephrol, Pittsburgh, PA 15213 USA. RP Lee, BY (reprint author), Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR, 200 Meyran Ave,Suite 200, Pittsburgh, PA 15213 USA. EM byl1@pitt.edu OI Piraino, Beth/0000-0001-5061-0841; Slayton, Rachel/0000-0003-4699-8040 FU National Institute of General Medical Sciences Models of Infectious Disease Agent Study (MIDAS) [5U54GM088491-02]; Pennsylvania Department of Health (DOH) [4100047864] FX This work was supported by the National Institute of General Medical Sciences Models of Infectious Disease Agent Study (MIDAS) grant 5U54GM088491-02 and the Pennsylvania Department of Health (DOH) grant 4100047864. The funders had no role in the design and conduct of the study, collection, management, analysis and interpretation of the data, or preparation, review or approval of the manuscript. NR 21 TC 11 Z9 11 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD NOV PY 2011 VL 17 IS 11 BP 1717 EP 1726 DI 10.1111/j.1469-0691.2011.03525.x PG 10 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 846PS UT WOS:000296916300026 PM 21595796 ER PT J AU Cheng, CE Kroshinsky, D AF Cheng, Carol E. Kroshinsky, Daniela TI Iatrogenic skin injury in hospitalized patients SO CLINICS IN DERMATOLOGY LA English DT Article ID TOXIC EPIDERMAL NECROLYSIS; ALLERGIC CONTACT-DERMATITIS; GENERALIZED EXANTHEMATOUS PUSTULOSIS; STEVENS-JOHNSON-SYNDROME; INDUCED HYPERSENSITIVITY SYNDROME; LINEAR IGA DERMATOSIS; PYODERMA-GANGRENOSUM; SYSTEMIC SYMPTOMS; PRESSURE ULCERS; POVIDONE-IODINE AB Iatrogenic skin injuries in hospitalized patients range from drug-related complications to those related to procedures. Common drug complications include drug reaction with eosinophilia and systemic symptoms (DRESS), linear immunoglobulin (Ig) A bullous dermatosis, Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute generalized exanthematous pustulosis. Contact dermatitis can result from surgical preparations of chlorhexidine and povidone-iodine, medical adhesives, topical postsurgical ointments, most commonly neomycin and bacitracin, and internal prostheses, including coronary stents, pacemakers, and metal joints. Complications arising from procedures include thrombosis caused by placement of peripherally inserted central catheters, pyoderma gangrenosum from sites of dermal trauma, and anetoderma of prematurity from cutaneous monitoring devices in neonates. Calcinosis cutis and decubitus ulcers are also hospital problems. (C) 2011 Published by Elsevier Inc. C1 [Kroshinsky, Daniela] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. RP Kroshinsky, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, 50 Stanford St,Ste 200, Boston, MA 02114 USA. EM dkroshinsky@partners.org NR 77 TC 10 Z9 11 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0738-081X J9 CLIN DERMATOL JI Clin. Dermatol. PD NOV-DEC PY 2011 VL 29 IS 6 BP 622 EP 632 DI 10.1016/j.clindermatol.2011.08.006 PG 11 WC Dermatology SC Dermatology GA 842MB UT WOS:000296602500005 PM 22014984 ER PT J AU Adler, LA Shaw, DM Spencer, TJ Newcorn, JH Sitt, DJ Morrill, M Davidow, JV Glatt, SJ Faraone, SV AF Adler, Lenard A. Shaw, David M. Spencer, Thomas J. Newcorn, Jeffrey H. Sitt, David J. Morrill, Melinda Davidow, Jennifer V. Glatt, Stephen J. Faraone, Stephen V. TI Reliability and validity of the Time-Sensitive ADHD Symptom Scale in adults SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DOUBLE-BLIND; EXTENDED-RELEASE; EFFICACY; SAFETY; TRIAL; VALIDATION AB Objectives: The objective of this study was to examine the psychometric properties of the Time-Sensitive A DHD Symptom Scale (TASS) to evaluate change of attention-deficit/hyperactivity disorder (ADHD) symptoms over the course of a day in adults. Methods: Eighty adults with ADHD participated in 1 or 2 visits, 1 to 9 weeks apart. At each visit, participants completed the TASS followed by raters administering the ADHD Rating Scale (ADHD-RS). Additional TASS and ADHD-RS ratings were completed 2 to 6 hours after each visit via telephone. Internal consistency of TASS items was assessed by Cronbach's alpha. Convergent validity of TASS and ADHD-RS total mean item scores was assessed using Pearson's correlation coefficients. kappa correlations were calculated to assess item-by-item reliability between TASS and ADHD-RS items. Results: Internal consistency of TASS items was high, with an overall Cronbach's alpha coefficient of .93. The Pearson's correlation coefficient between the TASS and ADHD-RS was significant for all visits (r = 0.70, P < .0001). There was moderate agreement between individual items on the TASS and ADHD-RS, with significant kappa coefficients for almost all items (P < .05). Discussion: The TASS showed high internal consistency and concurrent validity with the clinician-administered ADHD-RS and is a valid and reliable scale for measuring change in ADHD symptoms over the course of a day in adults. Published by Elsevier Inc. C1 [Adler, Lenard A.; Shaw, David M.] NYU, Sch Med, Dept Psychiat, New York, NY 10010 USA. [Adler, Lenard A.] NYU, Sch Med, Dept Child & Adolescent Psychiat, New York, NY 10010 USA. [Adler, Lenard A.] VA NY Harbor Healthcare Syst, Psychiat Serv, New York, NY 10016 USA. [Spencer, Thomas J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. [Spencer, Thomas J.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA USA. [Newcorn, Jeffrey H.; Davidow, Jennifer V.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Sitt, David J.] Baruch Coll, Dept Psychol, New York, NY 10010 USA. [Morrill, Melinda] Clark Univ, Dept Psychol, Worcester, MA 01610 USA. [Glatt, Stephen J.; Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Glatt, Stephen J.; Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. RP Adler, LA (reprint author), NYU, Sch Med, New York, NY 10016 USA. EM lenard.adler@nyumc.org OI Glatt, Stephen/0000-0002-0360-7567; Newcorn, Jeffrey /0000-0001-8993-9337; Adler, Len/0000-0002-9812-8234; Faraone, Stephen/0000-0002-9217-3982 FU Shire Development, Inc. FX This study was supported in part by an investigator-initiated research grant from Shire Development, Inc. NR 30 TC 6 Z9 6 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 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD NOV-DEC PY 2011 VL 52 IS 6 BP 769 EP 773 DI 10.1016/j.comppsych.2010.12.002 PG 5 WC Psychiatry SC Psychiatry GA 840WF UT WOS:000296471800028 PM 21306705 ER PT J AU Miles, WO Dyson, NJ Walker, JA AF Miles, Wayne O. Dyson, Nicholas J. Walker, James A. TI Modeling tumor invasion and metastasis in Drosophila SO DISEASE MODELS & MECHANISMS LA English DT Article ID SRC FAMILY KINASES; CELL POLARITY; TRANSCRIPTIONAL REPRESSOR; MOLECULAR-CLONING; ONCOGENIC RAS; HUMAN CANCER; GROWTH; MELANOGASTER; PROTEIN; SUPPRESSOR AB Conservation of major signaling pathways between humans and flies has made Drosophila a useful model organism for cancer research. Our understanding of the mechanisms regulating cell growth, differentiation and development has been considerably advanced by studies in Drosophila. Several recent high profile studies have examined the processes constraining the metastatic growth of tumor cells in fruit fly models. Cell invasion can be studied in the context of an in vivo setting in flies, enabling the genetic requirements of the microenvironment of tumor cells undergoing metastasis to be analyzed. This Perspective discusses the strengths and limitations of Drosophila models of cancer invasion and the unique tools that have enabled these studies. It also highlights several recent reports that together make a strong case for Drosophila as a system with the potential for both testing novel concepts in tumor progression and cell invasion, and for uncovering players in metastasis. C1 [Miles, Wayne O.; Dyson, Nicholas J.; Walker, James A.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Miles, Wayne O.; Dyson, Nicholas J.; Walker, James A.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Walker, James A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Walker, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, 149 13th St, Charlestown, MA 02129 USA. EM jwalker@helix.mgh.harvard.edu FU National Institutes of Health (NIH) [R01GM53202]; Department of Defense (DOD) [W81XWH-09-1-0487] FX Work in the authors' laboratories is supported by the National Institutes of Health (NIH) [R01GM53202] to N.J.D.; and the Department of Defense (DOD) [W81XWH-09-1-0487] to J.A.W. NR 68 TC 31 Z9 32 U1 0 U2 20 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 NOV PY 2011 VL 4 IS 6 BP 753 EP 761 DI 10.1242/dmm.006908 PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 844QD UT WOS:000296761500008 PM 21979943 ER PT J AU Fredericks, WJ McGarvey, T Wang, HY Lal, P Puthiyaveettil, R Tomaszewski, J Sepulveda, J Labelle, E Weiss, JS Nickerson, ML Kruth, HS Brandt, W Wessjohann, LA Malkowicz, SB AF Fredericks, William J. McGarvey, Terry Wang, Huiyi Lal, Priti Puthiyaveettil, Raghunath Tomaszewski, John Sepulveda, Jorge Labelle, Ed Weiss, Jayne S. Nickerson, Michael L. Kruth, Howard S. Brandt, Wolfgang Wessjohann, Ludger A. Malkowicz, S. Bruce TI The Bladder Tumor Suppressor Protein TERE1 (UBIAD1) Modulates Cell Cholesterol: Implications for Tumor Progression SO DNA AND CELL BIOLOGY LA English DT Article ID PROSTATE-CANCER CELLS; VITAMIN-K; APOLIPOPROTEIN-E; CARCINOMA-CELLS; CORNEAL-DYSTROPHY; OXIDATIVE STRESS; MITOCHONDRIAL CHOLESTEROL; HEPATOCELLULAR-CARCINOMA; XENOBIOTIC RECEPTOR; MACROPHAGE ABCA1 AB Convergent evidence implicates the TERE1 protein in human bladder tumor progression and lipid metabolism. Previously, reduced TERE1 expression was found in invasive urologic cancers and inhibited cell growth upon re-expression. A role in lipid metabolism was suggested by TERE1 binding to APOE, a cholesterol carrier, and to TBL2, a candidate protein in triglyceride disorders. Natural TERE1 mutations associate with Schnyder's corneal dystrophy, characterized by lipid accumulation. TERE1 catalyzes menaquinone synthesis, known to affect cholesterol homeostasis. To explore this relationship, we altered TERE1 and TBL2 dosage via ectopic expression and interfering RNA and measured cholesterol by Amplex red. Protein interactions of wild-type and mutant TERE1 with GST-APOE were evaluated by binding assays and molecular modeling. We conducted a bladder tumor microarray TERE1 expression analysis and assayed tumorigenicity of J82 cells ectopically expressing TERE1. TERE1 expression was reduced in a third of invasive specimens. Ectopic TERE1 expression in J82 bladder cancer cells dramatically inhibited nude mouse tumorigenesis. TERE1 and TBL2 proteins inversely modulated cellular cholesterol in HEK293 and bladder cancer cells from 20% to 50%. TERE1 point mutations affected APOE interactions, and resulted in cholesterol levels that differed from wild type. Elevated tumor cell cholesterol is known to affect apoptosis and growth signaling; thus, loss of TERE1 in invasive bladder cancer may represent a defect in menaquinone-mediated cholesterol homeostasis that contributes to progression. C1 [Fredericks, William J.] Univ Penn, Dept Surg, Div Urol, VAMC Philadelphia, Philadelphia, PA 19104 USA. [McGarvey, Terry] Kirksville Osteopath Med Sch, Dept Anat, Kirksville, MO USA. [Lal, Priti; Puthiyaveettil, Raghunath; Tomaszewski, John; Sepulveda, Jorge] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Malkowicz, S. Bruce] Vet Affairs Med Ctr, Dept Surg Urol & Pathol, Philadelphia, PA USA. [Sepulveda, Jorge] Vet Affairs Med Ctr, Pathol Serv, Philadelphia, PA USA. [Labelle, Ed] Gloucester Cty Coll, Sewell, NJ USA. [Weiss, Jayne S.] Louisiana State Univ, Dept Ophthalmol, New Orleans, LA USA. [Weiss, Jayne S.] Louisiana State Univ, Ctr Eye, New Orleans, LA 70112 USA. [Nickerson, Michael L.] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. [Kruth, Howard S.] NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. [Brandt, Wolfgang; Wessjohann, Ludger A.] Leibniz Inst Plant Biochem, Halle, Germany. RP Fredericks, WJ (reprint author), Univ Penn, Dept Surg, Div Urol, VAMC Philadelphia, Univ & Woodland Ave,Room A418, Philadelphia, PA 19104 USA. EM william.fredericks@uphs.upenn.edu FU Veterans Affairs Merit Review; Veterans Affairs Medical Center Philadelphia FX We thank the Veterans Affairs Merit Review and the Veterans Affairs Medical Center Philadelphia for the grant support to S.B. Malkowicz. We thank the Innisfree Foundation of Bryn Mawr, PA, and The Castleman Family Fund for their generous support to S.B. Malkowicz and W.J. Fredericks. NR 92 TC 21 Z9 21 U1 1 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD NOV PY 2011 VL 30 IS 11 BP 851 EP 864 DI 10.1089/dna.2011.1315 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 843GW UT WOS:000296661300001 PM 21740188 ER PT J AU Stengel, A Tache, Y AF Stengel, Andreas Tache, Yvette TI Minireview: Nesfatin-1-An Emerging New Player in the Brain-Gut, Endocrine, and Metabolic Axis SO ENDOCRINOLOGY LA English DT Review ID SATIETY MOLECULE NESFATIN-1; PITUITARY-ADRENAL AXIS; CENTRAL-NERVOUS-SYSTEM; FOOD-INTAKE; PARAVENTRICULAR NUCLEUS; ARCUATE NUCLEUS; RAT-BRAIN; NEURONS; IMMUNOREACTIVITY; HYPOTHALAMUS AB Nesfatin-1 is a recently identified 82-amino-acid peptide derived from the precursor protein, nucleobindin2 (NUCB2). The brain distribution of NUCB2/nesfatin-1 at the mRNA and protein level along with functional studies in rodents support a role for NUCB2/nesfatin-1 as a novel satiety molecule acting through leptin-independent mechanisms. In addition, nesfatin-1 induces a wide spectrum of central actions to stimulate the pituitary-adrenal axis and sympathetic nervous system and influences visceral functions and emotion. These central actions combined with the activation of NUCB2/nesfatin-1 neurons in the brain by various stressors are indicative of a role in the adaptive response under stressful conditions. In the periphery, evidence is mounting that nesfatin-1 exerts a direct glucose-dependent insulinotropic action on beta-cells of the pancreatic islets. However, the cellular mechanisms of nesfatin-1's action remain poorly understood, partly because the receptor through which nesfatin-1 exerts its pleiotropic actions is yet to be identified. (Endocrinology 152: 4033-4038, 2011) C1 [Tache, Yvette] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Neurobiol Stress, Los Angeles, CA 90073 USA. [Stengel, Andreas; Tache, Yvette] Univ Calif Los Angeles, Dept Med, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress,Digest Dis Div, Los Angeles, CA 90024 USA. [Stengel, Andreas] Univ Med Berlin, Charite, Div Psychosomat Med & Psychotherapy, Dept Med, D-10117 Berlin, Germany. RP Tache, Y (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Neurobiol Stress, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU National Institutes of Health (NIH) [R01 DK-33061]; NIH Center [DK-41301 (Animal Core)]; Veterans Affairs Research Career Scientist grant FX This work was supported by National Institutes of Health (NIH) R01 DK-33061, NIH Center Grant DK-41301 (Animal Core), and a Veterans Affairs Research Career Scientist grant (to Y.T.). NR 58 TC 41 Z9 43 U1 2 U2 12 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 NOV PY 2011 VL 152 IS 11 BP 4033 EP 4038 DI 10.1210/en.2011-1500 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 842GR UT WOS:000296583900007 PM 21862618 ER PT J AU Ahmed, AA Pineda, R AF Ahmed, Abdalla Awadalla Pineda, Roberto TI Alcaligenes xylosoxidans Contact Lens-Related Keratitis-A Case Report and Literature Review SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Review DE Alcaligenes xylosoxidans; Infectious keratitis; Contact lens ID ACHROMOBACTER-XYLOSOXIDANS; CORNEAL ULCER; ENDOPHTHALMITIS AB Background: Alcaligenes xylosoxidans can result in opportunistic infections in patients who are immunocompromised. Alcaligenes xylosoxidans keratitis is a rare infection, almost always occurring in a compromised cornea. Few reported cases have occurred as contact lens-induced keratitis. The purposes of this report are to report a case of A. xylosoxidans keratitis in an immunocompetent contact lens wearer (2-week disposable) and to review the related literature. Methods: A 30-year-old man developed acute keratitis in the right eye. He was a 2-week disposable contact lens wearer. He did not report any ocular or systemic illness. Corneal scraping, contact lens, and conjunctiva cultures were performed. Results: 0.5% moxifloxacin eye drops were started hourly with quick recovery and healing of the ulcer and epithelial defect noted within a few days. Culture of the contact lens was positive for A. xylosoxidans. The organism was sensitive to penicillins, third-generation cephalosporins, and fluoroquinolones but resistant to aminoglycosides. Conclusions: Alcaligenes xylosoxidans is a potential pathogen in compromised corneas. It has high susceptibility to extended-spectrum penicillins and current generations of fluoroquinolones but rarely responds to aminoglycosides. Alcaligenes xylosoxidans should be considered in the differential diagnosis of contact lens-induced keratitis. C1 [Pineda, Roberto] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Ahmed, Abdalla Awadalla] Makkah Eye Complex, Khartoum, Sudan. RP Ahmed, AA (reprint author), Makkah Eye Complex, POB 12368, Khartoum, Sudan. EM Abdu1974@hotmail.com NR 25 TC 3 Z9 3 U1 0 U2 1 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 NOV PY 2011 VL 37 IS 6 BP 386 EP 389 DI 10.1097/ICL.0b013e318235893a PG 4 WC Ophthalmology SC Ophthalmology GA 841QS UT WOS:000296528100013 PM 21993586 ER PT J AU Kakarala, K Faquin, WC Deschler, DG AF Kakarala, Kiran Faquin, William C. Deschler, Daniel G. TI EFFECT OF GLOSSECTOMY TECHNIQUE ON HISTOPATHOLOGIC ASSESSMENT IN A RAT MODEL SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article; Proceedings Paper CT Combined Section Meeting of the Triological-Society CY FEB 04-07, 2010 CL Orlando, FL SP Triol Soc DE head and neck; glossectomy; histopathology; margin; ultrasonic ID ULTRASONIC SCALPEL; SQUAMOUS CARCINOMA; SURGICAL-TREATMENT; ORAL-MUCOSA; TONGUE; ELECTROSURGERY; MONOPOLAR; CO2-LASER; CANCER; NECK AB Background. The purpose of this study was to compare the tissue effects of 3 surgical methods of glossectomy with respect to histopathologic assessment by a pathologist. Methods. The anterior tongue of 30 Sprague-Dawley rats was excised using either a steel scalpel, monopolar electrosurgery, or ultrasonic scalpel (3 groups of 10). Specimens were examined by a pathologist blinded to the surgical procedure, using a previously described grading system for margin artifact assessment. Results. Minimal tissue disruption at the surgical margin was produced by the steel scalpel, in contrast to monopolar electrosurgery and ultrasonic scalpel, which both produced varying levels of tissue distortion. Margin fragmentation was significantly greater with monopolar electrosurgery when compared to an ultrasonic scalpel. Conclusion. Ultrasonic scalpel creates less tissue distortion at the surgical margin than monopolar electrosurgery. Further study is required to determine the clinical relevance of these findings. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 1576-1580, 2011 C1 [Kakarala, Kiran; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Head & Neck Surg, Boston, MA 02114 USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kakarala, Kiran; Deschler, Daniel G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM daniel_deschler@meei.harvard.edu OI Kakarala, Kiran/0000-0002-1003-8024 NR 13 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD NOV PY 2011 VL 33 IS 11 BP 1576 EP 1580 DI 10.1002/hed.21632 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 840GH UT WOS:000296426700006 PM 21990222 ER PT J AU Silver, AL Farkash, EA Pitman, MB Rocco, JW AF Silver, Amanda L. Farkash, Evan A. Pitman, Martha B. Rocco, James W. TI ROSAI-DORFMAN DISEASE PRESENTING IN THE OROPHARYNX SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article ID SINUS HISTIOCYTOSIS; SPECTRUM; HEAD; NECK AB Background. We report a case of Rosai-Dorfman disease (RDD) presenting as an oropharyngeal mass, and we provide a detailed discussion of this rare clinical entity. Methods. An initial biopsy, described as being consistent with lymphoma, was reviewed at a second outside institution and was thought to be reactive lymphoid hyperplasia. The patient then presented to our institution for a second opinion. Direct laryngoscopy revealed a firm 1- to 2-cm lesion involving the left soft palate and superior tonsillar pillar. Results. The diagnosis of RDD was confirmed with immunohistochemical staining on both cytology and histology. The patient elected conservative management and has remained asymptomatic for over 15 months. Conclusion. The diagnosis of RDD may be challenging in cases presenting initially with extranodal disease. Close follow-up and repeat biopsies may be necessary. Identification of Rosai-Dorfman cells with emperipolesis and confirmation with appropriate immunohistochemical staining on both cytology and histology is diagnostic of RDD. Conservative treatment is appropriate in select cases. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 1660-1663, 2011 C1 [Silver, Amanda L.; Rocco, James W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Head & Neck Surg, Boston, MA 02114 USA. [Farkash, Evan A.; Pitman, Martha B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Rocco, James W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Rocco, James W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Rocco, JW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM jrocco@partners.org NR 10 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD NOV PY 2011 VL 33 IS 11 BP 1660 EP 1663 DI 10.1002/hed.21446 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 840GH UT WOS:000296426700017 PM 20544818 ER PT J AU Rothers, J Wright, AL Stern, DA Halonen, M Camargo, CA AF Rothers, Janet Wright, Anne L. Stern, Debra A. Halonen, Marilyn Camargo, Carlos A., Jr. TI Cord blood 25-hydroxyvitamin D levels are associated with aeroallergen sensitization in children from Tucson, Arizona SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Vitamin D; IgE; aeroallergen; allergic rhinitis; asthma; children ID VITAMIN-D INTAKE; CHILDHOOD ASTHMA; ALLERGIC RHINITIS; D SUPPLEMENTATION; PREGNANCY; DISEASES; RISK; IGE; DEFICIENCY; INFANTS AB Background: The association between vitamin D status at birth and childhood allergic outcomes is uncertain. The desert climate of Tucson offers a unique setting for studying the health effects of higher exposure to vitamin D. Objective: To assess the relationship between cord blood 25-hydroxyvitamin D (25[OH]D) levels and allergic outcomes through age 5 years. Methods: Cord blood 25(OH)D levels were measured in 219 participants in the Tucson Infant Immune Study, a population-based birth cohort. Plasma total IgE and specific IgE levels to 6 aeroallergens were measured at 1, 2, 3, and 5 years. Skin prick test (SPT) positivity (wheal diameter >= 3 mm) and physician-diagnosed active allergic rhinitis and asthma were assessed at age 5 years. Longitudinal models were used to assess the relationship between 25(OH)D and IgE levels. Logistic regression models were used to assess the relationship of 25(OH)D level with SPT positivity, allergic rhinitis, and asthma. Results: The median cord blood 25(OH)D level was 64 nmol/L (interquartile range, 49-81 nmol/L). Relative to the reference group (50-74.9 nmol/L), both low (<50 nmol/L) and high (>= 100 nmol/L) levels were associated with increased total IgE (coefficient = 0.27, P = .006 and coefficient = 0.27, P = .04, respectively) and detectable inhalant allergen-specific IgE (odds ratio = 2.4, P = .03 and odds ratio = 4.0, P = .01, respectively) through age 5 years. High 25(OH)D levels were also associated with increased SPT positivity (odds ratio = 4.0, P = .02). By contrast, the 25(OH)D level was not significantly associated with allergic rhinitis or asthma. Conclusion: Both low and high levels of cord blood 25(OH)D were associated with increased aeroallergen sensitization. The association between vitamin D status and actual allergic diseases merits further study. (J Allergy Clin Immunol 2011;128:1093-9.) C1 [Wright, Anne L.] Univ Arizona, Arizona Hlth Sci Ctr, Arizona Resp Ctr, Tucson, AZ 85724 USA. [Rothers, Janet] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85724 USA. [Wright, Anne L.] Univ Arizona, Dept Pediat, Tucson, AZ 85724 USA. [Halonen, Marilyn] Univ Arizona, Dept Pharmacol, Tucson, AZ 85724 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. RP Wright, AL (reprint author), Univ Arizona, Arizona Hlth Sci Ctr, Arizona Resp Ctr, 1501 N Campbell Ave, Tucson, AZ 85724 USA. EM awright@arc.arizona.edu FU National Institutes of Health [AI 42268, AI 61811] FX This study was funded by National Institutes of Health grants AI 42268 and AI 61811 and the Massachusetts General Hospital Center for D-receptor Activation Research.; Disclosure of potential conflict of interest: J. Rothers, A.L. Wright, and M. Halonen receive research support from the National Institutes of Health. The rest of the authors have declared that they have no conflict of interest. NR 33 TC 77 Z9 77 U1 0 U2 5 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 NOV PY 2011 VL 128 IS 5 BP 1093 EP U275 DI 10.1016/j.jaci.2011.07.015 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA 842FJ UT WOS:000296578200024 PM 21855975 ER PT J AU Truong-Bolduc, QC Dunman, PM Eidem, T Hooper, DC AF Truong-Bolduc, Q. C. Dunman, P. M. Eidem, T. Hooper, D. C. TI Transcriptional Profiling Analysis of the Global Regulator NorG, a GntR-Like Protein of Staphylococcus aureus SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; GENE-EXPRESSION; EFFLUX PUMPS; SARA; MGRA; AGR; VIRULENCE; RESISTANCE; AUTOLYSIS; SYSTEM AB The GntR-like protein NorG has been shown to affect Staphylococcus aureus genes involved in resistance to quinolones and beta-lactams, such as those encoding the NorB and AbcA transporters. To identify the target genes regulated by NorG, we carried out transcriptional-profiling assays using S. aureus RN6390 and its isogenic norG::cat mutant. Our data showed that NorG positively affected the transcription of global regulators mgrA, arlS, and sarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold) genes. The S. aureus predicted MmpL protein showed 53% homology with the MmpL lipid transporter of Mycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA of Staphylococcus hominis. Two pump genes most negatively affected by NorG were the NorC (4-fold) and AbcA (6-fold) genes. Other categories of genes, such as those participating in amino acid, inorganic ion, or nucleotide transporters and metabolism, were also affected by NorG. Real-time reverse transcription (RT)-PCR assays for mgrA, arlS, sarZ, norB, norC, abcA, mmpL, and bcrA-like were carried out to verify microarray data and showed the same level of up-or downregulation by NorG. The norG mutant showed a 2-fold increase in resistance to norfloxacin and rhodamine, both substrates of the NorC transporter, which is consistent with the resistance phenotype conferred by overexpression of norC on a plasmid. These data indicate that NorG has broad regulatory function in S. aureus. C1 [Truong-Bolduc, Q. C.; Hooper, D. C.] Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Dunman, P. M.; Eidem, T.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. [Dunman, P. M.] Univ Rochester, Sch Med & Dent, Dept Microbiol & Immunol, Rochester, NY 14642 USA. [Truong-Bolduc, Q. C.; Hooper, D. C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU U.S. Public Health Service, National Institutes of Health [R37-AI023988]; National Institutes of Health [R01AI073780] FX This work was supported in part by a grant from the U.S. Public Health Service, National Institutes of Health (R37-AI023988 to D.C.H.). Work in the Dunman laboratory was supported in part by National Institutes of Health grant R01AI073780. NR 45 TC 14 Z9 14 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2011 VL 193 IS 22 BP 6207 EP 6214 DI 10.1128/JB.05847-11 PG 8 WC Microbiology SC Microbiology GA 843XF UT WOS:000296709600011 PM 21908673 ER PT J AU Cantor, H AF Cantor, Harvey TI A tribute to Baruj Benacerraf SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Biographical-Item C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Harvey_Cantor@dfci.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2011 VL 121 IS 11 BP 4206 EP 4206 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 840ZY UT WOS:000296482700001 ER PT J AU Ebi, H Corcoran, RB Singh, A Chen, Z Song, Y Lifshits, E Ryan, DP Meyerhardt, JA Benes, C Settleman, J Wong, KK Cantley, LC Engelman, JA AF Ebi, Hiromichi Corcoran, Ryan B. Singh, Anurag Chen, Zhao Song, Youngchul Lifshits, Eugene Ryan, David P. Meyerhardt, Jeffrey A. Benes, Cyril Settleman, Jeffrey Wong, Kwok-Kin Cantley, Lewis C. Engelman, Jeffrey A. TI Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; ANAPLASTIC LYMPHOMA KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; ONCOGENIC ACTIVATION; ACQUIRED-RESISTANCE; MUTATION STATUS; BREAST-CANCER; CYCLIN D1; RAS AB Therapies inhibiting receptor tyrosine kinases (RTKs) are effective against some human cancers when they lead to simultaneous downregulation of PI3K/AKT and MEK/ERK signaling. However, mutant KRAS has the capacity to directly activate ERK and PI3K signaling, and this is thought to underlie the resistance of KRAS mutant cancers to RTK inhibitors. Here, we have elucidated the molecular regulation of both the PI3K/AKT and MEK/ERK signaling pathways in KRAS mutant colorectal cancer cells and identified combination therapies that lead to robust cancer cell apoptosis. KRAS knockdown using shRNA suppressed ERK signaling in all of the human KRAS mutant colorectal cancer cell lines examined. However, no decrease, and actually a modest increase, in AKT phosphorylation was often seen. By performing PI3K immunoprecipitations, we determined that RTKs, often IGF-IR, regulated PI3K signaling in the KRAS mutant cell lines. This conclusion was also supported by the observation that specific RTK inhibition led to marked suppression of PI3K signaling and biochemical assessment of patient specimens. Interestingly, combination of RTK and MEK inhibitors led to concomitant inhibition of PI3K and MEK signaling, marked growth suppression, and robust apoptosis of human KRAS mutant colorectal cancer cell lines in vitro and upon xenografting in mice. These findings provide a framework for utilizing RTK inhibitors in the treatment of KRAS mutant colorectal cancers. C1 [Ebi, Hiromichi; Corcoran, Ryan B.; Singh, Anurag; Song, Youngchul; Lifshits, Eugene; Ryan, David P.; Benes, Cyril; Settleman, Jeffrey; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. [Ebi, Hiromichi; Corcoran, Ryan B.; Singh, Anurag; Chen, Zhao; Ryan, David P.; Meyerhardt, Jeffrey A.; Benes, Cyril; Settleman, Jeffrey; Wong, Kwok-Kin; Cantley, Lewis C.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Chen, Zhao; Meyerhardt, Jeffrey A.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Boston, MA 02129 USA. EM jengelman@partners.org RI Singh, Anurag/C-7347-2014; Cantley, Lewis/D-1800-2014; OI Singh, Anurag/0000-0003-4705-8683; Cantley, Lewis/0000-0002-1298-7653; Ebi, Hiromichi/0000-0003-3155-7576; wong, kwok kin/0000-0001-6323-235X FU NIH Gastrointestinal Cancer SPORE [P50 CA127003, CA120060-01, R01CA140594, 1U01CA141457-01, R01CA122794, R01CA137181, 1RC2CA147940, R01GM41890]; National Cancer Institute Lung SPORE [P50CA090578]; American Association for Cancer Research; V Foundation; American Cancer Society [RSG-06-102-01-CCE]; Ellison Foundation; American Lung Cancer Association; Uniting Against Lung Cancer Foundation; Susan Spooner Research Fund; Kanae Foundation for the Promotion of Medical Science FX This study is supported by grants from the NIH Gastrointestinal Cancer SPORE P50 CA127003 (to J.A. Engelman, J.A. Meyerhardt, and L.C. Cantley), K08 grant CA120060-01 (to J.A. Engelman), R01CA137008-01 (to J.A. Engelman), R01CA140594 (to J.A. Engelman and K.-K. Wong), 1U01CA141457-01 (to J.A. Engelman), R01CA122794 (to K.-K. Wong), R01CA137181 (to K.-K. Wong), 1RC2CA147940 (to K.-K. Wong), R01GM41890 (to L.C. Cantley), National Cancer Institute Lung SPORE P50CA090578 (to J.A. Engelman and K.-K. Wong), the American Association for Cancer Research (to J.A. Engelman), the V Foundation (to J.A. Engelman), American Cancer Society RSG-06-102-01-CCE (to J.A. Engelman), the Ellison Foundation Scholar Award (to J.A. Engelman), the American Lung Cancer Association Lung Cancer Discover Award (to J.A. Engelman), Uniting Against Lung Cancer Foundation (to K.-K. Wong), and the Susan Spooner Research Fund (to K.-K. Wong). H. Ebi was supported by a fellowship from the Kanae Foundation for the Promotion of Medical Science. We also thank Mike Waring and Andrew Cosgrove (Massachusetts General Hospital) for FACS analysis and Anna Kreshock for assistance with IHC. We thank the GI tumor bank at Brigham and Women's Hospital for assistance in obtaining samples for analyses. NR 55 TC 81 Z9 82 U1 1 U2 10 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2011 VL 121 IS 11 BP 4311 EP 4321 DI 10.1172/JCI57909 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 840ZY UT WOS:000296482700015 PM 21985784 ER PT J AU Ma, CHE Omura, T Cobos, EJ Latremoliere, A Ghasemlou, N Brenner, GJ van Veen, E Barrett, L Sawada, T Gao, FY Coppola, G Gertler, F Costigan, M Geschwind, D Woolf, CJ AF Ma, Chi Him Eddie Omura, Takao Cobos, Enrique J. Latremoliere, Alban Ghasemlou, Nader Brenner, Gary J. van Veen, Ed Barrett, Lee Sawada, Tomokazu Gao, Fuying Coppola, Giovanni Gertler, Frank Costigan, Michael Geschwind, Dan Woolf, Clifford J. TI Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TERMINAL SCHWANN-CELLS; CONTRALATERAL C7 TRANSFER; BRACHIAL-PLEXUS INJURIES; POOR FUNCTIONAL RECOVERY; PRIMARY SENSORY NEURONS; DORSAL-ROOT GANGLION; SMOOTH-MUSCLE-CELLS; SPINAL-CORD-INJURY; MYOSIN-II ACTIVITY; SHOCK-PROTEIN 27 AB Although peripheral nerves can regenerate after injury, proximal nerve injury in humans results in minimal restoration of motor function. One possible explanation for this is that injury-induced axonal growth is too slow. Heat shock protein 27 (Hsp27) is a regeneration-associated protein that accelerates axonal growth in vitro. Here, we have shown that it can also do this in mice after peripheral nerve injury. While rapid motor and sensory recovery occurred in mice after a sciatic nerve crush injury, there was little return of motor function after sciatic nerve transection, because of the delay in motor axons reaching their target. This was not due to a failure of axonal growth, because injured motor axons eventually fully re-extended into muscles and sensory function returned; rather, it resulted from a lack of motor end plate reinnervation. Tg mice expressing high levels of Hsp27 demonstrated enhanced restoration of motor function after nerve transection/resuture by enabling motor synapse reinnervation, but only within 5 weeks of injury. In humans with peripheral nerve injuries, shorter wait times to decompression surgery led to improved functional recovery, and, while a return of sensation occurred in all patients, motor recovery was limited. Thus, absence of motor recovery after nerve damage may result from a failure of synapse reformation after prolonged denervation rather than a failure of axonal growth. C1 [Ma, Chi Him Eddie; Omura, Takao; Cobos, Enrique J.; Latremoliere, Alban; Ghasemlou, Nader; Barrett, Lee; Costigan, Michael; Woolf, Clifford J.] Harvard Univ, Childrens Hosp Boston, Sch Med, Program Neurobiol, Boston, MA 02115 USA. [Ma, Chi Him Eddie; Omura, Takao; Cobos, Enrique J.; Latremoliere, Alban; Ghasemlou, Nader; Barrett, Lee; Costigan, Michael; Woolf, Clifford J.] Harvard Univ, Childrens Hosp Boston, Sch Med, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA. [Ma, Chi Him Eddie; Omura, Takao; Cobos, Enrique J.; Latremoliere, Alban; Ghasemlou, Nader; Barrett, Lee; Costigan, Michael; Woolf, Clifford J.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Brenner, Gary J.; Gertler, Frank] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [van Veen, Ed] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Sawada, Tomokazu] Hamamatsu Univ Sch Med, Dept Orthopaed Surg, Shizuoka, Japan. [Gao, Fuying; Coppola, Giovanni; Geschwind, Dan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Program Neurogenet, Los Angeles, CA 90095 USA. [Geschwind, Dan] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA. RP Woolf, CJ (reprint author), Harvard Univ, Childrens Hosp Boston, Sch Med, Program Neurobiol, 300 Longwood Ave,CLS 12258, Boston, MA 02115 USA. EM eddiema@cityu.edu.hk; clifford.woolf@childrens.harvard.edu RI Cobos, Enrique/E-9077-2016; OI MA, Chi Him Eddie/0000-0003-2054-0445; Ghasemlou, Nader/0000-0002-1696-7342 FU NIH [NS038253, FBG 068678]; Miriam and Sheldon G. Adelson Medical Research Foundation; Hong Kong Croucher Foundation; IRP-IFP Switzerland; MICINN/Fulbright program; Fonds de la recherche en sante du Quebec; Massachusetts General Hospital Neuroscience Center Vector Development and Production Core (NIH) [P30NS045776] FX We thank the NIH (to C.J. Woolf; NS038253, FBG 068678), Miriam and Sheldon G. Adelson Medical Research Foundation (to C.J. Woolf, D. Geschwind, and G. Coppola), Hong Kong Croucher Foundation Fellowship (CHEM), IRP-IFP Switzerland (to M. Costigan and G. Coppola), the MICINN/Fulbright program (to E.J. Cobos), and the Fonds de la recherche en sante du Quebec (to N. Ghasemlou) for financial support. We also thank the Massachusetts General Hospital Neuroscience Center Vector Development and Production Core (NIH grant P30NS045776) for production of lentivirus vectors. NR 72 TC 56 Z9 58 U1 1 U2 12 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2011 VL 121 IS 11 BP 4332 EP 4347 DI 10.1172/JCI58675 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 840ZY UT WOS:000296482700017 PM 21965333 ER PT J AU Faul, C Amaral, AP Oskouei, B Hu, MC Sloan, A Isakova, T Gutierrez, OM Aguillon-Prada, R Lincoln, J Hare, JM Mundel, P Morales, A Scialla, J Fischer, M Soliman, EZ Chen, J Go, AS Rosas, SE Nessel, L Townsend, RR Feldman, HI Sutton, MS Ojo, A Gadegbeku, C Di Marco, GS Reuter, S Kentrup, D Tiemann, K Brand, M Hill, JA Moe, OW Kuro-o, M Kusek, JW Keane, MG Wolf, M AF Faul, Christian Amaral, Ansel P. Oskouei, Behzad Hu, Ming-Chang Sloan, Alexis Isakova, Tamara Gutierrez, Orlando M. Aguillon-Prada, Robier Lincoln, Joy Hare, Joshua M. Mundel, Peter Morales, Azorides Scialla, Julia Fischer, Michael Soliman, Elsayed Z. Chen, Jing Go, Alan S. Rosas, Sylvia E. Nessel, Lisa Townsend, Raymond R. Feldman, Harold I. Sutton, Martin St. John Ojo, Akinlolu Gadegbeku, Crystal Di Marco, Giovana Seno Reuter, Stefan Kentrup, Dominik Tiemann, Klaus Brand, Marcus Hill, Joseph A. Moe, Orson W. Kuro-o, Makoto Kusek, John W. Keane, Martin G. Wolf, Myles TI FGF23 induces left ventricular hypertrophy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CHRONIC KIDNEY-DISEASE; GROWTH-FACTOR 23; MYOSIN HEAVY-CHAIN; STAGE RENAL-DISEASE; X-LINKED HYPOPHOSPHATEMIA; RECEPTOR TYROSINE KINASES; RAT CARDIAC MYOCYTES; GENE-EXPRESSION; MYOCARDIAL PERFORMANCE; SIGNALING PATHWAYS AB Chronic kidney disease (CKD) is a public health epidemic that increases risk of death due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiovascular disease in individuals with CKD. Elevated levels of FGF23 have been linked to greater risks of LVH and mortality in patients with CKD, but whether these risks represent causal effects of FGF23 is unknown. Here, we report that elevated FGF23 levels are independently associated with LVH in a large, racially diverse CKD cohort. FGF23 caused pathological hypertrophy of isolated rat cardiomyocytes via FGF receptor-dependent activation of the calcineurin-NFAT signaling pathway, but this effect was independent of klotho, the coreceptor for FGF23 in the kidney and parathyroid glands. Intrarnyocardial or intravenous injection of FGF23 in wild-type mice resulted in LVH, and klotho-deficient mice demonstrated elevated FGF23 levels and LVH. In an established animal model of CKD, treatment with an FGF-receptor blocker attenuated LVH, although no change in blood pressure was observed. These results unveil a klotho-independent, causal role for FGF23 in the pathogenesis of LVH and suggest that chronically elevated FGF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD. C1 [Faul, Christian; Amaral, Ansel P.; Sloan, Alexis; Isakova, Tamara; Aguillon-Prada, Robier; Scialla, Julia; Wolf, Myles] Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, Miami, FL 33136 USA. [Faul, Christian; Amaral, Ansel P.; Sloan, Alexis] Univ Miami, Miller Sch Med, Dept Cell Biol & Anat, Miami, FL 33136 USA. [Oskouei, Behzad; Hare, Joshua M.] Univ Miami, Miller Sch Med, Interdisciplinary Stem Cell Inst, Miami, FL 33136 USA. [Hu, Ming-Chang; Hill, Joseph A.; Moe, Orson W.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Hu, Ming-Chang] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Hu, Ming-Chang; Kuro-o, Makoto] Univ Texas SW Med Ctr Dallas, Charles & Jane Pak Ctr Mineral Metab & Clin Res, Dallas, TX 75390 USA. [Gutierrez, Orlando M.] Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Gutierrez, Orlando M.] Univ Alabama, Sch Med, Dept Med, Div Nephrol, Birmingham, AL USA. [Lincoln, Joy] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA. [Lincoln, Joy] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA. [Mundel, Peter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Boston, MA USA. [Morales, Azorides] Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA. [Fischer, Michael] Jesse Brown VA Med Ctr, Dept Med, Chicago, IL USA. [Fischer, Michael] Univ Illinois, Med Ctr, Chicago, IL USA. [Fischer, Michael] Edward Hines Jr VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA. [Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Epidemiol Cardiol Res Ctr, Winston Salem, NC USA. [Chen, Jing] Tulane Sch Med, Dept Med, New Orleans, LA USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, San Francisco, CA USA. [Go, Alan S.] UCSF, Dept Epidemiol, San Francisco, CA USA. [Go, Alan S.] UCSF, Dept Biostat, San Francisco, CA USA. [Go, Alan S.] UCSF, Dept Med, San Francisco, CA USA. [Rosas, Sylvia E.; Townsend, Raymond R.; Feldman, Harold I.] Univ Penn, Sch Med, Dept Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. [Nessel, Lisa; Feldman, Harold I.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Sutton, Martin St. John; Keane, Martin G.] Univ Penn, Sch Med, Dept Med, Div Cardiol, Philadelphia, PA 19104 USA. [Gadegbeku, Crystal] Temple Univ, Schostl Med, Dept Internal Med, Sect Nephrol & Kidney Transplantat, Philadelphia, PA 19122 USA. [Ojo, Akinlolu] Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA. [Di Marco, Giovana Seno; Reuter, Stefan; Kentrup, Dominik; Brand, Marcus] Univ Munster, Dept Internal Med D, D-4400 Munster, Germany. [Tiemann, Klaus] Univ Munster, Dept Cardiol & Angiol, Munster, Germany. [Hill, Joseph A.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. [Moe, Orson W.] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA. [Kuro-o, Makoto] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Kusek, John W.] NIDDK, Bethesda, MD USA. RP Wolf, M (reprint author), 1120 NW 14th St,Suite 819, Miami, FL 33136 USA. EM cfaul@med.miami.edu; mwolf2@med.miami.edu RI Rosas, Sylvia/D-1106-2009; OI Seno Di Marco, Giovana/0000-0002-1877-638X FU NephCure Foundation; American Heart Association; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center; George M. O'Brien Kidney Research Core Center/UT Southwestern Medical Center at Dallas [NIH P30DK-07938]; Stifterverband fur die Deutsche Wissenschaft and Simon-Claussen-Stiftung [H 1405409999915626]; Inter-disciplinary Research Initiative of the University of Miami Miller School of Medicine; Department of Veterans Affairs; National Institutes of Health [F30DK091057, K23DK087858, K23DK081673, R01DK091392, R01AG019712, R01DK076116, R01DK081374]; National Institute of Diabetes and Digestive and Kidney Diseases [5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, 5U01DK060902]; institutional Clinical Translational Science Awards; NIH; University of Pennsylvania [UL1 RR024134]; Johns Hopkins University [UL1 RR025005]; University of Maryland [GCRC M01 RR16500]; Case Western Reserve University Clinical and Translational Science Collaborative (University Hospitals of Cleveland, Cleveland Clinic Foundation, and MetroHealth) [UL1 RR024989]; University of Michigan [GCRC M01 RR-000042, UL1 RR024986]; University of Illinois at Chicago [UL1 RR029879]; Tulane/LSU/Charity Hospital General Clinical Research Center [RR05096]; Kaiser-UCSF-CTSI [RR024131]; Abbott Laboratories; Ardelyx; Genzyme FX This study was supported by grants from the NephCure Foundation (to C. Faul), the American Heart Association (to C. Faul and M.C. Hu), the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center (to M.C. Hu), the George M. O'Brien Kidney Research Core Center/UT Southwestern Medical Center at Dallas (NIH P30DK-07938 to O.W. Moe), the Stifterverband fur die Deutsche Wissenschaft and Simon-Claussen-Stiftung (H 1405409999915626 to M. Brand), the Inter-disciplinary Research Initiative of the University of Miami Miller School of Medicine (to C. Faul, J.M. Hare, and M. Wolf), a Health Services Research and Development Service Career Development Award from the Department of Veterans Affairs (to M.J. Fischer), and grants F30DK091057 (to A.P. Amaral), K23DK087858 (to T. Isakova), K23DK081673 (to O.M. Gutierrez), R01DK091392 (to M.C. Hu, M. Kuro-o, and O.W. Moe), R01AG019712 (to M. Kuro-o), R01DK076116 (to M. Wolf), and R01DK081374 (to M. Wolf) from the National Institutes of Health. Funding for the CRIC study was obtained under a cooperative agreement from National Institute of Diabetes and Digestive and Kidney Diseases (grant no. 5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, and 5U01DK060902). In addition, this work was supported in part by the following institutional Clinical Translational Science Awards and other NIH grants: University of Pennsylvania, UL1 RR024134; Johns Hopkins University, UL1 RR025005; University of Maryland, GCRC M01 RR16500; Case Western Reserve University Clinical and Translational Science Collaborative (University Hospitals of Cleveland, Cleveland Clinic Foundation, and MetroHealth), UL1 RR024989; University of Michigan, GCRC M01 RR-000042 and UL1 RR024986; University of Illinois at Chicago, UL1 RR029879; Tulane/LSU/Charity Hospital General Clinical Research Center, RR05096; and Kaiser-UCSF-CTSI, RR024131.; Tamara Isakova has served as a consultant and received honoraria from Shire. Orlando M. Gutierrez has received honoraria from Genzyme. Sylvia E. Rosas has received research support from Abbott Laboratories. Makoto Kuro-o has received research support from Ardelyx and Genzyme and honoraria from Amgen and Genzyme. Myles Wolf has served as a consultant or received honoraria from Abbott Laboratories, Amgen, Ardelyx, Baxter, Cytochroma, Genzyme, Luitpold Pharmaceuticals Inc., Novartis, Mitsubishi, and Shire. NR 89 TC 615 Z9 645 U1 5 U2 31 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2011 VL 121 IS 11 BP 4393 EP 4408 DI 10.1172/JCI46122 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 840ZY UT WOS:000296482700022 PM 21985788 ER PT J AU Loehrer, PJ Feng, Y Cardenes, H Wagner, L Brell, JM Cella, D Flynn, P Ramanathan, RK Crane, CH Alberts, SR Benson, A AF Loehrer, Patrick J., Sr. Feng, Yang Cardenes, Higinia Wagner, Lynne Brell, Joanna M. Cella, David Flynn, Patrick Ramanathan, Ramesh K. Crane, Christopher H. Alberts, Steven R. Benson, Al B., III TI Gemcitabine Alone Versus Gemcitabine Plus Radiotherapy in Patients With Locally Advanced Pancreatic Cancer: An Eastern Cooperative Oncology Group Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-I TRIAL; RADIATION-DOSE ESCALATION; CONCURRENT RADIOTHERAPY; III TRIAL; CISPLATIN; THERAPY; CHEMORADIOTHERAPY; ADENOCARCINOMA; INFUSION; RADIOCHEMOTHERAPY AB Purpose The purpose of this trial was to evaluate the role of radiation therapy with concurrent gemcitabine (GEM) compared with GEM alone in patients with localized unresectable pancreatic cancer. Patients and Methods Patients with localized unresectable adenocarcinoma of the pancreas were randomly assigned to receive GEM alone (at 1,000 mg/m(2)/wk for weeks 1 to 6, followed by 1 week rest, then for 3 of 4 weeks) or GEM (600 mg/m2/wk for weeks 1 to 5, then 4 weeks later 1,000 mg/m(2) for 3 of 4 weeks) plus radiotherapy (starting on day 1, 1.8 Gy/Fx for total of 50.4 Gy). Measurement of quality of life using the Functional Assessment of Cancer Therapy-Hepatobiliary questionnaire was also performed. Results Of 74 patients entered on trial and randomly assigned to receive GEM alone (arm A; n = 37) or GEM plus radiation (arm B; n = 34), patients in arm B had greater incidence of grades 4 and 5 toxicities (41% v 9%), but grades 3 and 4 toxicities combined were similar (77% in A v 79% in B). No statistical differences were seen in quality of life measurements at 6, 15 to 16, and 36 weeks. The primary end point was survival, which was 9.2 months (95% CI, 7.9 to 11.4 months) and 11.1 months (95% CI, 7.6 to 15.5 months) for arms A and B, respectively (one-sided P = .017 by stratified log-rank test). Conclusion This trial demonstrates improved overall survival with the addition of radiation therapy to GEM in patients with localized unresectable pancreatic cancer, with acceptable toxicity. J Clin Oncol 29: 4105-4112. (C) 2011 by American Society of Clinical Oncology C1 [Loehrer, Patrick J., Sr.; Cardenes, Higinia] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA. [Feng, Yang] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wagner, Lynne; Cella, David; Benson, Al B., III] Northwestern Univ, Sch Med, Chicago, IL USA. [Brell, Joanna M.] Case Western Reserve Univ, Ireland Canc Ctr, Cleveland, OH 44106 USA. [Flynn, Patrick] Minneapolis Hematol Oncol, Minneapolis, MN USA. [Alberts, Steven R.] Mayo Clin, Rochester, MN USA. [Ramanathan, Ramesh K.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Crane, Christopher H.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Loehrer, PJ (reprint author), Indiana Univ, Melvin & Bren Simon Canc Ctr, 980 W Walnut St,Suite C528, Indianapolis, IN 46202 USA. EM ploehrer@iupui.edu FU Eli Lilly FX Research Funding: Patrick J. Loehrer Sr, Eli Lilly NR 38 TC 230 Z9 232 U1 1 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2011 VL 29 IS 31 BP 4105 EP 4112 DI 10.1200/JCO.2011.34.8904 PG 8 WC Oncology SC Oncology GA 842NB UT WOS:000296605100013 PM 21969502 ER PT J AU Saboo, SS Jagannathan, JP Krajewski, KM O'Regan, K Hornick, JL Fisher, DC Ramaiya, N AF Saboo, Sachin S. Jagannathan, Jyothi P. Krajewski, Katherine M. O'Regan, Kevin Hornick, Jason L. Fisher, David C. Ramaiya, Nikhil TI Symptomatic Extranodal Rosai-Dorfman Disease Treated With Steroids, Radiation, and Surgery SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID ASSOCIATION C1 [Saboo, Sachin S.; Jagannathan, Jyothi P.; Krajewski, Katherine M.; O'Regan, Kevin; Fisher, David C.; Ramaiya, Nikhil] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hornick, Jason L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Saboo, SS (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 10 TC 6 Z9 7 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2011 VL 29 IS 31 BP E772 EP E775 DI 10.1200/JCO.2011.36.9967 PG 4 WC Oncology SC Oncology GA 842NB UT WOS:000296605100002 PM 21931038 ER PT J AU Schirmer, P Winters, M Holodniy, M AF Schirmer, P. Winters, M. Holodniy, M. TI HIV-HBV vaccine escape mutant infection with loss of HBV surface antibody and persistent HBV viremia on tenofovir/emtricitabine without antiviral resistance SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE HIV; HBV; Vaccine escape; Tenofovir; Emtricitabine ID HEPATITIS-B; COINFECTION; ANTIGEN; CARRIER AB We report a case of acute hepatitis B virus genotype A vaccine escape mutant infection with loss of HBV vaccine-induced seropositivity in a HIV-1 infected patient. His HBV is unresponsive to tenofovir/emtricitabine treatment demonstrated by persistent viremia despite lacking known resistance mutations and while having an undetectable HIV-1 viral load. Published by Elsevier B. V. C1 [Schirmer, P.; Holodniy, M.] US Dept Vet Affairs, Off Publ Hlth, Palo Alto, CA 94304 USA. [Winters, M.; Holodniy, M.] Stanford Univ, Palo Alto, CA 94304 USA. RP Schirmer, P (reprint author), US Dept Vet Affairs, Off Publ Hlth Surveillance & Res, 3801 Miranda Ave,132, Palo Alto, CA 94304 USA. EM patricia.schirmer@va.gov FU Department of Veterans Affairs [HOM0055] FX This work was supported by a Department of Veterans Affairs grant [HOM0055] to Mark Holodniy. NR 14 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD NOV PY 2011 VL 52 IS 3 BP 261 EP 264 DI 10.1016/j.jcv.2011.07.014 PG 4 WC Virology SC Virology GA 842AF UT WOS:000296556800021 PM 21840252 ER EF