FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Johansen, KL AF Johansen, Kirsten L. TI Is Predialysis Nephrology Care Worthwhile? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 4150 Clement St,111J, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu NR 8 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD AUG 8 PY 2011 VL 171 IS 15 BP 1317 EP 1318 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 804GR UT WOS:000293642800002 PM 21824944 ER PT J AU Kistler, CE Kirby, KA Lee, D Casadei, MA Walter, LC AF Kistler, Christine E. Kirby, Katharine A. Lee, Delia Casadei, Michele A. Walter, Louise C. TI Long-term Outcomes Following Positive Fecal Occult Blood Test Results in Older Adults Benefits and Burdens SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID COMPLETE DIAGNOSTIC EVALUATION; AMERICAN-CANCER-SOCIETY; COLORECTAL-CANCER; ELDERLY-PATIENTS; COLONOSCOPY SURVEILLANCE; COMORBIDITY INDEX; LIFE EXPECTANCY; UNITED-STATES; GUIDELINES; AGE AB Background: In the United States, older adults have low rates of follow-up colonoscopy after a positive fecal occult blood test (FOBT) result. The long-term outcomes of these real world practices and their associated benefits and burdens are unknown. Methods: Longitudinal cohort study of 212 patients 70 years or older with a positive FOBT result at 4 Veteran Affairs (VA) facilities in 2001 and followed up through 2008. We determined the frequency of downstream outcomes during the 7 years of follow-up, including procedures, colonoscopic findings, outcomes of treatment, complications, and mortality based on chart review and national VA and Medicare data. Net burden or benefit from screening and follow-up was determined according to each patient's life expectancy. Life expectancy was classified into 3 categories: best (age, 70-79 years and Charlson-Deyo comorbidity index [CCI], 0), average, and worst (age, 70-84 years and CCI, >= 4 or age, >= 85 years and CCI, >= 1). Results: Fifty-six percent of patients received follow-up colonoscopy (118 of 212), which found 34 sig-nificant adenomas and 6 cancers. Ten percent experienced complications from colonoscopy or cancer treatment (12 of 118). Forty-six percent of those without follow-up colonoscopy died of other causes within 5 years of FOBT (43 of 94), while 3 died of colorectal cancer within 5 years. Eighty-seven percent of patients with worst life expectancy experienced a net burden from screening (26 of 30) as did 70% with average life expectancy (92 of 131) and 65% with best life expectancy (35 of 51) (P=.048 for trend). Conclusions: Over a 7-year period, older adults with best life expectancy were less likely to experience a net burden from current screening and follow-up practices than are those with worst life expectancy. The net burden could be decreased by better targeting FOBT screening and follow-up to healthy older adults. C1 [Kistler, Christine E.] Univ N Carolina, Dept Family Med, Chapel Hill, NC 27599 USA. [Kirby, Katharine A.; Casadei, Michele A.; Walter, Louise C.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Kirby, Katharine A.; Casadei, Michele A.; Walter, Louise C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lee, Delia] Univ Arkansas, Sch Med, Fayetteville, AR 72701 USA. RP Kistler, CE (reprint author), Univ N Carolina, Dept Family Med, 590 Manning Dr,CB 7595, Chapel Hill, NC 27599 USA. EM Christine_Kistler@med.unc.edu FU National Institute on Aging [T32 AG000212-16]; Agency for Healthcare Research and Quality Mentored Career Development Program in Comparative Effectiveness Development [K12 HS19468-01]; Cecil G. Sheps Center for Health Services Research; Lineberger Cancer Center at the University of North Carolina at Chapel Hill; VA Health Services Research and Development [IIR-04-427]; National Cancer Institute [1R01CA134425]; VA Quality Scholars Program FX Work for this research was supported by the VA Quality Scholars Program, National Institute on Aging grant T32 AG000212-16, Agency for Healthcare Research and Quality Mentored Career Development Program in Comparative Effectiveness Development grant K12 HS19468-01, the Cecil G. Sheps Center for Health Services Research, and the Lineberger Cancer Center at the University of North Carolina at Chapel Hill (Dr Kistler); and by VA Health Services Research and Development grant IIR-04-427 and National Cancer Institute grant 1R01CA134425 (Dr Walter). NR 41 TC 17 Z9 17 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD AUG 8 PY 2011 VL 171 IS 15 BP 1344 EP 1351 DI 10.1001/archinternmed.2011.206 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 804GR UT WOS:000293642800007 PM 21555655 ER PT J AU Newton, KM Grady, D AF Newton, Katherine M. Grady, Deborah TI Soy Isoflavones for Prevention of Menopausal Bone Loss and Vasomotor Symptoms SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; MILD COGNITIVE IMPAIRMENT; HEALTH INITIATIVE MEMORY; ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; METAANALYSIS; DEMENTIA C1 [Grady, Deborah] Univ Calif San Francisco, Dept Med, San Francisco, CA 94115 USA. [Grady, Deborah] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. [Newton, Katherine M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. RP Grady, D (reprint author), Univ Calif San Francisco, Dept Med, 1635 Divisadero St,Ste 600, San Francisco, CA 94115 USA. NR 12 TC 7 Z9 7 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD AUG 8 PY 2011 VL 171 IS 15 BP 1369 EP 1370 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 804GR UT WOS:000293642800012 PM 21824951 ER PT J AU Huang, SL Shen, Q Duong, TQ AF Huang, Shiliang Shen, Qiang Duong, Timothy Q. TI Quantitative prediction of acute ischemic tissue fate using support vector machine SO BRAIN RESEARCH LA English DT Article DE SVM; fMRI; ANN; Perfusion-diffusion mismatch; Predictive model; DWI; PWI; ADC; CBF; Spatial infarction incidence ID NEURAL-NETWORK; CEREBRAL-ISCHEMIA; FOCAL ISCHEMIA; FUNCTIONAL MRI; BRAIN-INJURY; PERFUSION; STROKE; PENUMBRA; CLASSIFICATION; CONSUMPTION AB Accurate and quantitative prediction of ischemic tissue fate could improve decision-making in the clinical treatment of acute stroke. The goal of the present study is to explore the novel use of support vector machine (SVM) to predict infarct on a pixel-by-pixel basis using only acute cerebral blood flow (CBF), apparent diffusion coefficient (ADC) MRI data. The efficacy of SVM prediction model was tested on three stroke groups: 30-min, 60-min, and permanent middle cerebral-artery occlusion (n=12 rats for each group). CBF, ADC and relaxation time constant (T2) were acquired during the acute phase up to 3 h and again at 24 h. Infarct was predicted using only acute (30-min) stroke data. Receiver-operating characteristic (ROC) analysis was used to quantify prediction accuracy. The areas under the receiver-operating curves were 86+/-2.7%, 89+/-1.4%, and 93+/-0.8% using ADC+CBF data for the 30-min, 60-min and permanent middle cerebral artery occlusion (MCAO) group, respectively. Adding neighboring pixel information and spatial infarction incidence improved performance to 88 +/-2.8%, 94+/-0.8%, and 97+/-0.9%, respectively. SVM prediction compares favorably to a previously published artificial neural network (ANN) prediction algorithm operated on the same data sets. SVM prediction model has the potential to provide quantitative frameworks to aid clinical decision-making in the treatment of acute stroke. (C) 2011 Elsevier B.V. All rights reserved. C1 [Huang, Shiliang; Shen, Qiang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008; Shen, Qiang/B-8784-2008; Huang, Shiliang/F-3143-2010 OI Shen, Qiang/0000-0002-4287-3403; FU NIH [R01-NS45879]; American Heart Association [EIA 0940104N, SDG-0430020N, SDG-0830293N] FX This work was supported by the NIH (R01-NS45879) and the American Heart Association (EIA 0940104N, SDG-0430020N and SDG-0830293N). NR 34 TC 12 Z9 12 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 8 PY 2011 VL 1405 BP 77 EP 84 DI 10.1016/j.brainres.2011.05.066 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 807VW UT WOS:000293932100008 PM 21741624 ER PT J AU Volpp, KG Asch, DA Galvin, R Loewenstein, G AF Volpp, Kevin G. Asch, David A. Galvin, Robert Loewenstein, George TI Redesigning Employee Health Incentives - Lessons from Behavioral Economics SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Volpp, Kevin G.; Asch, David A.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Asch, David A.; Loewenstein, George] Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Asch, David A.; Loewenstein, George] Univ Penn, Penn CMU Roybal Ctr Behav Econ & Hlth, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Asch, David A.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Asch, David A.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Galvin, Robert] Equity Healthcare, Black Stone Grp, New York, NY USA. [Galvin, Robert] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Loewenstein, George] Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. RP Volpp, KG (reprint author), Univ Penn, Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. FU NIA NIH HHS [P30 AG034546] NR 5 TC 91 Z9 91 U1 0 U2 18 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 AUG 4 PY 2011 VL 365 IS 5 BP 388 EP 390 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 801NW UT WOS:000293447800002 PM 21812669 ER PT J AU Moorman, AJ Stratton, JR Levy, WC AF Moorman, Alec J. Stratton, John R. Levy, Wayne C. TI Clonidine therapy in patients with heart failure improves exercise efficiency, functional class and symptoms SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Heart failure; Sympathetic nervous system; Exercise; Clonidine ID SYMPATHETIC INHIBITION; MORTALITY C1 [Moorman, Alec J.; Levy, Wayne C.] Univ Washington, Div Cardiol, Dept Med, Sch Med, Seattle, WA 98177 USA. [Stratton, John R.] VA Puget Sound Hlth Care Syst, Dept Med, Div Cardiol, Seattle, WA USA. RP Moorman, AJ (reprint author), Univ Washington, Div Cardiol, Dept Med, Sch Med, Box 356422,1959 NE Pacific St, Seattle, WA 98177 USA. EM amoorman@u.washington.edu NR 9 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD AUG 4 PY 2011 VL 150 IS 3 BP 372 EP 373 DI 10.1016/j.ijcard.2011.05.091 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 795EW UT WOS:000292956200050 PM 21640409 ER PT J AU Ioannou, GN AF Ioannou, George N. TI Hepatitis B Virus in the United States RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. NR 2 TC 0 Z9 0 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 2 PY 2011 VL 155 IS 3 BP 205 EP + DI 10.7326/0003-4819-155-3-201108020-00022 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 800DJ UT WOS:000293339600018 ER PT J AU Wilson, R Lewis, SA Dicianno, BE AF Wilson, Richard Lewis, Steven A. Dicianno, Brad E. TI Targeted Preventive Care May Be Needed for Adults with Congenital Spine Anomalies SO PM&R LA English DT Article ID PRESSURE ULCERS; HEALTH-CARE; CORD-INJURY; BIFIDA; HOSPITALIZATIONS; GUIDELINES; RISK AB Objective: To compare hospitalizations caused by spina bifida sensitive conditions, ambulatory care sensitive conditions in adults with spina bifida and in the general population, our aim was to provide information about whether preventive health efforts already underway in the hospitalized general population are adequate for preventive care in spina bifida and congenital spine anomalies. Design: Retrospective secondary data analysis. Patients (or Participants): Records of hospitalized individuals who were 18 years of age and older. Methods: Comparison between individuals hospitalized with spina bifida and the general population using data from the California State Inpatient Database from the Healthcare Cost and Utilization Project for 2004 of adults. Main Outcome Measurements: Prevalence of spina bifida sensitive conditions and ambulatory care sensitive conditions as reason for hospitalization and 30-day readmission. Results: As compared with the general population, persons with spina bifida who were hospitalized in 2004 had a significantly greater number of hospitalizations, number of hospitalizations associated with both spina bifida sensitive conditions and ambulatory care sensitive conditions, and number of 30-day readmissions. Stratification by age shows that the admissions for spina bifida sensitive conditions were greater in persons with spina bifida than in the general population for all age groups. In contrast, only in the youngest age group did those with spina bifida experience greater hospitalizations for ambulatory care-sensitive conditions. Conclusions: This study provides further evidence that persons with spina bifida have hospitalizations that are beyond what the general population experiences. These conditions may be potentially preventable with appropriate ambulatory care. This group also had a greater risk for readmission within 30 days of discharge from their last hospitalization. More research is needed on the efficacy of programs aimed at prevention of these conditions. PM R 2011;3:730-738 C1 [Wilson, Richard] Case Western Reserve Univ, Metrohlth Med Ctr, MetroHlth Rehabil Inst Ohio, Cleveland, OH USA. [Wilson, Richard] Cleveland Funct Elect Stimulat Ctr, Cleveland, OH USA. [Lewis, Steven A.] Case Western Reserve Univ, Metrohlth Med Ctr, Ctr Hlth Care Res & Policy, Cleveland, OH USA. [Dicianno, Brad E.] Univ Pittsburgh, Human Engn Res Labs, Pittsburgh, PA USA. [Dicianno, Brad E.] US Dept Vet Affairs, Pittsburgh, PA USA. [Dicianno, Brad E.] Univ Pittsburgh, Adult Spina Bifida Clin, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Wilson, R (reprint author), 2500 MetroHlth Dr,S1-107E, Cleveland, OH 44109 USA. EM rwilson@metrohealth.org OI Dicianno, Brad/0000-0003-0738-0192 NR 37 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD AUG PY 2011 VL 3 IS 8 BP 730 EP 738 DI 10.1016/j.pmrj.2011.05.021 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 961BD UT WOS:000305438000008 PM 21871417 ER PT J AU Porter, JN Jedema, HP Baeg, EH Bradberry, CW AF Porter, J. N. Jedema, H. P. Baeg, E. H. Bradberry, C. W. TI IMPACT OF COCAINE SELF-ADMINISTRATION ON COGNITIVE FLEXIBILITY AND ATTENTIONAL PERFORMANCE IN RHESUS MONKEYS SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract CT 14th Biennial Meeting of the European-Behavioural-Pharmacology-Society CY AUG 26-29, 2011 CL Amsterdam, NETHERLANDS SP European Behav Pharmacol Soc C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD AUG PY 2011 VL 22 SU S BP E11 EP E12 PG 2 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 893OM UT WOS:000300365200043 ER PT J AU Antony, B Abramoff, MD Tang, L Ramdas, WD Vingerling, JR Jansonius, NM Lee, K Kwon, YH Sonka, M Garvin, MK AF Antony, Bhavna Abramoff, Michael D. Tang, Li Ramdas, Wishal D. Vingerling, Johannes R. Jansonius, Nomdo M. Lee, Kyungmoo Kwon, Young H. Sonka, Milan Garvin, Mona K. TI Automated 3-D method for the correction of axial artifacts in spectral-domain optical coherence tomography images SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID SEGMENTATION; REGISTRATION; ROTTERDAM AB The 3-D spectral-domain optical coherence tomography (SD-OCT) images of the retina often do not reflect the true shape of the retina and are distorted differently along the x and y axes. In this paper, we propose a novel technique that uses thin-plate splines in two stages to estimate and correct the distinct axial artifacts in SD-OCT images. The method was quantitatively validated using nine pairs of OCT scans obtained with orthogonal fast-scanning axes, where a segmented surface was compared after both datasets had been corrected. The mean unsigned difference computed between the locations of this artifact-corrected surface after the single-spline and dual-spline correction was 23.36 +/- 4.04 mu m and 5.94 +/- 1.09 mu m, respectively, and showed a significant difference (p < 0.001 from two-tailed paired t-test). The method was also validated using depth maps constructed from stereo fundus photographs of the optic nerve head, which were compared to the flattened top surface from the OCT datasets. Significant differences (p < 0.001) were noted between the artifact-corrected datasets and the original datasets, where the mean unsigned differences computed over 30 optic-nerve-head-centered scans (in normalized units) were 0.134 +/- 0.035 and 0.302 +/- 0.134, respectively. (C) 2011 Optical Society of America C1 [Antony, Bhavna; Abramoff, Michael D.; Lee, Kyungmoo; Sonka, Milan; Garvin, Mona K.] Univ Iowa, Dept Elect & Comp Engn, Iowa City, IA 52242 USA. [Abramoff, Michael D.; Tang, Li; Kwon, Young H.; Sonka, Milan] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA. [Abramoff, Michael D.; Garvin, Mona K.] US Dept Vet Affairs, Iowa City, IA USA. [Ramdas, Wishal D.; Vingerling, Johannes R.] Erasmus MC, Depts Ophthalmol & Epidemiol, Rotterdam, Netherlands. [Jansonius, Nomdo M.] Univ Groningen, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands. RP Antony, B (reprint author), Univ Iowa, Dept Elect & Comp Engn, Iowa City, IA 52242 USA. EM mona-garvin@uiowa.edu RI Abramoff, Michael/A-5836-2009 OI Abramoff, Michael/0000-0002-3490-0037 FU Department of Veterans Affairs; National Institutes of Health [NEI EY017066, R01 EY018853, R01 EY019112]; Research to Prevent Blindness, New York, NY; Marlene S. and Leonard A. Hadley Glaucoma Research Fund; Stichting Lijf en Leven, Krimpen aan de Lek; MD Fonds, Utrecht; Rotterdamse Vereniging Blindenbelangen, Rotterdam; Stichting Oogfonds Nederland, Utrecht; Blindenpenning, Amsterdam; Blindenhulp, The Hague; Algemene Nederlandse Vereniging ter Voorkoming van Blindheid (ANVVB), Doorn; Landelijke Stichting voor Blinden en Slechtzienden, Utrecht; Swart van Essen, Rotterdam; Stichting Winckel-Sweep, Utrecht; Henkes Stichting, Rotterdam; Lamris Ootech BV, Nieuwegein; Medical Workshop, de Meern; Topcon Europe BV, Capelle aan de IJssel in the Netherlands; Heidelberg Engineering, Dossenheim, Germany FX This work was supported in part by the Department of Veterans Affairs; the National Institutes of Health grants NEI EY017066, R01 EY018853 and R01 EY019112; Research to Prevent Blindness, New York, NY; Marlene S. and Leonard A. Hadley Glaucoma Research Fund; Stichting Lijf en Leven, Krimpen aan de Lek; MD Fonds, Utrecht; Rotterdamse Vereniging Blindenbelangen, Rotterdam; Stichting Oogfonds Nederland, Utrecht; Blindenpenning, Amsterdam; Blindenhulp, The Hague; Algemene Nederlandse Vereniging ter Voorkoming van Blindheid (ANVVB), Doorn; Landelijke Stichting voor Blinden en Slechtzienden, Utrecht; Swart van Essen, Rotterdam; Stichting Winckel-Sweep, Utrecht; Henkes Stichting, Rotterdam; Lamris Ootech BV, Nieuwegein; Medical Workshop, de Meern; Topcon Europe BV, Capelle aan de IJssel, all in the Netherlands, and Heidelberg Engineering, Dossenheim, Germany. NR 24 TC 17 Z9 17 U1 2 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD AUG 1 PY 2011 VL 2 IS 8 BP 2403 EP 2416 PG 14 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 886VN UT WOS:000299882100029 PM 21833377 ER PT J AU Zhang, Y Wey, HY Nateras, OSE Peng, Q De La Garza, BH Duong, TQ AF Zhang, Yi Wey, Hsiao-Ying Nateras, Oscar San Emeterio Peng, Qi De La Garza, Bryan H. Duong, Timothy Q. TI Anatomical, Blood Oxygenation Level-Dependent, and Blood Flow MRI of Nonhuman Primate (Baboon) Retina SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE high-resolution MRI; blood oxygenation level-dependent; blood flow; choroid; retinal diseases; high-resolution fMRI; hyperoxia; hypercapnia ID OPTICAL COHERENCE TOMOGRAPHY; FUNCTIONAL MRI; LAMINAR SPECIFICITY; ENHANCED MRI; RESOLUTION; FMRI; RAT; DEGENERATION; HYPERCAPNIA; HYPEROXIA AB The goal of this study was to demonstrate high-resolution anatomical, blood oxygenation level-dependent, and blood flow MRI on large nonhuman primate retinas using a 3-Tesla clinical scanner as a first step toward translation. Baboon was chosen because of its evolutionary similarity to human. Anesthetized preparation, free of eye-movement artifacts, was used to evaluate clinical scanner hardware feasibility and optimize multimodal protocols for retinal MRI. Anatomical MRI (0.1 x 0.2 x 2.0 mm(3)) before contrast-agent injection detected three alternating bright-dark-bright layers. The hyperintense inner strip nearest to the vitreous was enhanced by an intravascular contrast agent, which likely included the ganglion and bipolar cell layer and the embedded retinal vessels. The hypointense middle strip showed no contrast enhancement, which likely included the avascular outer unclear layer and photoreceptor segments. The hyperintense outer strip showed contrast enhancement, which likely corresponded to the choroid vascular layer. In the posterior retina, the total thickness including the choroid was 617 +/-. 101 mu m ( standard deviation, n = 7). Blood oxygenation level-dependent functional MRI (0.3 x 0.6 x 2.0 mm(3)) of oxygen inhalation relative to air increased the signals by 6.5 +/- 1.4%. Basal blood flow (2 x 2 x 2 mm(3)) was 83 +/- 30 mL/100 g/min (air), and hypercapnia increased blood flow by 25 +/- 9% (P < 0.05). This study demonstrates multimodal MRI to image anatomy, physiology, and function on large nonhuman primate retinas using a clinical scanner, offering encouraging data to explore human applications. Magn Reson Med 66:546-554, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Zhang, Yi; Wey, Hsiao-Ying; Nateras, Oscar San Emeterio; Peng, Qi; De La Garza, Bryan H.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Zhang, Yi; Wey, Hsiao-Ying; Nateras, Oscar San Emeterio; Peng, Qi; De La Garza, Bryan H.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008; Wey, Hsiao-Ying/G-3031-2012 FU NIH/NEI [R01 EY014211, EY018855]; Department of Veterans Affairs; Translational Technology Research Grant via the Clinical Translational Science Award (CTSA) [UL1RR025767]; American Heart Association [EIA 0940104N] FX Grant sponsor: NIH/NEI; Grant numbers: R01 EY014211, EY018855; Grant sponsor: Department of Veterans Affairs; Grant sponsor: Translational Technology Research Grant via the Clinical Translational Science Award (CTSA); Grant number: UL1RR025767; Grant sponsor: American Heart Association's Established Investigator Award; Grant number: EIA 0940104N. NR 46 TC 5 Z9 5 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD AUG PY 2011 VL 66 IS 2 BP 546 EP 554 DI 10.1002/mrm.22853 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 799AV UT WOS:000293256800027 PM 21360746 ER PT J AU Tsai, PH Teng, E Liu, C Mendez, MF AF Tsai, Po-Heng Teng, Edmond Liu, Collin Mendez, Mario F. TI Posterior Cortical Atrophy: Evidence for Discrete Syndromes of Early-Onset Alzheimer's Disease SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Article DE posterior cortical atrophy; Alzheimer's disease; visual processing; visual agnosia; Balint syndrome; Gerstmann syndrome ID METABOLIC DEFICITS; DEMENTIA; MEMORY AB Background: Posterior cortical atrophy (PCA) may represent a discrete syndrome of Alzheimer's disease (AD) rather than amnestic AD with visual deficits. Methods: We separated 30 patients with PCA based on ventral and dorsal visual symptoms using cluster analysis and analyzed the demographic, cognitive, and functional imaging features. Results: This analysis revealed subgroups of 26 dorsal and 4 ventral patients. The ventral subgroup had greater confrontational naming impairment, and the dorsal subgroup had greater hypofunction in the parietal regions. The PCA cohort had memory retrieval rather than encoding deficits, and clinical follow-up showed relative isolation of dorsal and ventral visual manifestations. Conclusion: These results support 2, mostly nonoverlapping syndromes in patients with PCA, with the commonest affecting the dorsal visual pathway; moreover, the memory retrieval difficulty in the patients with PCA was dissimilar to the amnestic pattern in typical AD. These results suggest that, in most cases, PCA syndromes are discrete clinical variants of AD. C1 [Tsai, Po-Heng; Teng, Edmond; Liu, Collin; Mendez, Mario F.] W Los Angeles VA Healthcare Ctr, Neurobehavior Unit, Los Angeles, CA 90073 USA. [Tsai, Po-Heng; Teng, Edmond; Liu, Collin; Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Teng, Edmond] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. RP Tsai, PH (reprint author), W Los Angeles VA Healthcare Ctr, Neurobehavior Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM potsai@ucla.edu FU VA Special Fellowship for Geriatric Neurology; NIA [K08 AG 34628, R01AG034499-03]; AFAR [K08 AG 34628]; John A. Hartford Foundation [K08 AG 34628]; Atlantic Philanthropies [K08 AG 34628]; Starr Foundation [K08 AG 34628]; VA Merit Review FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: P-HT was supported by a VA Special Fellowship for Geriatric Neurology. ET is supported by K08 AG 34628 (jointly sponsored by NIA, AFAR, the John A. Hartford Foundation, the Atlantic Philanthropies, the Starr Foundation, and an anonymous donor). MFM is supported by a VA Merit Review and NIA R01AG034499-03. NR 24 TC 12 Z9 12 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-3175 J9 AM J ALZHEIMERS DIS JI Am. J. Alzheimers Dis. Other Dement. PD AUG PY 2011 VL 26 IS 5 BP 413 EP 418 DI 10.1177/1533317511418955 PG 6 WC Geriatrics & Gerontology; Clinical Neurology SC Geriatrics & Gerontology; Neurosciences & Neurology GA 836HQ UT WOS:000296102400009 PM 21831859 ER PT J AU Sherwood, JE Fraser, S Citron, DM Wexler, H Blakely, G Jobling, K Patrick, S AF Sherwood, Jeffrey E. Fraser, Susan Citron, Diane M. Wexler, Hana Blakely, Garry Jobling, Kelly Patrick, Sheila TI Multi-drug resistant Bacteroides fragilis recovered from blood and severe leg wounds caused by an improvised explosive device (IED) in Afghanistan SO ANAEROBE LA English DT Article DE Bacteroides fragilis; Multi-drug resistance; nimE; Plasmid; Linezolid ID METRONIDAZOLE RESISTANCE; MECHANISM; CFIA AB This report summarizes the case of a 23 year-old otherwise healthy male that was injured in an improvised explosive device (IED) blast in support of Operation Enduring Freedom (OEF). He sustained bilateral open tibia and fibula fractures in the setting of being exposed to water contaminated with raw sewage. Despite long-term carbapenem therapy, the patient's wounds were repeatedly noted to have purulent drainage during surgical debridement and cultures from these wounds were persistently positive for Bacteroides fragilis. Apparent clinical failure persisted despite the addition of metronidazole to his regimen and an eventual trial of tigecycline. Susceptibility testing of the B. fragilis isolate was performed and resistance to penicillin, clindamycin,metronidazole, cefoxitin, meropenem, imipenem, piperacillin/tazobactam, and tigecycline was confirmed. The presence of a nimE gene on a potentially transferrable plasmid was also confirmed by plasmid sequencing. The only antibiotics that displayed in vitro susceptibility were moxifloxacin and linezolid. These antibiotics were initiated in combination with aggressive irrigation and serial surgical debridement. Conversion to left-sided internal fixation became feasible and his left lower extremity was salvaged without residual evidence of infection. The patient completed an eight week course of combination moxifloxacin and linezolid therapy without adverse event. This B. fragilis isolate displayed simultaneous high-level resistance to multiple antibiotics routinely utilized in anaerobic infections. This was evidenced by clinical failure, in vitro susceptibility testing, and demonstration of genes associated with resistance mechanisms. This case warrants review not only due to the rarity of this event but also the potential implications regarding anaerobic infections in traumatic wounds and the success of a novel treatment regimen utilizing combination therapy with moxifloxacin and linezolid. Published by Elsevier Ltd. C1 [Sherwood, Jeffrey E.; Fraser, Susan] Walter Reed Army Med Ctr, Dept Infect Dis, Washington, DC 20307 USA. [Citron, Diane M.] RM Alden Res Lab, Culver City, CA 90230 USA. [Wexler, Hana] W Los Angeles VA Med Ctr, Los Angeles, CA 90076 USA. [Blakely, Garry; Jobling, Kelly] Univ Edinburgh, Inst Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland. [Patrick, Sheila] Queens Univ Belfast, Ctr Infect & Immun, Sch Med Dent & Biomed Sci, Belfast BT9 7BL, Antrim, North Ireland. RP Sherwood, JE (reprint author), Walter Reed Army Med Ctr, Dept Infect Dis, Ward 63,6900 Georgia Ave,NW, Washington, DC 20307 USA. EM jeffrey.e.sherwood@us.army.mil; susan.fraser@us.army.mil; d.m.citron@att.net; s.patrick@qub.ac.uk FU George-town University; R.M. Alden Research Laboratory; Walter Reed Army Medical Center FX The authors would like to thank Drs. Itzhak Brook of George-town University, Ellie J.C. Goldstein of the R.M. Alden Research Laboratory, and Gerald Van Horn of Walter Reed Army Medical Center for their contributions, support, and clinical input regarding this case. NR 18 TC 26 Z9 27 U1 3 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1075-9964 J9 ANAEROBE JI Anaerobe PD AUG PY 2011 VL 17 IS 4 SI SI BP 152 EP 155 DI 10.1016/j.anaerobe.2011.02.007 PG 4 WC Microbiology SC Microbiology GA 824ZF UT WOS:000295240000005 PM 21376821 ER PT J AU Li, XK Villard, JW Ouyang, YJ Michalek, JE Jabara, R Sims, D Kemp, N Glynn, T Banas, C Bailey, SR Feldman, MD AF Li, Xiankai Villard, Joseph W. Ouyang, Yongjian Michalek, Joel E. Jabara, Refat Sims, Dan Kemp, Nate Glynn, Tim Banas, Christopher Bailey, Steven R. Feldman, Marc D. TI Safety and efficacy of frequency domain optical coherence tomography in pigs SO EUROINTERVENTION LA English DT Article DE optical coherence tomography; safety; efficacy; frequency domain ID CORONARY STENT SYSTEM; NANOTHIN POLYZENE-F; ARTERY LESIONS; TRIAL; PLAQUES AB Aims: To determine the safety and efficacy of frequency domain OCT, which can scan at much higher rates and make it possible to avoid an occlusion balloon and image during an angiographic injection through guide catheter. The catheters have diameters ranging from 2.7 to 3.5 Fr. The presence of the imaging catheter increases fluid resistance to the injection of viscous solutions necessary for clearing the blood. Methods and results: The Volcano 3.5 Fr frequency domain OCT catheter system was investigated for safety in (a) n=10 porcine studies using acute and 30-day histology, and (b) for efficacy in n=9 in vivo porcine coronary arteries. We found: (a) frequency domain imaging is safe in the porcine model using histology as an endpoint; (b) the addition of a viscous contrast (iodixonal) to saline is superior for lumen clearance compared to saline alone; (c) hand injection, 4 ml/sec, and 6 ml/sec power injection all provided similar vessel wall clearance; (d) the anticipated loss of vessel wall visualisation with left main injection (due to half the injectate in the non-imaged vessel) was not evident in proximal and middle coronary artery OCT catheter positions. Conclusions: Frequency domain OCT is safe and efficacious in the porcine model. C1 [Li, Xiankai; Villard, Joseph W.; Bailey, Steven R.; Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, Janey Briscoe Div Cardiol, San Antonio, TX 78229 USA. [Li, Xiankai] Tongji Univ, Sch Med, Dept Cardiol, Shanghai Peoples Hosp 10, Shanghai 200092, Peoples R China. [Jabara, Refat] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel. [Jabara, Refat] St Josephs Translat Res Inst, Atlanta, GA USA. [Sims, Dan; Kemp, Nate; Glynn, Tim; Banas, Christopher] Volcano Corp, Billerica, MA USA. [Feldman, Marc D.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Feldman, MD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Janey Briscoe Div Cardiol, 7703 Floyd Curl Dr,Mail Code 7872, San Antonio, TX 78229 USA. EM feldmanm@uthscsa.edu FU Volcano Corporation, San Diego, CA, USA; VA Merit Grant FX This study was supported in part by Volcano Corporation, San Diego, CA, USA and a VA Merit Grant (MDF) NR 18 TC 2 Z9 2 U1 0 U2 1 PU EUROPA EDITION PI TOULOUSE CEDEX 6 PA 5, RUE SAINT-PANTALEON, BP 61508, TOULOUSE CEDEX 6, 31015, FRANCE SN 1774-024X J9 EUROINTERVENTION JI EuroIntervention PD AUG PY 2011 VL 7 IS 4 BP 497 EP 504 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 822EB UT WOS:000295025600014 PM 21764669 ER PT J AU Curtis, JR Baddley, JW Yang, S Patkar, N Chen, L Delzell, ES Mikuls, TR Saag, KG Singh, J Safford, M Cannon, GW AF Curtis, Jeffrey R. Baddley, John W. Yang, Shuo Patkar, Nivedita Chen, Lang Delzell, Elizabeth S. Mikuls, Ted R. Saag, Kenneth G. Singh, Jasvinder Safford, Monika Cannon, Grant W. TI Validation of a Preliminary Administrative Claims-Based Algorithm for the Effectiveness of Medications for Rheumatoid Arthritis SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Curtis, Jeffrey R.; Baddley, John W.; Yang, Shuo; Patkar, Nivedita; Chen, Lang; Delzell, Elizabeth S.; Saag, Kenneth G.; Singh, Jasvinder; Safford, Monika] Univ Alabama, Birmingham, AL USA. [Baddley, John W.; Singh, Jasvinder] Birmingham VA Med Ctr, Birmingham, AL USA. [Mikuls, Ted R.] Omaha VA Med Ctr, Omaha, NE USA. [Mikuls, Ted R.] Univ Nebraska, Med Ctr, Omaha, NE USA. [Cannon, Grant W.] George E Wahlen VA Med Ctr, Salt Lake City, UT USA. [Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. RI YANG, SHUO/D-2695-2014 OI YANG, SHUO/0000-0002-4999-0506 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 161 BP S69 EP S70 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600156 ER PT J AU Lavigne, JE Au, A Rong, J Wang, Y Good, CB Glassman, PA Cunningham, F AF Lavigne, Jill E. Au, Anthony Rong, Jiang Wang, Yu Good, C. B. Glassman, Peter A. Cunningham, Francesca TI Utilization of Prescription Drugs with Warnings of Suicidal Thoughts and Behaviors in the US and the US Department of Veterans Affairs (VA), 2009 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Lavigne, Jill E.] US Dept Vet Affairs, Pharm Benefit Management Grp, Ctr Excellence Suicide Prevent, Canandaigua, NY USA. [Lavigne, Jill E.] St John Fisher Coll, Wegmans Sch Pharm, Rochester, NY 14618 USA. [Au, Anthony; Rong, Jiang; Wang, Yu; Good, C. B.; Cunningham, Francesca] US Dept Vet Affairs, Pharm Benefits Management Serv Ctr Med Safety VAM, Hines, IL USA. [Good, C. B.] Pittsburgh Healthcare Syst, Dept Vet Affairs, Pittsburgh, PA USA. [Glassman, Peter A.] Greater Angeles Healthcare Syst, Dept Vet Affairs, Los Angeles, CA USA. [Good, C. B.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 496 BP S216 EP S217 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600479 ER PT J AU Marcum, ZA Amuan, ME Hanlon, JT Aspinall, SL Handler, SM Ruby, CM Pugh, MJV AF Marcum, Zachary A. Amuan, Megan E. Hanlon, Joseph T. Aspinall, Sherrie L. Handler, Steven M. Ruby, Christine M. Pugh, Mary Jo V. TI Therapeutic Failures and Adverse Drug Withdrawal Events Leading to Hospitalization among Older Outpatient Veterans SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Marcum, Zachary A.; Hanlon, Joseph T.; Aspinall, Sherrie L.; Handler, Steven M.; Ruby, Christine M.] Univ Pittsburgh, Pittsburgh, PA USA. [Marcum, Zachary A.; Hanlon, Joseph T.; Handler, Steven M.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Amuan, Megan E.] Bedford VA Hosp, Bedford, MA USA. [Hanlon, Joseph T.; Aspinall, Sherrie L.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Aspinall, Sherrie L.] VA Pharm Benefits Management Serv, VA Ctr Medicat Safety, Hines, IL USA. [Aspinall, Sherrie L.] S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX 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 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 692 BP S300 EP S301 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600665 ER PT J AU Williams, JR Crentsil, V Duncan, L Goldstein, S Graham, D Hammer, M Kavanagh, J Kornegay, C Levin, R Weintraub, D Wilkinson, J Kales, H AF Williams, James R. Crentsil, Victor Duncan, Laurie Goldstein, Susanne Graham, David Hammer, Marlene Kavanagh, Janet Kornegay, Cynthia Levin, Robert Weintraub, Daniel Wilkinson, Jayne Kales, Helen TI Retrospective Method To Identify Tardive Dyskinesia in Electronic Medical Records SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Williams, James R.; Kornegay, Cynthia] US FDA, Div Epidemiol, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD USA. [Crentsil, Victor; Duncan, Laurie; Levin, Robert] US FDA, Div Psychiat Prod, Ctr Drug Evaluat & Res, Off New Drugs,Off Drug Evaluat 1, Silver Spring, MD USA. [Goldstein, Susanne] US FDA, Div Neurol Prod, Ctr Drug Evaluat & Res, Off New Drugs,Off Drug Evaluat 1, Silver Spring, MD USA. [Graham, David; Hammer, Marlene] US FDA, Immediate Off, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD USA. [Kavanagh, Janet; Kales, Helen] Ann Arbor Ctr Excellence, Serious Mental Illness Treatment Res & Evaluat Ct, Dept Vet Affairs, Ann Arbor, MI USA. [Kavanagh, Janet; Kales, Helen] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Weintraub, Daniel; Wilkinson, Jayne] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Dept Vet Affairs, Philadelphia, PA USA. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Wilkinson, Jayne] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 807 BP S348 EP S349 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600772 ER PT J AU Winthrop, KL Baxter, R Liu, LY McFarland, B Austin, DF Varley, CD Radcliffe, L Suhler, EB Choi, D Rosenbaum, JT Herrinton, LJ AF Winthrop, Kevin L. Baxter, Roger Liu, Liyan McFarland, Bentson Austin, Donald F. Varley, Cara D. Radcliffe, LeAnn Suhler, Eric B. Choi, Dongseok Rosenbaum, James T. Herrinton, Lisa J. TI Mycobacterial Disease in Patients Who Use Anti-Tumor Necrosis Factor Therapy SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Winthrop, Kevin L.; McFarland, Bentson; Austin, Donald F.; Varley, Cara D.; Suhler, Eric B.; Choi, Dongseok; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Baxter, Roger; Liu, Liyan; Herrinton, Lisa J.] Kaiser Permanente No Calif, Oakland, CA USA. [Winthrop, Kevin L.; Austin, Donald F.; Radcliffe, LeAnn; Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 198 BP S86 EP S86 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600192 ER PT J AU Arif, SA Poon, H AF Arif, Sally A. Poon, Henry TI Tadalafil: A Long-Acting Phosphodiesterase-5 Inhibitor for the Treatment of Pulmonary Arterial Hypertension SO CLINICAL THERAPEUTICS LA English DT Review DE phosphodiesterase-5 inhibitor; pulmonary arterial hypertension; tadalafil ID HEALTHY MALE-SUBJECTS; QUALITY-OF-LIFE; SILDENAFIL; THERAPY; PHARMACOKINETICS; DYSFUNCTION; RESPONSES; BOSENTAN; SURVIVAL; BLOCKERS AB Background: Tadalafil is a phosphodiesterase-5 (PDE-5) inhibitor that was approved by the US Food and Drug Administration (FDA) in 2009 for the treatment of pulmonary arterial hypertension (PAH). Objective: The purpose of this review is to evaluate the pharmacology, pharmacokinetic properties, clinical efficacy, adverse effects, drug interactions, and dosage and administration of tadalafil in patients with PAH. Methods: A literature search of MEDLINE and International Pharmaceutical Abstracts (1960 through September 5, 2010) was conducted with the search terms tadalafil, pulmonary arterial hypertension, and phosphodiesterase-5 inhibitor. Data found from orignial research and case series published in English were screened for relevancy to pharmacology, pharmacokinetics, clinical efficacy and safety, and tolerability. Relevant articles from the bibliographies of the identified published articles were also obtained. Unpublished data and posters were obtained from the manufacturer of tadalafil and the FDA Web site. Results: By selectively inhibiting PDE-5, tadalafil causes nitric oxide mediated vasodilation in the pulmonary vasculature. Tadalafil has a greater affinity (10,000-fold) for PDE-5 compared with the other PDE inhibitors and has a t(1/2) of 17.5 hours. In a controlled clinical study in patients with PAH, patients receiving tadalafil in a total daily dose of 40 mg had significant improvements in their 6-minute walk distance (33 m from baseline) and time to clinical worsening compared with those receiving placebo (both, P < 0.05). Tadalafil had adverse effects similar to placebo, with headache being the most commonly reported (42%). Conclusions: In the small number of studies available, tadalafil was effective and well tolerated when used to treat patients with PAH. Compared with placebo, tadalafil was associated with significant improvements in exercise capacity and reduced time to clinical worsening (68% relative risk reduction; P = 0.038). There is limited evidence comparing tadalafil with sildenafil and vardenafil, and the studies are limited by short treatment durations. (Clin Ther. 2011;33: 993-1004) (C) 2011 Elsevier HS Journals, Inc. All rights reserved. Key C1 [Arif, Sally A.] Midwestern Univ, Chicago Coll Pharm, Dept Pharm Practice, Downers Grove, IL 60515 USA. [Arif, Sally A.] Rush Univ, Dept Pharm, Med Ctr, Chicago, IL 60612 USA. [Poon, Henry] James J Peters VA Med Ctr, Dept Pharm, Bronx, NY USA. RP Arif, SA (reprint author), Midwestern Univ, Chicago Coll Pharm, Dept Pharm Practice, 555 31st St, Downers Grove, IL 60515 USA. EM sarif@midwestern.edu RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 48 TC 16 Z9 18 U1 0 U2 7 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD AUG PY 2011 VL 33 IS 8 BP 993 EP 1004 DI 10.1016/j.clinthera.2011.06.008 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 818KE UT WOS:000294749800001 PM 21762988 ER PT J AU Laiteerapong, N Karter, AJ Liu, JY Moffet, HH Sudore, R Schillinger, D John, PM Huang, ES AF Laiteerapong, Neda Karter, Andrew J. Liu, Jennifer Y. Moffet, Howard H. Sudore, Rebecca Schillinger, Dean John, Priya M. Huang, Elbert S. TI Correlates of Quality of Life in Older Adults With Diabetes The Diabetes & Aging Study SO DIABETES CARE LA English DT Article ID GERIATRIC SYNDROMES; SELF-MANAGEMENT; PRIMARY-CARE; CHRONIC-PAIN; HEALTH; ASSOCIATION; DISPARITIES; RETIREMENT; COMMUNITY; DISEASES AB OBJECTIVE-To evaluate associations between health-related quality of life (HRQL) and geriatric syndromes, diabetes complications, and hypoglycemia in older adults with diabetes. RESEARCH DESIGN AND METHODS-A race-stratified random sample of 6,317 adults with type 2 or type 1 diabetes, aged 60 to 75 years, enrolled in Kaiser Permanente Northern California, who completed a survey that included a HRQL instrument based on the Short Form 8-item health survey. Administrative records were used to ascertain diagnoses of geriatric syndromes, diabetes complications, and hypoglycemia. Associations were estimated between HRQL and exposures in exposure-specific and combined exposure models (any syndrome, any complication, or hypoglycemia). Conservatively, differences of points were considered the minimally important difference in HRQL scores. RESULTS-HRQL was lower with nearly all exposures of interest. The lowest physical HRQL was associated with amputation. In combined exposure models, geriatric syndromes (-5.3 [95% CI -5.8 to -4.8], P < 0.001) and diabetes complications (-3.5 [-4.0 to -2.9], P < 0.001) were associated with lower physical HRQL. The lowest mental HRQL was associated with depression, underweight (BMI <18 kg/m(2)), amputation, and hypoglycemia. In combined exposure models, only hypoglycemia was associated with lower mental HRQL (-4.0[-7.0 to 1.1], P = 0.008). CONCLUSIONS-Geriatric syndromes and hypoglycemia are associated with lower HRQL to a comparable degree as diabetes complications. Addressing geriatric syndromes and avoiding hypoglycemia should be given as high a priority as preventing diabetes complications in older adults with diabetes. C1 [Laiteerapong, Neda; John, Priya M.; Huang, Elbert S.] Univ Chicago, Dept Med, Gen Internal Med Sect, Chicago, IL 60637 USA. [Karter, Andrew J.; Liu, Jennifer Y.; Moffet, Howard H.] Kaiser Permanente, Div Res, Oakland, CA USA. [Sudore, Rebecca] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Sudore, Rebecca] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Schillinger, Dean] Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94143 USA. [Schillinger, Dean] Univ Calif San Francisco, San Francisco Gen Hosp, Ctr Vulnerable Populat, San Francisco, CA 94143 USA. [Schillinger, Dean] Calif Diabet Program, Calif Dept Publ Hlth, Sacramento, CA USA. RP Laiteerapong, N (reprint author), Univ Chicago, Dept Med, Gen Internal Med Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM nlaiteer@medicine.bsd.uchicago.edu FU National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01-DK-081796, RC1-DK-086178, R01-DK-080726, R01-DK-065664]; National Institute of Child Health and Human Development [R01-HD-46113]; Agency for Healthcare Research and Quality [T32-HS000084]; NIDDK [F32-DK-089973]; NIDDK Diabetes and Research Training Center at the University of Chicago [P60-DK-20595]; NIH [UL1-RR-024131]; Centers for Disease Control and Prevention [1U58-DP-002007-02] FX This work was performed with support by the National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; grants R01-DK-081796, RC1-DK-086178, R01-DK-080726, R01-DK-065664), and the National Institute of Child Health and Human Development (grant R01-HD-46113). N.L. was supported by the Agency for Healthcare Research and Quality (T32-HS000084) and the NIDDK (F32-DK-089973). N.L., P.M.J., and E.S.H. are members of the NIDDK Diabetes and Research Training Center at the University of Chicago (grant P60-DK-20595). D.S. was supported by the NIH Clinical and Translational Sciences Award (grant UL1-RR-024131) and the Centers for Disease Control and Prevention (grant 1U58-DP-002007-02). NR 26 TC 51 Z9 55 U1 1 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2011 VL 34 IS 8 BP 1749 EP 1753 DI 10.2337/dc10-2424 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 809EU UT WOS:000294035400013 PM 21636795 ER PT J AU Ram, R Storb, R Sandmaier, BM Maloney, DG Woolfrey, A Flowers, MED Maris, MB Laport, GG Chauncey, TR Lange, T Langston, AA Storer, B Georges, GE AF Ram, Ron Storb, Rainer Sandmaier, Brenda M. Maloney, David G. Woolfrey, Ann Flowers, Mary E. D. Maris, Michael B. Laport, Ginna G. Chauncey, Thomas R. Lange, Thoralf Langston, Amelia A. Storer, Barry Georges, George E. TI Non-myeloablative conditioning with allogeneic hematopoietic cell transplantation for the treatment of high-risk acute lymphoblastic leukemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE acute lymphoblastic leukemia; Philadelphia chromosome-positive; allogeneic hematopoietic cell transplantation; non-myeloablative conditioning; imatinib ID 1ST COMPLETE REMISSION; ACUTE LYMPHOCYTIC-LEUKEMIA; VERSUS-HOST-DISEASE; TOTAL-BODY IRRADIATION; TERM-FOLLOW-UP; ADULT PATIENTS; HYPER-CVAD; HEMATOLOGIC MALIGNANCIES; IMATINIB MESYLATE; MYCOPHENOLATE-MOFETIL AB Background Allogeneic hematopoietic cell transplantation is a potentially curative treatment for patients with acute lymphoblastic leukemia. However, the majority of older adults with acute lymphoblastic leukemia are not candidates for myeloablative conditioning regimens. A non-myeloablative preparative regimen is a reasonable treatment option for this group. We sought to determine the outcome of non-myeloablative conditioning and allogeneic transplantation in patients with high-risk acute lymphoblastic leukemia. Design and Methods Fifty-one patients (median age 56 years) underwent allogeneic hematopoietic cell transplantation from sibling or unrelated donors after fludarabine and 2 Gray total body irradiation. Twenty-five patients had Philadelphia chromosome-positive acute lymphoblastic leukemia. Eighteen of these patients received post-grafting imatinib. Results With a median follow-up of 43 months, the 3-year overall survival was 34%. The 3-year relapse/progression and non-relapse mortality rates were 40% and 28%, respectively. The cumulative incidences of grades II and III-IV acute graft-versus-host disease were 53% and 6%, respectively. The cumulative incidence of chronic graft-versus-host disease was 44%. Hematopoietic cell transplantation in first complete remission and post-grafting imatinib were associated with improved survival (P=0.005 and P=0.03, respectively). Three-year overall survival rates for patients with Philadelphia-negative acute lymphoblastic leukemia in first remission and beyond first remission were 52% and 8%, respectively. For patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in first remission who received post-grafting imatinib, the 3-year overall survival rate was 62%; for the subgroup without evidence of minimal residual disease at transplantation, the overall survival was 73%. Conclusions For patients with high-risk acute lymphoblastic leukemia in first complete remission, non-myeloablative conditioning and allogeneic hematopoietic cell transplantation, with post-grafting imatinib for Philadelphia chromosome-positive disease, can result in favorable long-term survival. (Clinicaltrials.gov identifier: NCT0036738) C1 [Ram, Ron; Storb, Rainer; Sandmaier, Brenda M.; Maloney, David G.; Woolfrey, Ann; Flowers, Mary E. D.; Storer, Barry; Georges, George E.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Storb, Rainer; Sandmaier, Brenda M.; Maloney, David G.; Woolfrey, Ann; Flowers, Mary E. D.; Chauncey, Thomas R.; Storer, Barry; Georges, George E.] Univ Washington, Sch Med, Seattle, WA USA. [Maris, Michael B.] Rocky Mt Canc Ctr, Denver, CO USA. [Laport, Ginna G.] Stanford Univ, Stanford, CA 94305 USA. [Chauncey, Thomas R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Lange, Thoralf] Univ Leipzig, Leipzig, Germany. [Langston, Amelia A.] Emory Univ, Atlanta, GA 30322 USA. RP Georges, GE (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D1-100, Seattle, WA 98109 USA. EM ggeorges@fhcrc.org FU National Institutes of Health, Bethesda, MD [P01CA018029, P01CA078902, P30CA015704]; Davidoff Foundation FX this work was supported by grants from the National Institutes of Health, Bethesda, MD (grants P01CA018029, P01CA078902, and P30CA015704). RR was a recipient of a fellowship award from the Davidoff Foundation. NR 41 TC 49 Z9 52 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD AUG PY 2011 VL 96 IS 8 BP 1113 EP 1120 DI 10.3324/haematol.2011.040261 PG 8 WC Hematology SC Hematology GA 818BA UT WOS:000294722700008 PM 21508120 ER PT J AU Hempel, S Rubenstein, LV Shanman, RM Foy, R Golder, S Danz, M Shekelle, PG AF Hempel, Susanne Rubenstein, Lisa V. Shanman, Roberta M. Foy, Robbie Golder, Su Danz, Marjorie Shekelle, Paul G. TI Identifying quality improvement intervention publications - A comparison of electronic search strategies SO IMPLEMENTATION SCIENCE LA English DT Article ID HEALTH-CARE; CONTROLLED-TRIALS; PALLIATIVE CARE; RELEVANT; MEDLINE; FILTER AB Background: The evidence base for quality improvement (QI) interventions is expanding rapidly. The diversity of the initiatives and the inconsistency in labeling these as QI interventions makes it challenging for researchers, policymakers, and QI practitioners to access the literature systematically and to identify relevant publications. Methods: We evaluated search strategies developed for MEDLINE (Ovid) and PubMed based on free text words, Medical subject headings (MeSH), QI intervention components, continuous quality improvement (CQI) methods, and combinations of the strategies. Three sets of pertinent QI intervention publications were used for validation. Two independent expert reviewers screened publications for relevance. We compared the yield, recall rate, and precision of the search strategies for the identification of QI publications and for a subset of empirical studies on effects of QI interventions. Results: The search yields ranged from 2,221 to 216,167 publications. Mean recall rates for reference publications ranged from 5% to 53% for strategies with yields of 50,000 publications or fewer. The 'best case' strategy, a simple text word search with high face validity ('quality' AND 'improv*' AND 'intervention*') identified 44%, 24%, and 62% of influential intervention articles selected by Agency for Healthcare Research and Quality (AHRQ) experts, a set of exemplar articles provided by members of the Standards for Quality Improvement Reporting Excellence (SQUIRE) group, and a sample from the Cochrane Effective Practice and Organization of Care Group (EPOC) register of studies, respectively. We applied the search strategy to a PubMed search for articles published in 10 pertinent journals in a three-year period which retrieved 183 publications. Among these, 67% were deemed relevant to QI by at least one of two independent raters. Forty percent were classified as empirical studies reporting on a QI intervention. Conclusions: The presented search terms and operating characteristics can be used to guide the identification of QI intervention publications. Even with extensive iterative development, we achieved only moderate recall rates of reference publications. Consensus development on QI reporting and initiatives to develop QI-relevant MeSH terms are urgently needed. C1 [Hempel, Susanne; Rubenstein, Lisa V.; Shanman, Roberta M.; Danz, Marjorie; Shekelle, Paul G.] RAND Corp, Santa Monica, CA 90407 USA. [Rubenstein, Lisa V.; Shekelle, Paul G.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Rubenstein, Lisa V.; Shekelle, Paul G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Foy, Robbie] Univ Leeds, Leeds LS2 9JT, W Yorkshire, England. [Golder, Su] Univ York, Ctr Reviews & Disseminat, York YO10 5DD, N Yorkshire, England. RP Hempel, S (reprint author), RAND Corp, Santa Monica, CA 90407 USA. EM susanne_hempel@rand.org OI Kimmel, Ellen K./0000-0002-6473-9491; golder, su/0000-0002-8987-5211 FU RAND Corporation; Veterans Affairs Greater Los Angeles Healthcare System; Robert Wood Johnson Foundation [65113] FX We would like to thank Jeremy Grimshaw and the Cochrane Effective Practice and Organization of Care Group (EPOC) for providing a search strategy and access to the database of registered quality improvement initiative; Greg Ogrinc, Paul Batalden, Seth Landefield, Julia Neily and Frank Davidoff as members of the SQUIRE group for providing us with a selection of pertinent quality improvement publications; Ellen Kimmel, Susanne Salem-Schatz and Heather Woodward-Hagg for assistance with the search strategies, Nancy Wilczynski and Carl Patow for comments on earlier drafts of the manuscript, Breanne Johnsen for assistance in the project and manuscript preparation and Sydne Newberry for manuscript editing. The project was funded by the RAND Corporation, the Veterans Affairs Greater Los Angeles Healthcare System and in parts through a grant from the Robert Wood Johnson Foundation (ID 65113). NR 28 TC 13 Z9 13 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD AUG 1 PY 2011 VL 6 AR 85 DI 10.1186/1748-5908-6-85 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 819GB UT WOS:000294812300001 PM 21806808 ER PT J AU Sattin, A Pekary, AE Blood, J AF Sattin, Albert Pekary, Albert Eugene Blood, James TI Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by prazosin SO PEPTIDES LA English DT Article DE Post-traumatic stress disorder; Thyrotropin releasing hormone; Limbic system ID POSTTRAUMATIC-STRESS-DISORDER; AUTONOMIC NERVOUS-SYSTEM; HORMONE TRH; INSULIN-SECRETION; COMBAT VETERANS; IN-VITRO; NOREPINEPHRINE; ACTIVATION; DEPRESSION; PANCREAS AB Hyperresponsiveness to norepinephrine contributes to post-traumatic stress disorder (PTSD). Prazosin, a brain-active blocker of alpha(1)-adrenoceptors, originally used for the treatment of hypertension, has been reported to alleviate trauma nightmares, sleep disturbance and improve global clinical status in war veterans with PTSD. Thyrotropin-releasing hormone (TRH, pGIu-His-Pro-NH(2)) may play a role in the pathophysiology and treatment of neuropsychiatric disorders such as major depression, and PTSD (an anxiety disorder). To investigate whether TRH or TRH-like peptides (pGlu-X-Pro-NH(2), where "X" can be any amino acid residue) participate in the therapeutic effects of prazosin, male rats were injected with prazosin and these peptides then measured in brain and endocrine tissues. Prazosin stimulated TRH and TRH-like peptide release in those tissues with high alpha(1)-adrenoceptor levels suggesting that these peptides may play a role in the therapeutic effects of prazosin. Published by Elsevier Inc. C1 [Sattin, Albert; Pekary, Albert Eugene; Blood, James] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. [Sattin, Albert] VA Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA 90073 USA. [Sattin, Albert] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90073 USA. [Sattin, Albert] Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA 90073 USA. [Pekary, Albert Eugene] VA Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ, Los Angeles, CA 90073 USA. [Sattin, Albert] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. [Pekary, Albert Eugene] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Pekary, AE (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv, Bldg 114,Rm 229,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jpekary@yahoo.com RI Schueter, nicos/A-3625-2014 FU Veterans Administration; Pekary Family Trust FX This work was supported by Veterans Administration Medical Research Funds (AEP and AS) and the Pekary Family Trust. NR 65 TC 5 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 0196-9781 J9 PEPTIDES JI Peptides PD AUG PY 2011 VL 32 IS 8 BP 1666 EP 1676 DI 10.1016/j.peptides.2011.06.012 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 816BD UT WOS:000294572800015 PM 21718733 ER PT J AU Hamza, TH Chen, HL Hill-Burns, EM Rhodes, SL Montimurro, J Kay, DM Tenesa, A Kusel, VI Sheehan, P Eaaswarkhanth, M Yearout, D Samii, A Roberts, JW Agarwal, P Bordelon, Y Park, Y Wang, LY Gao, JJ Vance, JM Kendler, KS Bacanu, SA Scott, WK Ritz, B Nutt, J Factor, SA Zabetian, CP Payami, H AF Hamza, Taye H. Chen, Honglei Hill-Burns, Erin M. Rhodes, Shannon L. Montimurro, Jennifer Kay, Denise M. Tenesa, Albert Kusel, Victoria I. Sheehan, Patricia Eaaswarkhanth, Muthukrishnan Yearout, Dora Samii, Ali Roberts, John W. Agarwal, Pinky Bordelon, Yvette Park, Yikyung Wang, Liyong Gao, Jianjun Vance, Jeffery M. Kendler, Kenneth S. Bacanu, Silviu-Alin Scott, William K. Ritz, Beate Nutt, John Factor, Stewart A. Zabetian, Cyrus P. Payami, Haydeh TI Genome-Wide Gene-Environment Study Identifies Glutamate Receptor Gene GRIN2A as a Parkinson's Disease Modifier Gene via Interaction with Coffee SO PLOS GENETICS LA English DT Article ID RISK-FACTORS; ASSOCIATION; SMOKING; CAFFEINE; MODEL; TRIAL; ONSET; ISTRADEFYLLINE; METAANALYSIS; VARIANTS AB Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P(2df)=10(-6), GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6x10(-7)) but not in light coffee-drinkers. The a priori Replication hypothesis that "Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers" was confirmed: OR(Replication) = 0.59, P(Replication) = 10(-3); OR(Pooled) = 0.51, P(Pooled) = 7x10(-8). Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3x10(-3)), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6x10(-13)). Imputation revealed a block of SNPs that achieved P(2df)<5x10(-8) in GWAIS, and OR = 0.41, P = 3x10(-8) in heavy coffee-drinkers. This study is proof of concept that inclusion of environmental factors can help identify genes that are missed in GWAS. Both adenosine antagonists (caffeine-like) and glutamate antagonists (GRIN2A-related) are being tested in clinical trials for treatment of PD. GRIN2A may be a useful pharmacogenetic marker for subdividing individuals in clinical trials to determine which medications might work best for which patients. C1 [Hamza, Taye H.; Hill-Burns, Erin M.; Montimurro, Jennifer; Kay, Denise M.; Kusel, Victoria I.; Sheehan, Patricia; Eaaswarkhanth, Muthukrishnan; Yearout, Dora; Payami, Haydeh] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Chen, Honglei; Gao, Jianjun] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Rhodes, Shannon L.; Ritz, Beate] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Tenesa, Albert] Univ Edinburgh, Roslin Inst, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Yearout, Dora; Samii, Ali; Zabetian, Cyrus P.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Yearout, Dora; Samii, Ali; Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Roberts, John W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Agarwal, Pinky] Evergreen Hosp, Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. [Bordelon, Yvette; Ritz, Beate] Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. [Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol, Bethesda, MD 20892 USA. [Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Genet, Bethesda, MD 20892 USA. [Wang, Liyong; Vance, Jeffery M.; Scott, William K.] Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL 33136 USA. [Wang, Liyong; Vance, Jeffery M.; Scott, William K.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Gen, Miami, FL 33136 USA. [Kendler, Kenneth S.; Bacanu, Silviu-Alin] Virginia Commonwealth Univ, Dept Psychiat, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Ritz, Beate] Univ Calif Los Angeles, Sch Publ Hlth, Ctr Occupat & Environm Hlth, Dept Environm Hlth Sci, Los Angeles, CA 90024 USA. [Nutt, John] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Hamza, TH (reprint author), New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. EM hpayami@wadsworth.org RI Ritz, Beate/E-3043-2015 OI Kay, Denise/0000-0002-9928-2698; Zabetian, Cyrus/0000-0002-7739-4306; Eaaswarkhanth, Muthukrishnan/0000-0001-9631-8555; Chen, Honglei/0000-0003-3446-7779; Park, Yikyung/0000-0002-6281-489X FU National Institute of Neurological Disorders and Stroke (NINDS) [R01 NS36960, R01 NS067469]; Michael J. Fox Foundation; Department of Veterans Affairs [1I01BX000531]; Close to a Cure Foundation, Research of Foundation for the Carolinas; National Institutes of Health [HHSN268200782096C]; National Institute of Environmental Health Sciences (NIEHS) [R01 ES010544, P01 ES016732]; UCLA Center for Neurodegeneration Science; NINDS [P50 NS038367, P50 NS039764]; NIEHS [Z01-ES-101986]; National Cancer Institute [Z01 CP010196-02] FX NGRC was supported by grants from the National Institute of Neurological Disorders and Stroke (NINDS) R01 NS36960 and R01 NS067469 (http://www.ninds.nih.gov/) and from the Michael J. Fox Foundation (Edmond J. Safra Global Genetics Consortia) (http://www.michaeljfox.org/). Additional support for subject recruitment was provided by the Department of Veterans Affairs (1I01BX000531) and The Close to a Cure Foundation: A Fund for Parkinson's Research of Foundation for the Carolinas. Genome-wide genotyping was performed at CIDR and funded by the National Institutes of Health (HHSN268200782096C). The PEG study was funded by National Institute of Environmental Health Sciences (NIEHS R01 ES010544 and P01 ES016732), UCLA Center for Neurodegeneration Science, and NINDS (P50 NS038367). The PAGE study was supported by NIEHS (Z01-ES-101986) and the National Cancer Institute (Z01 CP010196-02). HIHG was supported by NINDS (P50 NS039764). Some of the HIHG samples were collected while JMV and WKS were faculty members at Duke University. 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 52 TC 83 Z9 83 U1 2 U2 28 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 AUG PY 2011 VL 7 IS 8 AR e1002237 DI 10.1371/journal.pgen.1002237 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 812MG UT WOS:000294297000032 PM 21876681 ER PT J AU Marroquin, OC Weisbord, S AF Marroquin, Oscar C. Weisbord, Steven TI Cardiovascular Evaluation before Renal Transplantation: To Cath or Not to Cath? SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID MAJOR VASCULAR-SURGERY; MYOCARDIAL-INFARCTION; KIDNEY-TRANSPLANTATION; DISEASE; TRIAL C1 [Marroquin, Oscar C.] Div Cardiol, Pittsburgh, PA 15224 USA. [Marroquin, Oscar C.] UPMC Ctr Heart & Vasc Qual Outcomes & Clin Res, Pittsburgh, PA USA. [Weisbord, Steven] Univ Pittsburgh, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Marroquin, Oscar C.] Univ Pittsburgh, Med Ctr, Heart & Vasc Ctr Qual Outcomes Clin Res, Pittsburgh, PA USA. [Weisbord, Steven] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Weisbord, Steven] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Marroquin, OC (reprint author), Div Cardiol, Pittsburgh, PA 15224 USA. RI Marroquin, Oscar/F-2214-2015 OI Marroquin, Oscar/0000-0002-0909-0319 NR 13 TC 0 Z9 0 U1 0 U2 0 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 AUG PY 2011 VL 6 IS 8 BP 1807 EP 1809 DI 10.2215/CJN.06420611 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 805IZ UT WOS:000293721400002 PM 21784833 ER PT J AU Srisawat, N Wen, XY Lee, M Kong, L Elder, M Carter, M Unruh, M Finkel, K Vijayan, A Ramkumar, M Paganini, E Singbartl, K Palevsky, PM Kellum, JA AF Srisawat, Nattachai Wen, Xiaoyan Lee, MinJae Kong, Lan Elder, Michele Carter, Melinda Unruh, Mark Finkel, Kevin Vijayan, Anitha Ramkumar, Mohan Paganini, Emil Singbartl, Kai Palevsky, Paul M. Kellum, John A. TI Urinary Biomarkers and Renal Recovery in Critically Ill Patients with Renal Support SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE KIDNEY INJURY; HEPATOCYTE GROWTH-FACTOR; GELATINASE-ASSOCIATED LIPOCALIN; EARLY PREDICTIVE BIOMARKER; INTENSIVE-CARE-UNIT; CYSTATIN-C; REPLACEMENT THERAPY; ADVERSE OUTCOMES; CARDIAC-SURGERY; EARLY MARKER AB Background and objectives Despite significant advances in the epidemiology of acute kidney injury (AKI), prognostication remains a major clinical challenge. Unfortunately, no reliable method to predict renal recovery exists. The discovery of biomarkers to aid in clinical risk prediction for recovery after AKI would represent a significant advance over current practice. Design, setting, participants, & measurements We conducted the Biological Markers of Recovery for the Kidney study as an ancillary to the Acute Renal Failure Trial Network study. Urine samples were collected on days 1, 7, and 14 from 76 patients who developed AM and received renal replacement therapy (RRT) in the intensive care unit. We explored whether levels of urinary neutrophil gelatinase-associated lipocalin (uN-GAL), urinary hepatocyte growth factor (uHGF), urinary cystatin C (uCystatin C), IL-18, neutrophil gelatinase-associated lipocalin/matrix metalloproteinase-9, and urine creatinine could predict subsequent renal recovery. Results We defined renal recovery as alive and free of dialysis at 60 days from the start of RRT. Patients who recovered had higher uCystatin C on day 1 (7.27 versus 6.60 ng/mg(center dot)creatinine) and lower uHGF on days 7 and 14 (2.97 versus 3.48 ng/mg(center dot)creatinine; 2.24 versus 3.40 ng/mg(center dot)creatinine). For predicting recovery, decreasing uNGAL and uHGF in the first 14 days was associated with greater odds of renal recovery. The most predictive model combined relative changes in biomarkers with clinical variables and resulted in an area under the receiver-operator characteristic curve of 0.94. Conclusions We showed that a panel of urine biomarkers can augment clinical risk prediction for recovery after AKI. Clin J Am Soc Nephrol 6: 1815-1823, 2011. doi: 10.2215/CJN.11261210 C1 [Srisawat, Nattachai; Wen, Xiaoyan; Lee, MinJae; Kong, Lan; Elder, Michele; Carter, Melinda; Unruh, Mark; Singbartl, Kai; Palevsky, Paul M.; Kellum, John A.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, CRISMA Clin Res Invest & Syst Modeling Acute Illn, Pittsburgh, PA 15261 USA. [Unruh, Mark; Ramkumar, Mohan; Palevsky, Paul M.; Kellum, John A.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15261 USA. [Lee, MinJae; Kong, Lan] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Finkel, Kevin] Univ Texas Houston, Sch Med, Dept Med, Div Renal Dis & Hypertens, Houston, TX 77030 USA. [Vijayan, Anitha] Washington Univ, Dept Med, Div Renal Dis, St Louis, MO USA. [Ramkumar, Mohan; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15261 USA. [Ramkumar, Mohan; Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Paganini, Emil] Cleveland Clin Fdn, Dept Hypertens & Nephrol, Cleveland, OH 44195 USA. RP Kellum, JA (reprint author), Univ Pittsburgh, Sch Med, Dept Crit Care Med, CRISMA Clin Res Invest & Syst Modeling Acute Illn, 604 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM kellumja@ccm.upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01DK070910, Y1-DK-3508-01]; Department of Veterans Affairs Office of Research and Development [530] FX BioMaRK was supported by a grant (R01DK070910) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of NIDDK or NIH. The VA/NIH ATN study was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development (CSP #530) and by NIDDK by interagency agreement Y1-DK-3508-01. N.S. and X.W. contributed equally to this manuscript. NR 34 TC 52 Z9 57 U1 1 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 AUG PY 2011 VL 6 IS 8 BP 1815 EP 1823 DI 10.2215/CJN.11261210 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 805IZ UT WOS:000293721400005 PM 21757640 ER PT J AU Harrison, WW Bearse, MA Schneck, ME Wolff, BE Jewell, NP Barez, S Mick, AB Dolan, BJ Adams, AJ AF Harrison, Wendy W. Bearse, Marcus A., Jr. Schneck, Marilyn E. Wolff, Brian E. Jewell, Nicholas P. Barez, Shirin Mick, Andrew B. Dolan, Bernard J. Adams, Anthony J. TI Prediction, by Retinal Location, of the Onset of Diabetic Edema in Patients with Nonproliferative Diabetic Retinopathy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MACULAR EDEMA; RISK-FACTORS; MULTIFOCAL ELECTRORETINOGRAM; BLOOD-PRESSURE; THICKNESS; TYPE-1; DELAYS; PHOTOCOAGULATION; COMPLICATIONS; DYSFUNCTION AB PURPOSE. To formulate a model to predict the location of the onset of diabetic retinal edema (DE) in adults with diabetic retinopathy (DR), at risk for DE. METHODS. In all, 46 eyes from 23 patients with DR were included. Subjects were followed semiannually until DE developed or the study concluded. The presence or absence of DE within the central 45 at the final visit was the outcome measure, and data from the prior visit were used as baseline. A logistic regression model was formulated to assess the relationship between DE development and: multifocal electroretinogram (mfERG) implicit time (IT) Z-score, mfERG amplitude (Amp) Z-score, sex, diabetes duration, diabetes type, blood glucose, HbA1c, age, systolic (SBP) and diastolic blood pressure, and grade of retinopathy. A total of 35 retinal zones were constructed from the mfERG elements and each was graded for DE. Data from 52 control subjects were used to calculate the maximum IT and minimum Amp Z-scores for each zone. Receiver operating characteristic curves from a fivefold cross-validation were used to determine the model's predictive properties. RESULTS. Edema developed in 5.2% of all retinal zones and in 35% of the eyes. The mfERG Amp, mfERG IT, SBP, and sex were together predictive of edema onset. Combined, these factors produce a model that has 84% sensitivity and 76% specificity. CONCLUSIONS. Together mfERG, SBP, and sex are good predictors of local edema in patients with DR. The model is a useful tool for assessing risk for edema development and a candidate measure to evaluate novel therapeutics directed at DE. (Invest Ophthalmol Vis Sci. 2011;52:6825-6831) DOI:10.1167/iovs.117533 C1 [Harrison, Wendy W.; Bearse, Marcus A., Jr.; Schneck, Marilyn E.; Wolff, Brian E.; Barez, Shirin; Adams, Anthony J.] Univ Calif Berkeley, Sch Optometry, Grp Vis Sci, Berkeley, CA 94720 USA. [Jewell, Nicholas P.] Univ Calif Berkeley, Dept Stat, Div Biostat, Berkeley, CA 94720 USA. [Mick, Andrew B.; Dolan, Bernard J.] San Francisco Vet Adm Med Ctr, Eye Clin, San Francisco, CA USA. RP Harrison, WW (reprint author), Midwestern Univ, Arizona Coll Optometry, 19555 N 59th Ave, Glendale, AZ 85308 USA. EM wharri@midwestern.edu FU National Institutes of Health-National Eye Institute [EY 007043, EY 02271] FX Supported in part by the National Institutes of Health-National Eye Institute Grants EY 007043 and EY 02271 (AJA). NR 49 TC 15 Z9 15 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 AUG PY 2011 VL 52 IS 9 BP 6825 EP 6831 DI 10.1167/iovs.11-7533 PG 7 WC Ophthalmology SC Ophthalmology GA 815SI UT WOS:000294548300060 PM 21743017 ER PT J AU Fick, D Semla, T AF Fick, Donna Semla, Todd TI Improving Medication Use in Gerontological Nursing Now Is the Time for Interdisciplinary Collaboration and Translation SO JOURNAL OF GERONTOLOGICAL NURSING LA English DT Editorial Material ID BEERS CRITERIA; OLDER-ADULTS; INAPPROPRIATE C1 [Fick, Donna] Penn State Univ, Sch Nursing, University Pk, PA 16802 USA. [Semla, Todd] US Dept Vet Affairs, Washington, DC USA. [Semla, Todd] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Semla, Todd] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. RP Fick, D (reprint author), Penn State Univ, Sch Nursing, University Pk, PA 16802 USA. NR 11 TC 2 Z9 4 U1 1 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0098-9134 J9 J GERONTOL NURS JI J. Gerontol. Nurs. PD AUG PY 2011 VL 37 IS 8 BP 3 EP 4 DI 10.3928/00989134-20110603-03 PG 2 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA 812DR UT WOS:000294268500001 PM 21800791 ER PT J AU Dionne, KR Galvin, JM Schittone, SA Clarke, P Tyler, KL AF Dionne, Kalen R. Galvin, John M. Schittone, Stephanie A. Clarke, Penny Tyler, Kenneth L. TI Type I interferon signaling limits reoviral tropism within the brain and prevents lethal systemic infection SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE Reovirus; Virus; Tropism; Interferon; Encephalitis; Brain ID CENTRAL-NERVOUS-SYSTEM; ENCEPHALITIS-VIRUS INFECTION; REGULATORY FACTORS; STIMULATED GENES; TISSUE-INJURY; CELL-DEATH; HOST-CELL; MICE; APOPTOSIS; PROTECTS AB In vivo and ex vivo models of reoviral encephalitis were utilized to delineate the contribution of type I interferon (IFN) to the host's defense against local central nervous system (CNS) viral infection and systemic viral spread. Following intracranial (i.c.) inoculation with either serotype 3 (T3) or serotype 1 (T1) reovirus, increased expression of IFN-alpha, IFN-beta, and myxovirus-resistance protein (Mx1; a prototypical IFN stimulated gene) was observed in mouse brain tissue. Type I IFN receptor deficient mice (IFNAR(-/-)) had accelerated lethality, compared to wildtype (B6wt) controls, following i.c. T1 or T3 challenge. Although viral titers in the brain and eyes of reovirus infected IFNAR(-/-) mice were significantly increased, these mice did not develop neurologic signs or brain injury. In contrast, increased reovirus titers in peripheral tissues (liver, spleen, kidney, heart, and blood) of IFNAR(-/-) mice were associated with severe intestinal and liver injury. These results suggest that reovirus-infected IFNAR(-/-) mice succumb to peripheral disease rather than encephalitis per se. To investigate the potential role of type I IFN in brain tissue, brain slice cultures (BSCs) were prepared from IFNAR(-/-) mice and B6wt controls for ex vivo T3 reovirus infection. Compared to B6wt controls, reoviral replication and virus-induced apoptosis were enhanced in IFNAR(-/-) BSCs indicating that a type I IFN response, initiated by resident CNS cells, mediates innate viral immunity within the brain. T3 reovirus tropism was extended in IFNAR(-/-) brains to include dentate neurons, ependymal cells, and meningeal cells indicating that reovirus tropism within the CNS is dependent upon type I interferon signaling. C1 [Galvin, John M.; Clarke, Penny; Tyler, Kenneth L.] Univ Colorado, Dept Neurol, Aurora, CO 80045 USA. [Tyler, Kenneth L.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. [Tyler, Kenneth L.] Univ Colorado, Dept Med, Aurora, CO 80045 USA. [Schittone, Stephanie A.; Tyler, Kenneth L.] Univ Colorado, Dept Microbiol, Aurora, CO 80045 USA. [Dionne, Kalen R.; Tyler, Kenneth L.] Univ Colorado, Neurosci Program, Aurora, CO 80045 USA. [Dionne, Kalen R.; Tyler, Kenneth L.] Univ Colorado, Med Scientist Training Program, Aurora, CO 80045 USA. RP Tyler, KL (reprint author), Univ Colorado, Dept Neurol, Anschutz Med Campus,Res Complex 2,12700 E 19th Av, Aurora, CO 80045 USA. EM Ken.Tyler@UCDenver.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU VA Merit Grant; institutional MST Program [T32 GM008497]; National Research Service Award [F30 NS071630]; National Research Service [F31 NS06258303]; [RO1NS050138]; [RO1NS051403] FX This work was supported by RO1NS050138 (KLT), RO1NS051403 (KLT), and a VA Merit Grant (KLT). KRD was supported by an institutional MST Program training grant (T32 GM008497) and a National Research Service Award for Individual Predoctoral MD/PhD Fellows (F30 NS071630). SAS was supported by a National Research Service Award for Individual Predoctoral Fellows (F31 NS06258303). The authors extend their gratitude to J. Smith Leser for technical support. We thank Lai Kuan Goh for her critical reading of the manuscript. NR 39 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD AUG PY 2011 VL 17 IS 4 BP 314 EP 326 DI 10.1007/s13365-011-0038-1 PG 13 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 813HA UT WOS:000294356200003 PM 21671121 ER PT J AU Gelman, A Nikolajski, C Schwarz, EB Borrero, S AF Gelman, Amanda Nikolajski, Cara Schwarz, Eleanor Bimla Borrero, Sonya TI Racial Disparities in Awareness of the Human Papillomavirus SO JOURNAL OF WOMENS HEALTH LA English DT Article ID HPV VACCINE; COLLEGE-STUDENTS; AFRICAN-AMERICAN; UNITED-STATES; WOMEN; KNOWLEDGE; ATTITUDES; ACCEPTABILITY; ACCEPTANCE; PARENTS AB Background: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States yet is one of the least recognized among the general public. HPV awareness may be relatively low among minority women. Because HPV awareness is associated with uptake of the HPV vaccine, it is critical to assess HPV awareness in the population and identify any racial/ethnic gaps. Methods: This study used nationally representative data collected by the National Survey of Family Growth between July 2007 and December 2008. A multivariable logistic regression model was used to determine the independent effect of race/ethnicity on HPV awareness while controlling for sociodemographic and clinical confounders in a sample of 4088 women. Stratified multivariable analysis was also conducted to assess the relationship between race/ethnicity and HPV awareness among women in different age groups. Results: After adjusting for confounders, Hispanic and black women overall were significantly less likely to have heard of HPV compared to white women (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.29-0.54 and OR 0.39, 95% CI 0.29-0.54, respectively). Black women aged 15-18 and Hispanic women aged 19-26 had particularly low rates of HPV awareness (OR 0.17, 95% CI 0.07-0.43 and OR 0.18, 95% CI 0.11-0.30, respectively) compared to white women of the same ages. Conclusions: Hispanic and black women have significantly lower levels of HPV awareness than white women. Targeted educational efforts will be important to improve HPV awareness and associated preventive health measures to avoid HPV-related morbidity and mortality. C1 [Gelman, Amanda] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Nikolajski, Cara; Schwarz, Eleanor Bimla; Borrero, Sonya] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Nikolajski, Cara; Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Schwarz, Eleanor Bimla] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Schwarz, Eleanor Bimla] Magee Womens Res Inst, Pittsburgh, PA USA. RP Borrero, S (reprint author), 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM borrerosp@upmc.edu OI Schwarz, Eleanor Bimla/0000-0002-9912-8236 FU University of Pittsburgh's Clinical and Translational Sciences Institute (NIH/NCRR/CTSA) [UL1 RR024153]; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [05 KL2 RR024154-05]; NIH Roadmap for Medical Research; NICHD [K23 HD051585] FX We thank Kwonho Jeong from the University of Pittsburgh's Clinical and Translational Sciences Institute (NIH/NCRR/CTSA grant UL1 RR024153) for his help with statistical analysis. This article was made possible by S.B.'s grant (05 KL2 RR024154-05) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. E. B. S. was supported by NICHD grant K23 HD051585 The content of this publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. NR 41 TC 21 Z9 21 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD AUG PY 2011 VL 20 IS 8 BP 1165 EP 1173 DI 10.1089/jwh.2010.2617 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 805MQ UT WOS:000293731500008 PM 21668381 ER PT J AU Lindsley, CW Bates, BS Menon, UN Jadhav, SB Kane, AS Jones, CK Rodriguez, AL Conn, PJ Olsen, CM Winder, DG Emmitte, KA AF Lindsley, Craig W. Bates, Brittney S. Menon, Usha N. Jadhav, Satyawan B. Kane, Alexander S. Jones, Carrie K. Rodriguez, Alice L. Conn, P. Jeffrey Olsen, Christopher M. Winder, Danny G. Emmitte, Kyle A. TI (3-Cyano-5-fluorophenyl)biaryl Negative Allosteric Modulators of mGlu(5): Discovery of a New Tool Compound with Activity in the OSS Mouse Model of Addiction SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE mGlu(5); negative allosteric modulator; noncompetitive antagonist; addiction ID METABOTROPIC GLUTAMATE-RECEPTOR-5 ANTAGONIST; RECEPTOR SUBTYPE-5 ANTAGONISTS; GLUTAMATE RECEPTORS; GASTROESOPHAGEAL-REFLUX; MGLUR5 ANTAGONISTS; NUCLEUS-ACCUMBENS; SQUIRREL-MONKEYS; COCAINE SEEKING; RECENT PROGRESS; DRUG DISCOVERY AB Glutamate is the major excitatory transmitter in the mammalian central nervous system (CNS), exerting its effects through both ionotropic and metabotropic glutamate am receptors. The metabotropic glutamate receptors (mGlus) belong to family C of the G-protein-coupled receptors (GPCRs). The eight mGlus identified to date are classified into three groups based on their structure, preferred signal transduction mechanisms, and pharmacology (group I: mGlu(1) and mGlus; group II: mGlu(2) and mGlu(3); group III: mGlu(4), mGlu(6), mGlu(7), and mGlu(8)). Noncompetitive antagonists, also known as negative allosteric modulators (NAMs), of mGlus offer potential therapeutic applications in diseases such as pain, anxiety, gastresophageal reflux disease (GERD), Parkinson's disease (PD), fragile X syndrome, and addiction. The development of structure activity relationships (SAR) in a (3-cyano-5-fluorophenyl)biaryl series using our functional cell-based assay is described in this communication. Further characterization of a selected compound, 3-fluoro-(5-(2-methylbenzo[d]thiazol-5-yl)benzonitrile, in additional cell based assays as well as in vitro assays designed to measure its metabolic stability and protein binding indicated its potential utility as an in vivo tool. Subsequent evaluation of the same compound in a pharmacokinetic study using intraperitoneal dosing in mice showed good exposure in both plasma and brain samples. The compound was efficacious in a mouse marble burying model of anxiety, an assay known to be sensitive to mGlus antagonists. A new operant model of addiction termed operant sensation seeking (OSS) was chosen as a second behavioral assay. The compound also proved efficacious in the OSS model and constitutes the first reported example of efficacy with a small molecule mGlu(5) NAM in this novel assay. C1 [Emmitte, Kyle A.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA. [Lindsley, Craig W.; Emmitte, Kyle A.] Vanderbilt Univ, Med Ctr, Dept Chem, Nashville, TN 37232 USA. [Olsen, Christopher M.; Winder, Danny G.] Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Lindsley, Craig W.; Bates, Brittney S.; Menon, Usha N.; Jadhav, Satyawan B.; Kane, Alexander S.; Jones, Carrie K.; Rodriguez, Alice L.; Conn, P. Jeffrey; Emmitte, Kyle A.] US Dept Vet Affairs, Tennesse Valley Healthcare Syst, Nashville, TN 37212 USA. RP Emmitte, KA (reprint author), Vanderbilt Univ, Med Ctr, Dept Pharmacol, Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA. EM kyle.a.emmitte@vanderbilt.edu RI Conn, Peter/D-7848-2012; Winder, Danny/H-4857-2013; Olsen, Christopher/C-3542-2008 OI Olsen, Christopher/0000-0003-2700-0310 FU NIH; NIMH; NIDA [RO1 DA023947-01, K99 DA026994]; Alzheimer's Association; Michael J. Fox Foundation; Seaside Therapeutics [VUMC33842]; JohnsonJohnson; Tennessee Valley Healthcare System (U.S. Department of Veteran's Affairs) FX C.W.L. receives funding from NIH, NIMH, NIDA, the Alzheimer's Association, the Michael J. Fox Foundation, Seaside Therapeutics, and Johnson&Johnson. C.K.J. receives funding from NIMH and Tennessee Valley Healthcare System (U.S. Department of Veteran's Affairs). P.J.C. receives funding from NIH, NIMH, NIDA, the Michael J. Fox Foundation, Seaside Therapeutics, and Johnson&Johnson. C.M.O. receives funding from NIDA. D.G.W. receives funding from NIH, NIDA, NIAAA, and NIMH. K.A.E. receives funding from NIH. The authors thank NIDA (RO1 DA023947-01) and Seaside Therapeutics (VUMC33842) for their support of our programs in the development of noncompetitive antagonist of mGlu5. The authors also thank NIDA (K99 DA026994) for supporting the development and characterization of OSS. NR 71 TC 17 Z9 17 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD AUG PY 2011 VL 2 IS 8 BP 471 EP 482 DI 10.1021/cn100099n PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA 810ST UT WOS:000294148100001 PM 21927650 ER PT J AU Cecere, LM Littman, AJ Slatore, CG Udris, EM Bryson, CL Boyko, EJ Pierson, DJ Au, DH AF Cecere, Laura M. Littman, Alyson J. Slatore, Christopher G. Udris, Edmunds M. Bryson, Chris L. Boyko, Edward J. Pierson, David J. Au, David H. TI Obesity and COPD: Associated Symptoms, Health-related Quality of Life, and Medication Use SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE Obesity; COPD; Health-related quality of life; Symptoms; Inhaled medications; Exacerbations ID OBSTRUCTIVE PULMONARY-DISEASE; PROGNOSTIC VALUE; LUNG HEALTH; SALMETEROL; WEIGHT; RISK; FLUTICASONE; IPRATROPIUM; FORMOTEROL; MORTALITY AB Background: There is little data about the combined effects of COPD and obesity. We compared dyspnea, health-related quality of life (HRQoL), exacerbations, and inhaled medication use among patients who are overweight and obese to those of normal weight with COPD. Methods: We performed secondary data analysis on 364 Veterans with COPD. We categorized subjects by body mass index (BMI). We assessed dyspnea using the Medical Research Council (MRC) dyspnea scale and HRQoL using the St. George's Respiratory Questionnaire. We identified treatment for an exacerbation and inhaled medication use in the past year. We used multiple logistic and linear regression models as appropriate, with adjustment for age, COPD severity, smoking status, and co-morbidities. Results: The majority of our population was male (n = 355, 98%) and either overweight (n = 115, 32%) or obese (n = 138, 38%). Obese and overweight subjects had better lung function (obese: mean FEV(1) 55.4% +/- 19.9% predicted, overweight: mean FEV(1) 50.0% +/- 20.4% predicted) than normal weight subjects (mean FEV(1) 44.2% +/- 19.4% predicted), yet obese subjects reported increased dyspnea [adjusted OR of MRC score >= 2 = 4.91 (95% CI 1.80, 13.39], poorer HRQoL, and were prescribed more inhaled medications than normal weight subjects. There was no difference in any outcome between overweight and normal weight patients. Conclusions: Despite having less severe lung disease, obese patients reported increased dyspnea and poorer HRQoL than normal weight patients. The greater number of inhaled medications prescribed for obese patients may represent overuse. Obese patients with COPD likely need alternative strategies for symptom control in addition to those currently recommended. C1 [Cecere, Laura M.; Udris, Edmunds M.; Bryson, Chris L.; Au, David H.] Dept Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Cecere, Laura M.; Pierson, David J.; Au, David H.] Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98101 USA. [Littman, Alyson J.; Boyko, Edward J.] Dept Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Littman, Alyson J.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. [Slatore, Christopher G.] Dept Vet Affairs Med Ctr, Portland, OR USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Dept Med, Div Pulm & Crit Care Med, Portland, OR 97201 USA. RP Cecere, LM (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM lcecere@u.washington.edu OI Slatore, Christopher/0000-0003-0958-8122; Boyko, Edward/0000-0002-3695-192X FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development [IIR 02-292]; Office of Research and Development Cooperative Studies Program, Department of Veterans Affairs; NIH [2T32HL007287-31]; Veterans Affairs HSRD Fellowship [TPM 61-037]; Veterans Affairs HSR&D Career Development Award; VA Rehabilitation Research and Development Career Development Award [6982]; Giliad Sciences FX This material is based upon work supported by a Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development grant [IIR 02-292]. It is also supported in part by the Office of Research and Development Cooperative Studies Program, Department of Veterans Affairs. Dr. Cecere was previously supported by an NIH institutional training grant [2T32HL007287-31], and is currently supported by a Veterans Affairs HSR&D Fellowship [TPM 61-037]. Dr. Slatore is supported by a Veterans Affairs HSR&D Career Development Award and resources from the Portland VA Medical Center, Portland, OR. Dr. Littman was supported by a VA Rehabilitation Research and Development Career Development Award (#6982). 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. An earlier version of this manuscript was presented in abstract format the American Thoracic Society International Conference, May 2009.; Drs. Au and Bryson are co-investigators on a grant from Giliad Sciences for work which is unrelated to this manuscript. Dr. Boyko has consulted for Ely Lily, Inc. and Seventh Sense Biosystems. Dr. Au sits on the medical editorial board for Nexcura and is a research consultant for Bosch LLC. None of the other authors have any potential conflicts of interest to report. NR 38 TC 28 Z9 29 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1541-2555 J9 COPD JI COPD-J. Chronic Obstr. Pulm. Dis. PD AUG PY 2011 VL 8 IS 4 BP 275 EP 284 DI 10.3109/15412555.2011.586660 PG 10 WC Respiratory System SC Respiratory System GA 811BD UT WOS:000294176000006 PM 21809909 ER PT J AU Thomas, KA Dichter, ME Matejkowski, J AF Thomas, Kristie A. Dichter, Melissa E. Matejkowski, Jason TI Intimate Versus Nonintimate Partner Murder: A Comparison of Offender and Situational Characteristics SO HOMICIDE STUDIES LA English DT Article DE batterers; domestic violence; intimate partner violence; homicide; murder ID FALSE DISCOVERY RATE; DOMESTIC VIOLENCE; HOMICIDE; CRIME; CHICAGO; FEMALE; POLICY; RATES; WOMEN; LEGAL AB To explore whether homicide of intimate partners is distinct from homicide of nonintimates, we compared sociodemographic, legal, family, clinical, and situational characteristics of men who murdered an intimate partner (n = 71) to those of men who murdered a nonintimate (n = 363). Bivariate findings suggest that intimate murder offenders are more socially bonded and conforming regarding employment and relationship patterns and use fatal violence to meet emotional rather than instrumental needs compared to nonintimate offenders. Multivariate findings indicate marital status, history of severe mental illness, and motive are important factors that differentiate men who murder intimates from those who murder nonintimates. Homicide prevention efforts must be tailored to account for factors that differentiate these two offender types. C1 [Thomas, Kristie A.] Simmons Coll, Sch Social Work, Boston, MA 02115 USA. [Dichter, Melissa E.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Matejkowski, Jason] Treatment Res Inst, Sect Law & Eth, Philadelphia, PA USA. RP Thomas, KA (reprint author), Simmons Coll, Sch Social Work, 300 Fenway, Boston, MA 02115 USA. EM kristie.thomas@simmons.edu OI Matejkowski, Jason/0000-0002-0056-4987 NR 48 TC 14 Z9 14 U1 0 U2 21 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1088-7679 J9 HOMICIDE STUD JI Homicide Stud. PD AUG PY 2011 VL 15 IS 3 BP 291 EP 311 DI 10.1177/1088767911417803 PG 21 WC Criminology & Penology SC Criminology & Penology GA 809OU UT WOS:000294067400005 ER PT J AU Kirwan, JR Boonen, A Harrison, MJ Hewlett, SE Wells, GA Singh, JA Furst, DE Dworkin, RH AF Kirwan, John R. Boonen, Annelies Harrison, Mark J. Hewlett, Sarah E. Wells, George A. Singh, Jasvinder A. Furst, Daniel E. Dworkin, Robert H. TI OMERACT 10 Patient Perspective Virtual Campus: Valuing Health; Measuring Outcomes in Rheumatoid Arthritis Fatigue, RA Sleep, Arthroplasty, and Systemic Sclerosis; and Clinical Significance of Changes in Health SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE OUTCOME MEASURES; FATIGUE; ARTHROPLASTY; RHEUMATIC DISEASES ID QUALITY-OF-LIFE; TOTAL KNEE ARTHROPLASTY; INFLAMMATORY ARTHRITIS; POPULATION PREFERENCES; UTILITY MEASURES; TRIALS; QUESTIONNAIRE; EXPERIENCE; VALIDITY; RESPONSIVENESS AB This workshop reviewed progress in a number of areas related to patient perspective outcomes that were not specifically included within other areas of the program. A substantial review of the work of the valuing health outcomes group (the "QALY" working group) with participation and feedback from the plenary audience resulted in guidance to refocus on the use of patient preferences in the elaboration of more robust outcome measures for patient-reported outcomes and life impact measures. Progress and developments in the areas of fatigue and sleep in rheumatoid arthritis, outcome measures in hip and knee arthroplasty clinical trials, and scleroderma were outlined, and the challenge of truly understanding the nature of clinically important improvement was reviewed. (J Rheumatol 2011;38:1728-34; doi:10.3899/jrheum.110393) C1 [Kirwan, John R.] Univ Bristol, Bristol Royal Infirm, Acad Rheumatol Unit, Bristol, Avon, England. [Boonen, Annelies] Maastricht Univ Med Ctr, Maastricht, Netherlands. [Boonen, Annelies] Caphri Res Inst, Maastricht, Netherlands. [Harrison, Mark J.] Univ Manchester, Hlth Methodol Res Grp, Manchester, Lancs, England. [Hewlett, Sarah E.] Univ W England, Bristol Royal Infirm, Acad Rheumatol Unit, Bristol BS16 1QY, Avon, England. [Wells, George A.] Univ Ottawa, Inst Heart, Dept Epidemiol & Community Med, Ottawa, ON, Canada. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama, Birmingham, AL USA. [Furst, Daniel E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY USA. RP Kirwan, JR (reprint author), Univ Bristol, Bristol Royal Infirm, Acad Rheumatol Unit, Bristol, Avon, England. EM john.kirwan@bristol.ac.uk RI Harrison, Mark/E-5788-2012; Agaliotis, Maria/G-5334-2012 OI singh, jasvinder/0000-0003-3485-0006; Kirwan, John/0000-0002-6617-3217 NR 40 TC 9 Z9 9 U1 1 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD AUG PY 2011 VL 38 IS 8 BP 1728 EP 1734 DI 10.3899/jrheum.110393 PG 7 WC Rheumatology SC Rheumatology GA 799VU UT WOS:000293315000034 PM 21807793 ER PT J AU Gossec, L Paternotte, S Bingham, CO Clegg, DO Coste, P Conaghan, PG Davis, AM Giacovelli, G Gunther, KP Hawker, G Hochberg, MC Jordan, JM Katz, JN Kloppenburg, M Lanzarotti, A Lim, K Lohmander, LS Mahomed, NN Maillefert, JF Manno, RL March, LM Mazzuca, SA Pavelka, K Punzi, L Roos, EM Rovati, LC Shi, H Singh, JA Suarez-Almazor, ME Tajana-Messi, E Dougados, M AF Gossec, Laure Paternotte, Simon Bingham, Clifton O., III Clegg, Daniel O. Coste, Philippe Conaghan, Philip G. Davis, Aileen M. Giacovelli, Giampaolo Gunther, Klaus-Peter Hawker, Gillian Hochberg, Marc C. Jordan, Joanne M. Katz, Jeffrey N. Kloppenburg, Margreet Lanzarotti, Arturo Lim, Keith Lohmander, L. Stefan Mahomed, Nizar N. Maillefert, Jean Francis Manno, Rebecca L. March, Lyn M. Mazzuca, Steven A. Pavelka, Karel Punzi, Leonardo Roos, Ewa M. Rovati, Lucio C. Shi, Helen Singh, Jasvinder A. Suarez-Almazor, Maria E. Tajana-Messi, Eleonora Dougados, Maxime CA OARSI-OMERACT Task Force Total Art TI OARSI/OMERACT Initiative to Define States of Severity and Indication for Joint Replacement in Hip and Knee Osteoarthritis. An OMERACT 10 Special Interest Group SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE OSTEOARTHRITIS; SEVERITY; PAIN; FUNCTION; STRUCTURE OUTCOME MEASURE ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; RADIOGRAPHIC FEATURES; GLUCOSAMINE SULFATE; PHYSICAL-FUNCTION; PROGRESSION; PAIN; ASSOCIATION; 3-YEAR; 2-YEAR AB Objective. To define pain and physical function cutpoints that would, coupled with structural severity, define a surrogate measure of "need for joint replacement surgery," for use as an outcome measure for potential structure-modifying interventions for osteoarthritis (OA). Methods. New scores were developed for pain and physical function in knee and hip OA. A cross-sectional international study in 1909 patients was conducted to define data-driven cutpoints corresponding to the orthopedic surgeons' indication for joint replacement. A post hoc analysis of 8 randomized clinical trials (1379 patients) evaluated the prevalence and validity of cutpoints, among patients with symptomatic hip/knee OA. Results. In the international cross-sectional study, there was substantial overlap in symptom levels between patients with and patients without indication for joint replacement; indeed, it was not possible to determine cutpoints for pain and function defining this indication. The post hoc analysis of trial data showed that the prevalence of cases that combined radiological progression, high level of pain, and high degree of function impairment was low (2%-12%). The most discriminatory cutpoint to define an indication for joint replacement was found to be [pain (0-100) + physical function (0-100) > 80]. Conclusion. These results do not support a specific level of pain or function that defines an indication for joint replacement. However, a tentative cutpoint for pain and physical function levels is proposed for further evaluation. Potentially, this symptom level, coupled with radiographic progression, could be used to define "nonresponders" to disease-modifying drugs in OA clinical trials. (J Rheumatol 2011;38:1765-9; doi:10.3899/jrheum.110403) C1 [Gossec, Laure; Paternotte, Simon; Dougados, Maxime] Paris Descartes Univ, Fac Med, Paris, France. [Gossec, Laure; Paternotte, Simon; Dougados, Maxime] Cochin Hosp, AP HP, Rheumatol Dept B, Paris, France. [Bingham, Clifton O., III; Manno, Rebecca L.] Johns Hopkins Univ, Div Rheumatol, Baltimore, MD USA. [Bingham, Clifton O., III] Johns Hopkins Univ, Div Clin Immunol & Allergy, Baltimore, MD USA. [Clegg, Daniel O.] Univ Utah, Sch Med, Dept Internal Med, Div Rheumatol, Salt Lake City, UT USA. [Coste, Philippe] Expansci Labs, Courbevoie, France. [Conaghan, Philip G.] Univ Leeds, Sect Musculoskeletal Dis, Leeds, W Yorkshire, England. [Conaghan, Philip G.] NIHR Leeds Musculoskeletal Biomed Res Unit, Leeds, W Yorkshire, England. [Davis, Aileen M.] Univ Toronto, Div Hlth Care & Outcomes Res, Toronto, ON, Canada. [Davis, Aileen M.] Univ Toronto, Toronto Western Res Inst, Arthrit & Community Res & Evaluat Unit, Toronto, ON, Canada. [Davis, Aileen M.] Univ Toronto, Dept Rehabil Sci, Toronto, ON, Canada. [Giacovelli, Giampaolo] Rottapharm Madaus, Dept Clin Pharmacol, Dept Biostat, Monza, Italy. [Gunther, Klaus-Peter] Univ Dresden, Dept Orthopaed Surg, Dresden, Germany. [Hawker, Gillian] Univ Toronto, Womens Coll Hosp, Div Rheumatol, Dept Med, Toronto, ON M5S 1A1, Canada. [Hawker, Gillian] Univ Toronto, Fac Med, Dept Hlth Policy Management & Evaluat, Clin Epidemiol & Hlth Care Res Program, Toronto, ON M5S 1A1, Canada. [Hochberg, Marc C.] Univ Maryland, Sch Med, Dept Med, Div Clin Immunol & Rheumatol, Baltimore, MD 21201 USA. [Hochberg, Marc C.] Univ Maryland, Sch Med, Div Gerontol, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Jordan, Joanne M.] Univ N Carolina, Sch Med, Thurston Arthrit Res Ctr, Div Rheumatol Allergy & Immunol,Dept Med, Chapel Hill, NC USA. [Katz, Jeffrey N.] Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Sch Med, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Dept Orthoped Surg, Sch Med, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kloppenburg, Margreet] Leiden Univ, Med Ctr, Dept Clin Epidemiol, Dept Rheumatol, Leiden, Netherlands. [Lanzarotti, Arturo; Tajana-Messi, Eleonora] IBSA Inst Biochim SA, R&D Dept, Pambio Noranco, Switzerland. [Lim, Keith] St Vincents Hosp, Dept Rheumatol, Melbourne, Vic, Australia. [Lim, Keith] Western Hosp, Melbourne, Vic, Australia. [Lohmander, L. Stefan] Lund Univ, Dept Orthopaed, Lund, Sweden. [Mahomed, Nizar N.] Univ Toronto, Toronto Western Hosp, Div Orthopaed Surg, Toronto, ON M5T 2S8, Canada. [Maillefert, Jean Francis] Dijon Univ Hosp, Dept Rheumatol, Dijon, France. [Maillefert, Jean Francis] Univ Burgundy, Dijon, France. [Maillefert, Jean Francis] INSERM, U887, Dijon, France. [March, Lyn M.] Univ Sydney, Royal N Shore Hosp, Inst Bone & Joint Res, St Leonards, NSW 2065, Australia. [Mazzuca, Steven A.] Indiana Univ Sch Med, Indianapolis, IN USA. [Pavelka, Karel] Charles Univ Prague, Inst Rheumatol, Prague, Czech Republic. [Punzi, Leonardo] Univ Padua, Dept Clin & Expt Med, Rheumatol Unit, Padua, Italy. [Roos, Ewa M.] Univ So Denmark, Inst Sports & Clin Biomech, Odense, Denmark. [Shi, Helen] VA Cooperat Studies Program Coordinating Ctr, Hines, IL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama, Birmingham, AL USA. [Suarez-Almazor, Maria E.] Univ Texas MD Anderson Canc Ctr, Rheumatol Sect, Houston, TX 77030 USA. RP Dougados, M (reprint author), Paris Descartes Univ, Fac Med, Paris, France. EM maxime.dougados@cch.aphp.fr RI Roos, Ewa/A-5416-2012; Lohmander, Stefan/I-8326-2012; DOUGADOS, MAXIME/P-5287-2016; Pavelka, Karel/E-6578-2017 OI Roos, Ewa/0000-0001-5425-2199; Pavelka, Karel/0000-0003-1952-8422; PUNZI, LEONARDO/0000-0002-8853-516X; Lohmander, Stefan/0000-0002-5424-9448; singh, jasvinder/0000-0003-3485-0006 FU OARSI; OMERACT; pharmaceutical companies Pfizer; Expansciences; Novartis; Negma Lerads; Rottapharm-Madaus; Fidia; Pierre Fabre Sante Laboratories; KOSTAR; Swedish Research Council; National Institutes of Health (NIH) [1 KL2 RR024151-01, T32 AR48522-06]; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Agency for Healthcare Research; Houston Center for Education and Research on Therapeutics (CERT); Allergan; Takeda; Savient; Wyeth and Amgen FX Supported by unrestricted grants from OARSI and OMERACT and pharmaceutical companies Pfizer, Expansciences, Novartis, Negma Lerads, Rottapharm-Madaus, Fidia, and Pierre Fabre Sante Laboratories. Procter and Gamble Pharmaceuticals provided unrestricted access to placebo data from the KOSTAR study and an unrestricted grant to COB. LSL was supported by the Swedish Research Council; JAS was supported by the National Institutes of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research). MSA holds a K24 award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and is partially supported by the Agency for Healthcare Research and Quality through finding of the Houston Center for Education and Research on Therapeutics (CERT). RLM is supported by NIH Training Grant T32 AR48522-06. P. Caste is an employee of Expanscience; A. Lanzaroni and E. Tajana-Messi are employees of IBSA; L.C. Rovati and G. Giacovelli are employees of Rottapharm-Madaus; COB served as a consultant and investigator for Procter and Gamble Pharmaceuticals, Novartis, and Merck and received an unrestricted grant from P&G Pharmaceuticals; LM has received a speaker honorarium and travel grant from Servier. JAS has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth and Amgen; and consultant fees from Savient and URL pharmaceuticals. NR 24 TC 33 Z9 33 U1 1 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD AUG PY 2011 VL 38 IS 8 BP 1765 EP 1769 DI 10.3899/jrheum.110403 PG 5 WC Rheumatology SC Rheumatology GA 799VU UT WOS:000293315000040 PM 21807799 ER PT J AU Wen, HY Schumacher, HR Pullman-Mooar, SW Einhorn, E AF Wen, Hongyan Schumacher, H. Ralph Pullman-Mooar, Sally W. Einhorn, Eugene TI Unusual Draining Nodules in a Patient with Rheumatoid Nodulosis and Hepatitis C Virus Infection SO JOURNAL OF RHEUMATOLOGY LA English DT Letter ID ARTHRITIS; CLASSIFICATION; AUTOANTIBODIES; ASSOCIATION; ANTIBODIES; CRITERIA C1 [Wen, Hongyan; Schumacher, H. Ralph; Pullman-Mooar, Sally W.] Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Einhorn, Eugene] Philadelphia Vet Affairs Med Ctr, Dept Pathol, Philadelphia, PA USA. [Wen, Hongyan] Shanxi Med Univ, Hosp 2, Taiyuan, Shanxi Province, Peoples R China. RP Schumacher, HR (reprint author), Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. EM schumacr@mail.med.upenn.edu NR 15 TC 0 Z9 0 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD AUG PY 2011 VL 38 IS 8 BP 1806 EP 1808 DI 10.3899/jrheum.110244 PG 3 WC Rheumatology SC Rheumatology GA 799VU UT WOS:000293315000046 PM 21807805 ER PT J AU Hunter, DJ Guermazi, A Lo, GH Grainger, AJ Conaghan, PG Boudreau, RM Roemer, FW AF Hunter, D. J. Guermazi, A. Lo, G. H. Grainger, A. J. Conaghan, P. G. Boudreau, R. M. Roemer, F. W. TI Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score) SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE MRI; Knee osteoarthritis; Semi-quantitative score; Reliability ID ANTERIOR CRUCIATE LIGAMENT; BONE-MARROW LESIONS; ARTICULAR-CARTILAGE; DIAGNOSTIC PERFORMANCE; PROTON-DENSITY; TRUE-FISP; 3.0 T; CONVENTIONAL MR; MENISCAL TEARS; RESONANCE AB Objective: In an effort to evolve semi-quantitative scoring methods based upon limitations identified in existing tools, integrating expert readers' experience with all available scoring tools and the published data comparing the different scoring systems, we iteratively developed the magnetic resonance imaging (MRI) Osteoarthritis Knee Score (MOAKS). The purpose of this report is to describe the instrument and its reliability. Methods: The MOAKS instrument refines the scoring of bone marrow lesions (BMLs) (providing regional delineation and scoring across regions), cartilage (sub-regional assessment), and refines the elements of meniscal morphology (adding meniscal hypertrophy, partial maceration and progressive partial maceration) scoring. After a training and calibration session two expert readers read MRIs of 20 knees separately. In addition, one reader re-read the same 20 MRIs 4 weeks later presented in random order to assess intra-rater reliability. The analyses presented here are for both intra- and inter-rater reliability (calculated using the linear weighted kappa and overall percent agreement). Results: With the exception of inter-rater reliability for tibial cartilage area (kappa = 0.36) and tibial osteophytes (kappa = 0.49); and intra-rater reliability for tibial BML number of lesions (kappa = 0.54), Hoffa-synovitis (kappa = 0.42) all measures of reliability using kappa statistics were very good (0.61-0.8) or reached near-perfect agreement (0.81-1.0). Only intra-rater reliability for Hoffa-synovitis, and inter-rater reliability for tibial and patellar osteophytes showed overall percent agreement <75%. Conclusion: MOAKS scoring shows very good to excellent reliability for the large majority of features assessed. Further iterative development and research will include assessment of its validation and responsiveness. (C) 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Hunter, D. J.] Univ Sydney, Dept Rheumatol, No Clin Sch, Royal N Shore Hosp, Sydney, NSW 2065, Australia. [Guermazi, A.; Roemer, F. W.] Boston Univ, Sch Med, Quantitat Imaging Ctr, Dept Radiol, Boston, MA 02118 USA. [Lo, G. H.] Michael E DeBakey Vet Adm Med Ctr, Med Care Line Res Care Line & Houston Hlth Serv R, Ctr Excellence, Houston, TX USA. [Lo, G. H.] Baylor Coll Med, Dept Med, Sect Immunol Allergy & Rheumatol, Houston, TX 77030 USA. [Grainger, A. J.] Leeds Teaching Hosp, Dept Radiol, Leeds, W Yorkshire, England. [Grainger, A. J.; Conaghan, P. G.] NIHR Leeds Musculoskeletal Biomed Res Unit, Leeds, W Yorkshire, England. [Conaghan, P. G.] Univ Leeds, Sect Musculoskeletal Dis, Leeds, W Yorkshire, England. [Boudreau, R. M.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Roemer, F. W.] Klinikum Augsburg, Dept Radiol, Augsburg, Germany. RP Hunter, DJ (reprint author), Univ Sydney, Dept Rheumatol, No Clin Sch, Royal N Shore Hosp, Sydney, NSW 2065, Australia. EM David.Hunter@sydney.edu.au RI Hunter, David/A-4622-2010 OI Hunter, David/0000-0003-3197-752X; Boudreau, Robert/0000-0003-0162-5187 FU AstraZeneca; DonJoy; Lilly; Merck; NIH; Pfizer; Stryker; Wyeth; GE Healthcare; Australian Research Council FX David Hunter receives research or institutional support from AstraZeneca, DonJoy, Lilly, Merck, NIH, Pfizer, Stryker and Wyeth. Ali Guermazi receives research or institutional support from NIH and GE Healthcare. He is consultant to MerckSerono, Stryker, Genzyme and Novartis. He is President of BICL (Boston Imaging Core Lab), LLC, a company providing radiologic image assessment services.; Dr Hunter is supported by an Australian Research Council Future Fellowship. We would like to acknowledge the support of Dr Daniel Gale who contributed to BLOKS and the initial development of MOAKS. NR 53 TC 127 Z9 129 U1 0 U2 8 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD AUG PY 2011 VL 19 IS 8 BP 990 EP 1002 DI 10.1016/j.joca.2011.05.004 PG 13 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 811UA UT WOS:000294240400009 PM 21645627 ER PT J AU Pangarkar, S Lee, PC AF Pangarkar, Sanjog Lee, Paul C. TI Conservative Treatment for Neck Pain: Medications, Physical Therapy, and Exercise SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA LA English DT Article DE Neck pain; Medications; Exercise; Physical therapy; Modalities ID RANDOMIZED-CONTROLLED-TRIAL; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BOTULINUM-TOXIN-A; LOW-BACK-PAIN; ELECTRICAL NERVE-STIMULATION; SKELETAL-MUSCLE RELAXANT; TRIGGER-POINT INJECTION; ACUTE LIVER-FAILURE; DOUBLE-BLIND; NEUROPATHIC PAIN AB This article offers conservative treatment strategies for patients suffering from musculoskeletal causes of neck pain. Basic pharmacology is reviewed, including that of opioids, nonsteroidal anti-inflammatory drugs, adjuvants, and topical analgesics. Moreover, indications for therapeutic exercise, manual therapy, and modalities are reviewed, along with any supporting literature. Treatment considerations with each category of medication and physical therapy are discussed. This article is meant to serve as a resource for physicians to tailor conservative treatment options to their individual patients. C1 [Pangarkar, Sanjog; Lee, Paul C.] VA Greater Los Angeles, Dept Phys Med & Rehabil, Los Angeles, CA 90073 USA. [Pangarkar, Sanjog] Univ Calif Los Angeles, David Geffen Sch Med, Vet Hlth Serv Greater Los Angeles, Inpatient Pain Serv, Los Angeles, CA 90073 USA. [Lee, Paul C.] UCLA VA Greater Los Angeles Multicampus Phys Med, Los Angeles, CA 90073 USA. RP Lee, PC (reprint author), VA Greater Los Angeles, Dept Phys Med & Rehabil, Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Lee.Paul.C@gmail.com NR 107 TC 7 Z9 7 U1 1 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1047-9651 EI 1558-1381 J9 PHYS MED REH CLIN N JI Phys. Med. Rehabil. Clin. N. Am. PD AUG PY 2011 VL 22 IS 3 BP 503 EP + DI 10.1016/j.pmr.2011.04.001 PG 19 WC Rehabilitation SC Rehabilitation GA 813NL UT WOS:000294374100012 PM 21824590 ER PT J AU Schneiderman, JS Hazlett, EA Chu, KW Zhang, J Goodman, CR Newmark, RE Torosjan, Y Canfield, EL Entis, J Mitropoulou, V Tang, CY Friedman, J Buchsbaum, MS AF Schneiderman, Jason S. Hazlett, Erin A. Chu, King-Wai Zhang, Jane Goodman, Chelain R. Newmark, Randall E. Torosjan, Yuliya Canfield, Emily L. Entis, Jonathan Mitropoulou, Vivian Tang, Cheuk Y. Friedman, Joseph Buchsbaum, Monte S. TI Brodmann area analysis of white matter anisotropy and age in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; White matter; Diffusion Tensor Imaging; Anisotropy; Brodmann areas; Age ID DIFFUSION TENSOR ANISOTROPY; AUDITORY HALLUCINATIONS; METABOLIC-RATE; TRACTOGRAPHY; ABNORMALITIES; DISORDER; CONNECTIONS; SYMPTOMS; DEFICITS; PET AB Diffusion tensor and structural MRI images were acquired on ninety-six patients with schizophrenia (69 men and 27 women) between the ages of 18 and 79 (mean = 39.83, SD = 15.16 DSM-IV diagnosis of schizophrenia according to the Comprehensive Assessment of Symptoms and History). The patients reported a mean age of onset of 23 years (range = 13-38, SD = 6). Patients were divided into an acute subgroup (duration <= 3 years, n = 25), and a chronic subgroup (duration >3 years, n = 64). Ninety-three mentally normal comparison subjects were recruited; 55 men and 38 women between the ages of 18 and 82 (mean = 35.77, SD = 18.12). The MRI images were segmented by Brodmann area, and the fractional anisotropy (FA) for the white matter within each Brodmann area was calculated. The FA in white matter was decreased in patients with schizophrenia broadly across the entire brain, but to a greater extent in white matter underneath frontal, temporal and cingulate cortical areas. Both normals and patients with schizophrenia showed a decrease in anisotropy with age but patients with schizophrenia showed a significantly greater rate of decrease in FA in Brodmann area 10 bilaterally, 11 in the left hemisphere and 34 in the right hemisphere. When the effect of age was removed, patients ill more than three years showed lower anisotropy in frontal motor and cingulate white matter in comparison to acute patients ill three years or less, consistent with an ongoing progression of the illness. (C) 2011 Elsevier B.V. All rights reserved. C1 [Schneiderman, Jason S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat,Psychiat Neuroimaging Lab, Boston, MA 02215 USA. [Hazlett, Erin A.; Chu, King-Wai; Zhang, Jane; Goodman, Chelain R.; Newmark, Randall E.; Torosjan, Yuliya; Canfield, Emily L.; Entis, Jonathan; Mitropoulou, Vivian; Friedman, Joseph] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Tang, Cheuk Y.] Mt Sinai Sch Med, Dept Radiol, New York, NY 10029 USA. [Hazlett, Erin A.] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Hazlett, Erin A.] MIRECC, Bronx, NY 10468 USA. [Buchsbaum, Monte S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Buchsbaum, Monte S.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92093 USA. RP Schneiderman, JS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat,Psychiat Neuroimaging Lab, 1249 Boylston St, Boston, MA 02215 USA. EM jason@bwh.harvard.edu RI Schneiderman, Jason/E-1528-2013 OI Schneiderman, Jason/0000-0002-9313-0415 FU NIMH [P50MH06639, T32MH016259] FX Funding was provided by NIMH Grant P50MH06639 and T32MH016259; the NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 43 TC 17 Z9 17 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2011 VL 130 IS 1-3 BP 57 EP 67 DI 10.1016/j.schres.2011.04.027 PG 11 WC Psychiatry SC Psychiatry GA 811SZ UT WOS:000294237700009 PM 21600737 ER PT J AU Katsel, P Tan, WL Abazyan, B Davis, KL Ross, C Pletnikov, MV Haroutunian, V AF Katsel, Pavel Tan, Weilun Abazyan, Bagrat Davis, Kenneth L. Ross, Christopher Pletnikov, Mikhail V. Haroutunian, Vahram TI Expression of mutant human DISC1 in mice supports abnormalities in differentiation of oligodendrocytes SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Disrupted-in schizophrenia 1; Gene expression; Oligodendrocyte; Oligodendrogenesis; Myelin; Neuregulin ID MESSENGER-RNA EXPRESSION; MULTIPLE BRAIN-REGIONS; CENTRAL-NERVOUS-SYSTEM; PDGF-ALPHA-RECEPTOR; GENE-EXPRESSION; PREFRONTAL CORTEX; BIPOLAR DISORDER; IN-VIVO; BEHAVIORAL PHENOTYPES; CHROMOSOME 1Q42 AB Abnormalities in oligodendrocyte (OLG) differentiation and OLG gene expression deficit have been described in schizophrenia (SZ). Recent studies revealed a critical requirement for Disrupted-in-Schizophrenia 1 (DISCI) in neural development. Transgenic mice with forebrain restricted expression of mutant human DISC1 (Delta hDISC1) are characterized by neuroanatomical and behavioral abnormalities reminiscent of some features of SZ. We sought to determine whether the expression of Delta hDISC1 may influence the development of OLGs in this mouse model. OLG- and cell cycle-associated gene and protein expression were characterized in the forebrain of Delta hDISC1 mice during different stages of neurodevelopment (E15 and P1 days) and in adulthood. The results suggest that the expression of Delta hDISC1 exerts a significant influence on oligodendrocyte differentiation and function, evidenced by premature OLG differentiation and increased proliferation of their progenitors. Additional findings showed that neuregulin 1 and its receptors may be contributing factors to the observed upregulation of OLG genes. Thus, OLG function may be perturbed by mutant hDISC1 in a model system that provides new avenues for studying aspects of the pathogenesis of SZ. (C) 2011 Elsevier B.V. All rights reserved. C1 [Katsel, Pavel; Tan, Weilun; Davis, Kenneth L.; Haroutunian, Vahram] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Haroutunian, Vahram] James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. [Abazyan, Bagrat; Ross, Christopher; Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. [Abazyan, Bagrat; Ross, Christopher; Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Abazyan, Bagrat; Ross, Christopher; Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Parhobiol, Baltimore, MD USA. RP Katsel, P (reprint author), Bronx VA Med Ctr, Room 4F-20,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM pavel.katsel@mssm.edu FU NIH [MH064673, MH66392]; NIMH; Conte VA Merit award; Mental Illness Research and Education Clinical Center (MIRECC) [VISN3] FX This study was supported by NIH Grants MH064673, MH66392, NIMH ARRA grant, Conte VA Merit award and by the VISN3 Mental Illness Research and Education Clinical Center (MIRECC). NR 77 TC 18 Z9 19 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2011 VL 130 IS 1-3 BP 238 EP 249 DI 10.1016/j.schres.2011.04.021 PG 12 WC Psychiatry SC Psychiatry GA 811SZ UT WOS:000294237700035 PM 21605958 ER PT J AU Fukatsu, K Kudsk, KA AF Fukatsu, Kazuhiko Kudsk, Kenneth A. TI Nutrition and Gut Immunity SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article DE Phospholipase A2; Gut-associated lymphoid tissue; Immunoglobulin A; Glutamine; Mucosal immunity; Enteral nutrition; Parenteral nutrition ID TOTAL PARENTERAL-NUTRITION; UPPER RESPIRATORY-TRACT; IMMUNOGLOBULIN-A LEVELS; LYMPHOTOXIN-BETA-RECEPTOR; KAPPA-B ACTIVATION; ADHESION MOLECULE-1 EXPRESSION; MAJOR ABDOMINAL-TRAUMA; NECROSIS-FACTOR-ALPHA; CHAIN FATTY-ACIDS; LYMPHOID-TISSUE AB The human intestine contains huge amounts of nonpathologic bacteria surviving in an environment that is beneficial to both the host and the bacterial populations. When short pauses in oral intake occur with minimal alterations in the mucosa-microbial interface, critical illness, with its attendant acidosis, prolonged gastrointestinal tract starvation, exogenous antibiotics, and breakdown in mucosal defenses, renders the host vulnerable to bacterial challenge and also threatens the survival of the bacteria. This review examines the altered innate and adaptive immunologic host defenses that occur as a result of altered oral or enteral intake and/or injury. C1 [Kudsk, Kenneth A.] Univ Wisconsin Sch Med & Publ Hlth, Dept Surg, Madison, WI 53792 USA. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. [Fukatsu, Kazuhiko] Tokyo Univ Hosp, Surg Ctr, Dept Surg, Bunkyo Ku, Tokyo 1138655, Japan. RP Kudsk, KA (reprint author), Univ Wisconsin Sch Med & Publ Hlth, Dept Surg, 600 Highland Ave,G5-341, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu FU National Institute of Health (NIH) [R01 GM53439]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Service FX This research is supported by National Institute of Health (NIH) Grant R01 GM53439. This material is also based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Service. The contents of the article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 77 TC 26 Z9 29 U1 0 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD AUG PY 2011 VL 91 IS 4 BP 755 EP + DI 10.1016/j.suc.2011.04.007 PG 17 WC Surgery SC Surgery GA 811FC UT WOS:000294188400005 PM 21787966 ER PT J AU McCutcheon, SR AF McCutcheon, Stephen R. TI The Internship Crisis: An Uncommon Urgency To Build a Common Solution SO TRAINING AND EDUCATION IN PROFESSIONAL PSYCHOLOGY LA English DT Editorial Material DE internship imbalance; predoctoral internship; Common Pool Resource; CCTC ID PROFESSIONAL PSYCHOLOGY AB The internship imbalance is a problem of grave individual and professional concern. As the imbalance continues and deepens, many concerted efforts have been directed toward mitigating the imbalance by addressing factors associated with increased demand and insufficient supply of internship positions. These efforts have required the collaboration of groups and organizations that in the past pursued different aims and agendas. Hatcher (this issue, pp. 126-140) moves these efforts forward greatly, by conceptualizing the internship imbalance as a specific example of a scarce resource shared by a large community (a Common Pool Resource) and by providing a framework for development of a governance structure to manage this common resource. This commentary expands on Hatcher (this issue) by highlighting important structural and attitudinal issues underlying the imbalance problem that are evoked by attempts to address the imbalance, and which must be considered when formulating a comprehensive and integrated solution, particularly one that includes an additional governance structure dependent on interorganizational collaboration. C1 [McCutcheon, Stephen R.] Puget Sound Healthcare Syst, Vet Affairs, Seattle, WA USA. RP McCutcheon, SR (reprint author), VA Puget Sound, Mental Hlth 116 POC,1660 S Columbian Way, Seattle, WA 98108 USA. EM stephen.mccutcheon@va.gov NR 21 TC 12 Z9 12 U1 1 U2 1 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1931-3918 J9 TRAIN EDUC PROF PSYC JI Train. Educ. Prof. Psychol. PD AUG PY 2011 VL 5 IS 3 BP 144 EP 148 DI 10.1037/a0024896 PG 5 WC Psychology, Educational SC Psychology GA 810CF UT WOS:000294102300004 ER PT J AU Chen, D Restrepo, MI Fine, MJ Pugh, MJV Anzueto, A Metersky, ML Nakashima, B Good, C Mortensen, EM AF Chen, Dennis Restrepo, Marcos I. Fine, Michael J. Pugh, Mary Jo V. Anzueto, Antonio Metersky, Mark L. Nakashima, Brandy Good, Chester Mortensen, Eric M. TI Observational Study of Inhaled Corticosteroids on Outcomes for COPD Patients with Pneumonia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE inhaled corticosteroids; pneumonia; chronic obstructive pulmonary disease; mortality ID OBSTRUCTIVE PULMONARY-DISEASE; COMMUNITY-ACQUIRED PNEUMONIA; SALMETEROL/FLUTICASONE PROPIONATE; FLUTICASONE PROPIONATE; RISK-FACTORS; ADMINISTRATIVE DATA; COMORBIDITY INDEX; SALMETEROL; MORTALITY; EXACERBATIONS AB Rationale: Treatment with inhaled corticosteroids (ICS) for those with chronic obstructive pulmonary disease (COPD) has been shown to be associated with an increased incidence of pneumonia. However, it is unclear if this is associated with increased mortality. Objectives: The aim of this study was to examine the effects of prior use of ICS on clinical outcomes for patients with COPD hospitalized with pneumonia. Methods: We conducted a retrospective cohort study using the national administrative databases of the Department of Veterans Affairs. Eligible patients had a preexisting diagnosis of COPD, had a discharge diagnosis of pneumonia, and received treatment with one or more appropriate pulmonary medications before hospitalization. Outcomes included mortality, use of invasive mechanical ventilation, and vasopressor use. Measurements and Main Results: There were 15,768 patients (8,271 with use of ICS and 7,497 with no use of ICS) with COPD who were hospitalized for pneumonia. There was also a significant difference for 90-day mortality (ICS 17.3% vs. no ICS 22.8%; P < 0.001). Multilevel regression analyses demonstrated that prior receipt of ICS was associated with decreased mortality at 30 days (odds ratio [OR] 0.80; 95% confidence interval [CI], 0.72-0.89) and 90 days (OR 0.78; 95% CI, 0.72-0.85), and decreased use of mechanical ventilation (OR 0.83; 95% CI, 0.72-0.94). There was no significant association between receipt of ICS and vasopressor use (OR 0.88; 95% CI, 0.74-1.04). Conclusions: For patients with COPD, prior use of ICS is independently associated with decreased risk of short-term mortality and use of mechanical ventilation after hospitalization for pneumonia. C1 [Chen, Dennis; Restrepo, Marcos I.; Pugh, Mary Jo V.; Anzueto, Antonio; Nakashima, Brandy; Mortensen, Eric M.] VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Mortensen, Eric M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hosp Med, San Antonio, TX 78229 USA. [Restrepo, Marcos I.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Biostat, San Antonio, TX 78229 USA. [Metersky, Mark L.] Univ Connecticut, Sch Med, Div Pulm & Crit Care Med, Farmington, CT USA. [Fine, Michael J.; Good, Chester] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Fine, Michael J.; Good, Chester] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. RP Mortensen, EM (reprint author), STVHCS UTHSCSA, VERDICT Res Program 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM mortensene@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 OI Pugh, Mary Jo/0000-0003-4196-7763; Mortensen, Eric/0000-0002-3880-5563 FU National Institute of Nursing Research [R01NR010828]; Department of Veteran Affairs Veterans Integrated Service Network [17]; National Health Institute [KL2 RR025766]; Veterans Health Administration [MRP-05-145] FX Supported by Grant Number R01NR010828 from the National Institute of Nursing Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Nursing Research or the National Institutes of Health. This material is the result of work supported with resources and the use of facilities at the South Texas Veterans Health Care System. Dr. Restrepo is supported by a Department of Veteran Affairs Veterans Integrated Service Network 17 new faculty grant and National Health Institute Grant KL2 RR025766. Dr. Copeland is supported by Veterans Health Administration Grant MRP-05-145. The funding agencies had no role in conducting the study, or role in the preparation, review, or approval of the manuscript. NR 36 TC 44 Z9 44 U1 0 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 1 PY 2011 VL 184 IS 3 BP 312 EP 316 DI 10.1164/rccm.201012-2070OC PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 808EE UT WOS:000293958800009 PM 21512168 ER PT J AU Singh, JA Kwoh, CK Boudreau, RM Lee, GC Ibrahim, SA AF Singh, Jasvinder A. Kwoh, C. Kent Boudreau, Robert M. Lee, Gwo-Chin Ibrahim, Said A. TI Hospital Volume and Surgical Outcomes After Elective Hip/Knee Arthroplasty A Risk-Adjusted Analysis of a Large Regional Database SO ARTHRITIS AND RHEUMATISM LA English DT Article ID TOTAL KNEE ARTHROPLASTY; MYOCARDIAL-INFARCTION MORTALITY; SURGEON PROCEDURE VOLUME; TOTAL HIP-REPLACEMENT; REVISION TOTAL HIP; UNITED-STATES; PROVIDER VOLUME; RIGHT TOOL; APR-DRGS; ASSOCIATION AB Objective. To examine the relationship between hospital procedure volume and surgical outcomes following elective primary total hip arthroplasty/total knee arthroplasty (THA/TKA). Methods. Using the Pennsylvania Health Care Cost Containment Council database, we identified all patients who underwent elective primary THA/TKA in Pennsylvania. Hospitals were categorized according to the annual volume of THA/TKA procedures, as follows: <= 25, 26-100, 101-200, and >200. The 30-day complication rate and 30-day and 1-year mortality rates were assessed by logistic regression models, adjusted for age, sex, race, insurance type, hospital region, 3M All Patient Refined Diagnosis Related Group risk of mortality score, hospital teaching status, and bed count. Results. In the THA and TKA cohorts, the mean age of the patients was 69 years, and 42.8% and 35%, respectively, were men. Compared with patients whose surgeries were performed at very-high-volume hospitals (> 200 procedures/year), patients who underwent elective primary THA procedures at hospitals with a very low volume (<= 25 procedures/year), a low volume (26100 procedures/year), or a high volume (101-200 procedures/year) had higher multivariable-adjusted odds ratios (ORs) for venous thromboembolism (OR 2.0, 95% confidence interval [95% CI] 0.2-16.0), OR 3.4 [95% CI 1.4-8.0], and OR 1.1 [95% CI 0.3-3.7], respectively) and 1-year mortality (OR 2.1 [95% CI 1.2-3.6], OR 2.0 [95% CI 1.4-2.9], and OR 1.0 [95% CI 0.7-1.5], respectively). Among patients ages >= 65 years who underwent elective primary TKA at very-low-volume, low-volume, and high-volume hospitals, the ORs for 1-year mortality were significantly higher (OR 0.6 [95% CI 0.2-2.1], OR 1.6 [95% CI 1.0-2.4], and OR 0.9 [95% CI 0.6-1.3], respectively), compared with very-high-volume hospitals. Conclusion. Performance of elective primary THA and TKA surgeries in low-volume hospitals was associated with a higher risk of venous thromboembolism and mortality. Confounding due to unmeasured variables is possible. Modifiable system-based factors/processes should be targeted to reduce the number of complications associated with THA/TKA procedures. C1 [Singh, Jasvinder A.] Univ Alabama, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Rochester, MN USA. [Kwoh, C. Kent; Boudreau, Robert M.; Ibrahim, Said A.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Lee, Gwo-Chin; Ibrahim, Said A.] Univ Penn, Philadelphia, PA 19104 USA. [Ibrahim, Said A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Singh, JA (reprint author), Univ Alabama, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI Boudreau, Robert/0000-0003-0162-5187; singh, jasvinder/0000-0003-3485-0006 FU Western Pennsylvania Chapter of the Arthritis Foundation; NIH [1-KL2-RR-024151-01]; NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [K24-AR-055259] FX Supported by a pilot grant from the Western Pennsylvania Chapter of the Arthritis Foundation. Dr. Singh's work was supported by the NIH (Clinical Translational Science Award 1-KL2-RR-024151-01 to the Mayo Clinic Center for Clinical and Translational Research). Dr. Ibrahim's work was supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant K24-AR-055259). NR 29 TC 29 Z9 29 U1 0 U2 6 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 AUG PY 2011 VL 63 IS 8 BP 2531 EP 2539 DI 10.1002/art.30390 PG 9 WC Rheumatology SC Rheumatology GA 806US UT WOS:000293840200044 PM 21656509 ER PT J AU White, MB Lankarani-Fard, A AF White, Mary B. Lankarani-Fard, Azadeh TI What Is Your Diagnosis? SO CUTIS LA English DT Editorial Material ID CHRONIC ULCERS; DRUG-USERS C1 [White, Mary B.; Lankarani-Fard, Azadeh] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP White, MB (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 0011-4162 J9 CUTIS JI Cutis PD AUG PY 2011 VL 88 IS 2 BP 61 EP + PG 3 WC Dermatology SC Dermatology GA 810BI UT WOS:000294100000002 PM 21916270 ER PT J AU Deswal, A Richardson, P Bozkurt, B Mann, DL AF Deswal, Anita Richardson, Peter Bozkurt, Biykem Mann, Douglas L. TI Results of the Randomized Aldosterone Antagonism in Heart Failure With Preserved Ejection Fraction Trial (RAAM-PEF) SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Diastolic heart failure; diastolic function; exercise testing; treatment ID LEFT-VENTRICULAR DYSFUNCTION; 6-MINUTE WALK TEST; MYOCARDIAL FIBROSIS; DIASTOLIC FUNCTION; ESSENTIAL-HYPERTENSION; SERUM CONCENTRATIONS; COLLAGEN TURNOVER; SYSTOLIC FUNCTION; EPLERENONE; DISEASE AB Background: Cardiac fibrosis is a major determinant of myocardial stiffness, diastolic dysfunction, and heart failure (HF). By reducing cardiac fibrosis, aldosterone antagonists have the potential to be beneficial in heart failure with preserved ejection fraction (HFpEF). Methods and Results: In a randomized, double-blind, placebo-controlled trial of 44 patients with HFpEF, we examined the effects of eplerenone, an aldosterone antagonist, on changes in 6-minute walk distance (primary end point), diastolic function, and biomarkers of collagen turnover (secondary end points). All patients had a history of hypertension, 61% were diabetic, and 52% had prior HF hospitalization. After 6 months of treatment, similar improvements in 6 minute walk distance were noted in the eplerenone and placebo groups (P = .91). However, compared with placebo, eplerenone was associated with a significant reduction in serum markers of collagen turnover (procollagen type I aminoterminal peptide, P = .009 and carboxy-terminal telopeptide of collagen type I, P = .026) and improvement in echocardiographic measures of diastolic function (E/E', P = .01). Conclusions: Although eplerenone was not associated with an improvement in exercise capacity compared to placebo, it was associated with significant reduction in markers of collagen turnover and improvement in diastolic function. Whether these favorable effects will translate into morbidity and mortality benefit in HFpEF remains to be determined. (J Cardiac Fail 2011;17:634-642) C1 [Deswal, Anita; Bozkurt, Biykem] Michael E DeBakey VA Med Ctr, Winters Ctr Heart Failure Res, Cardiol Sect, Houston, TX USA. [Deswal, Anita; Richardson, Peter] Michael E DeBakey VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Mann, Douglas L.] Washington Univ, Sch Med, Div Cardiol, St Louis, MO USA. RP Deswal, A (reprint author), Michael E DeBakey VA Med Ctr 111B, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM adeswal@bcm.tmc.edu OI Mann, Douglas /0000-0002-2516-0145 FU VA Clinical Research Service [CLIN-010-03S] FX Supported by a VA Clinical Research Service grant # CLIN-010-03S (to Dr. Deswal). NR 34 TC 64 Z9 65 U1 0 U2 4 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2011 VL 17 IS 8 BP 634 EP 642 DI 10.1016/j.cardfail.2011.04.007 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 807YJ UT WOS:000293938600004 PM 21807324 ER PT J AU Fitzgerald, AA Powers, JD Ho, PM Maddox, TM Peterson, PN Allen, LA Masoudi, FA Magid, DJ Havranek, EP AF Fitzgerald, Ashley A. Powers, J. David Ho, P. Michael Maddox, Thomas M. Peterson, Pamela N. Allen, Larry A. Masoudi, Frederick A. Magid, David J. Havranek, Edward P. TI Impact of Medication Nonadherence on Hospitalizations and Mortality in Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; medication nonadherence; outcomes ID EVIDENCE-BASED PHARMACOTHERAPY; MYOCARDIAL-INFARCTION; PHARMACY RECORDS; OLDER PATIENTS; ADHERENCE; OUTCOMES; THERAPY; HYPERTENSION; PREDICTORS; SURVIVAL AB Background: Limited literature exists on the association between medication adherence and outcomes among patients with heart failure. Methods and Results: We conducted a retrospective longitudinal cohort study of 557 patients with heart failure with reduced ejection fraction (HFrEF) (defined by EF <50%) in a large health maintenance organization. We used multivariable Cox proportional hazards models to assess the relationship between adherence (with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and aldosterone antagonists) and the primary outcome of all-cause mortality plus cardiovascular hospitalizations. Mean follow-up time was 1.1 years. Nonadherence (defined as <80% adherence) was associated with a statistically significant increase in the primary outcome in the cohort overall (hazard ratio 2.07, 95% confidence interval 1.62-2.64; P < .0001). This association remained significant when all 3 classes of heart failure medications and the components of the composite end point were considered separately and when the adherence threshold was varied to 70% or 90%. Conclusions: Medication nonadherence was associated with an increased risk of all-cause mortality and cardiovascular hospitalizations in a community heart failure population. Further research is needed to define systems of care that optimize adherence among patients with heart failure. (J Cardiac Fail 2011; 17:664-669) C1 [Fitzgerald, Ashley A.; Ho, P. Michael; Maddox, Thomas M.] Denver VA Med Ctr, Div Cardiol, Denver, CO USA. [Fitzgerald, Ashley A.; Ho, P. Michael; Maddox, Thomas M.; Peterson, Pamela N.; Allen, Larry A.; Masoudi, Frederick A.; Havranek, Edward P.] Univ Colorado Denver, Sch Med, Div Cardiol, Denver, CO USA. [Powers, J. David; Ho, P. Michael; Peterson, Pamela N.; Masoudi, Frederick A.; Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Peterson, Pamela N.; Masoudi, Frederick A.; Havranek, Edward P.] Denver Hlth Med Ctr, Div Cardiol, Denver, CO USA. RP Fitzgerald, AA (reprint author), Univ Colorado Denver, Div Cardiol, 12631 E 17th Ave,Campus Box B-130, Aurora, CO 80045 USA. EM ashley.fitzgerald@ucdenver.edu NR 33 TC 59 Z9 59 U1 0 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2011 VL 17 IS 8 BP 664 EP 669 DI 10.1016/j.cardfail.2011.04.011 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 807YJ UT WOS:000293938600008 PM 21807328 ER PT J AU Reusch, JEB Wang, CCL AF Reusch, Jane E. B. Wang, Cecilia C. Low TI Cardiovascular Disease in Diabetes: Where Does Glucose Fit In? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID CORONARY-HEART-DISEASE; SMOOTH-MUSCLE-CELLS; AORTIC ENDOTHELIAL-CELLS; RISK-FACTOR; MYOCARDIAL-INFARCTION; SEVERE HYPOGLYCEMIA; ARTERY-DISEASE; FOLLOW-UP; EPIDEMIOLOGIC ANALYSIS; GLYCATED HEMOGLOBIN AB Context: Recent prospective clinical trials have failed to confirm a unique benefit from normalization of glycemia on cardiovascular disease outcomes, despite evidence from basic vascular biology, epidemiological, and cohort studies. Evidence Acquisition: The literature was searched using the http://www.ncbi.nlm.nih.gov search engine including over 20 million citations on MEDLINE (1970 to present). Keyword searches included: atherosclerosis, cardiovascular, and glucose. Epidemiological, cohort, and interventional data on cardiovascular disease outcomes and glycemic control were reviewed along with analysis of recent reviews on this topic. Evidence Synthesis: High glucose activates a proatherogenic phenotype in all cell types in the vessel wall including endothelial cells, vascular smooth muscle cells, inflammatory cells, fibroblasts, and platelets, leading to a feedforward atherogenic response. Epidemiological and Cohort Studies: Epidemiological and cohort evidence indicates a clear and consistent correlation of glycemia with cardiovascular disease. A recent report of over 25,000 subjects with diabetes in the Swedish National Diabetes Registry verifies this relationship in contemporary practice. Interventional Studies: Prospective randomized interventions targeting a hemoglobin A1c of 6-6.5% for cardiovascular disease prevention failed to consistently decrease cardiovascular events or all-cause mortality. Conclusions: Basic vascular biology data plus epidemiological and cohort evidence would predict that glucose control should impact cardiovascular events. Prospective clinical trials demonstrate that current strategies that improve blood glucose do not achieve this goal but suggest that a period of optimal control may confer long-term cardiovascular disease benefit. Clinicians should target a hemoglobin A1c of 7% for the prevention of microvascular complications, individualized to avoid hypoglycemia. (J Clin Endocrinol Metab 96: 2367-2376, 2011) C1 [Reusch, Jane E. B.] Denver VA Med Ctr, Denver, CO 80220 USA. Univ Colorado, Aurora, CO 80045 USA. RP Reusch, JEB (reprint author), Denver VA Med Ctr, Room 9C120B,Mailstop 111-H,1055 Clermont St, Denver, CO 80220 USA. EM jane.reusch@ucdenver.edu FU Veterans Administration Office of Research and Development; Career Development Award-2; National Institutes of Health [DK64741, HL56481, UL1 RR025780] FX This work was supported by Veterans Administration Office of Research and Development in the form of a Merit Award (to J.E.B.R.), by a Career Development Award-2 (to C.C.L.W.), and by the National Institutes of Health (Grants DK64741, HL56481, and UL1 RR025780 to J.E.B.R. and Grant UL1 RR025780 to C.C.L.W.). NR 69 TC 28 Z9 29 U1 0 U2 9 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2011 VL 96 IS 8 BP 2367 EP 2376 DI 10.1210/jc.2010-3011 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 802MT UT WOS:000293516400034 PM 21593112 ER PT J AU Dublin, S Anderson, ML Haneuse, SJ Heckbert, SR Crane, PK Breitner, JCS McCormick, W Bowen, JD Teri, L McCurry, SM Larson, EB AF Dublin, Sascha Anderson, Melissa L. Haneuse, Sebastien J. Heckbert, Susan R. Crane, Paul K. Breitner, John C. S. McCormick, Wayne Bowen, James D. Teri, Linda McCurry, Susan M. Larson, Eric B. TI Atrial Fibrillation and Risk of Dementia: A Prospective Cohort Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Scientific Meeting on the American-Geriatrics-Society CY MAY 13, 2010 CL Orlando, FL SP Amer Geriatr Soc DE atrial fibrillation; cardiac arrhythmia; dementia; Alzheimer disease; epidemiology ID CEREBRAL BLOOD-FLOW; OLDER PERSONS; COGNITIVE FUNCTION; APOLIPOPROTEIN-E; SELF-REPORT; STROKE; HYPERTENSION; PREVALENCE; INFARCTION; DECLINE AB OBJECTIVES: To determine whether atrial fibrillation (AF) is associated with risk of incident dementia or Alzheimer's disease (AD), beyond its effect on stroke. DESIGN: Prospective cohort study. SETTING: An integrated healthcare delivery system. PARTICIPANTS: A population-based sample of 3,045 community-dwelling adults aged 65 and older without dementia or clinical stroke followed from 1994 to 2008. MEASUREMENTS: AF was identified from health plan electronic data using International Classification of Diseases, Ninth Revision, codes from inpatient and outpatient encounters. Covariates came from self-report, study measures, and health plan data. Participants were screened every 2 years using the Cognitive Abilities Screening Instrument (range 0-100), with detailed neuropsychological and clinical assessment of those scoring less than 86. A multidisciplinary consensus committee determined diagnoses of all-cause dementia and possible or probable AD using standard research criteria. RESULTS: AF was present in 132 (4.3%) participants at baseline and was diagnosed in 370 (12.2%) more over a mean of 6.8 years of follow-up; 572 participants (18.8%) developed dementia (449 with AD). The adjusted hazard ratio associated with AF was 1.38 (95% confidence interval (CI) 51.10-1.73) for all-cause dementia and 1.50 (95% CI51.16-1.94) for possible or probable AD. Results were similar for participants with and without clinically recognized stroke during follow-up and in sensitivity analyses examining only probable AD. CONCLUSION: AF is associated with higher risk of developing AD and dementia. Future studies should examine whether specific treatments, including optimal anticoagulation, can decrease this risk. J Am Geriatr Soc 59: 1369-1375, 2011. C1 [Dublin, Sascha; Anderson, Melissa L.; Haneuse, Sebastien J.; Heckbert, Susan R.; McCurry, Susan M.; Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA 98101 USA. [Crane, Paul K.; Larson, Eric B.] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. [Breitner, John C. S.; McCormick, Wayne] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Dublin, Sascha; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Haneuse, Sebastien J.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Larson, Eric B.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Bowen, James D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Teri, Linda; McCurry, Susan M.] Univ Washington, Dept Psychosocial & Community Hlth, Seattle, WA 98195 USA. [Breitner, John C. S.; Teri, Linda; McCurry, Susan M.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Teri, Linda] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Breitner, John C. S.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Bowen, James D.] Swedish Neurosci Inst, Seattle, WA USA. RP Dublin, S (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM dub-lin.s@ghc.org RI Crane, Paul/C-8623-2014 OI Crane, Paul/0000-0003-4278-7465 FU NHLBI NIH HHS [2R01HL068986, R01 HL068986, R01 HL068986-03]; NIA NIH HHS [2U01AG006781-22A1, K23 AG028954, K23 AG028954-03, K23AG028954, U01 AG006781, U01 AG006781-22A1] NR 37 TC 48 Z9 50 U1 1 U2 7 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 AUG PY 2011 VL 59 IS 8 BP 1369 EP 1375 DI 10.1111/j.1532-5415.2011.03508.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 808MA UT WOS:000293980600001 PM 21806558 ER PT J AU Hanlon, JT Wang, XQ Castle, NG Stone, RA Handler, SM Semla, TP Pugh, MJ Berlowitz, DR Dysken, MW AF Hanlon, Joseph T. Wang, Xiaoqiang Castle, Nicholas G. Stone, Roslyn A. Handler, Steven M. Semla, Todd P. Pugh, Mary Jo Berlowitz, Dan R. Dysken, Maurice W. TI Potential Underuse, Overuse, and Inappropriate Use of Antidepressants in Older Veteran Nursing Home Residents SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the Gerontological-Society-of-America CY NOV 19-20, 2009 CL Atlanta, GA SP Gerontol Soc Amer DE aged; nursing homes; depression; pharmacoepidemiology ID MINIMUM DATA SET; LONG-TERM-CARE; COGNITIVE PERFORMANCE; RECOGNIZED DEPRESSION; MEDICATION; PREVALENCE; INTERVENTIONS; VALIDATION; MANAGEMENT; QUALITY AB OBJECTIVES: To examine prevalence and resident-and site-level factors associated with potential underuse, overuse, and inappropriate use of antidepressants in older Veterans Affairs (VA) Community Living Center (CLC) residents. DESIGN: Longitudinal study. SETTING: One hundred thirty-three VA CLCs. PARTICIPANTS: Three thousand six hundred ninety-two veterans aged 65 and older admitted between January 1, 2004, and June 3, 2005, with long stays (>= 90 days). MEASUREMENTS: Prevalence of potential underuse, inappropriate use, and overuse of antidepressants in residents with and without depression (as documented according to International Classification of Diseases, Ninth Revision, Clinical Modification, codes or Depression Rating Scale). RESULTS: Selective serotonin reuptake inhibitors were the most commonly prescribed antidepressant. Of the 877 residents with depression, 25.4% did not receive an antidepressant, suggesting potential underuse. Of residents with depression who received antidepressants, 57.5% had potential inappropriate use due primarily to problems seen with drug-drug and drug-disease interactions. Of the 2,815 residents who did not have depression, 1,190 (42.3%) were prescribed one or more antidepressants; only 48 (4.0%) of these had a Food and Drug Administration-approved labeled indication, suggesting potential overuse. Overall, only 17.6% of antidepressant use was appropriate (324/1,844). The only consistent resident factor associated with potential underuse and overuse use was taking an antipsychotic without evidence of schizophrenia (underuse: adjusted relative risk ratio (ARRR) = 0.56, 95% confidence interval (CI) = 0.33-0.94; overuse: adjusted odds ratio = 1.52, 95% CI = 1.21-1.91). Having moderate to severe pain (ARRR = 1.54, 95% CI = 1.08-2.20) and the prescribing of an anxiolytic or hypnotic (ARRR = 1.33, 95% CI = 1.02-1.74) increased the risk of potential inappropriate antidepressant use. CONCLUSION: Potential problems with the use of antidepressants were frequently observed in older U. S. veteran CLC residents. Future studies are needed to examine the true risks and benefits of antidepressant use in CLC and non-VA nursing homes. J Am Geriatr Soc 59: 1412-1420, 2011. C1 [Hanlon, Joseph T.; Handler, Steven M.] Vet Affairs Pittsburgh Hlth Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Hanlon, Joseph T.; Wang, Xiaoqiang; Stone, Roslyn A.; Handler, Steven M.] Vet Affairs Pittsburgh Hlth Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hanlon, Joseph T.; Handler, Steven M.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.; Handler, Steven M.] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Castle, Nicholas G.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15213 USA. [Stone, Roslyn A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA. [Semla, Todd P.] Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA. [Semla, Todd P.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Semla, Todd P.] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Pugh, Mary Jo] S Texas Vet Affairs Hlth Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. [Berlowitz, Dan R.] Ctr Hlth Qual Outcomes & Econ Res, Dept Vet Affairs, Bedford, MA USA. [Dysken, Maurice W.] Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, Minneapolis, MN USA. RP Hanlon, JT (reprint author), Univ Pittsburgh, Dept Geriatr Med, Kaufman Med Bldg Suite 514,3471 5th Ave, Pittsburgh, PA 15213 USA. EM jth14@pitt.edu OI Handler, Steven/0000-0002-3940-3224; Pugh, Mary Jo/0000-0003-4196-7763 FU AHRQ HHS [R01 HS017695, K12 HS019461, R01 HS018721]; NIA NIH HHS [3U01 AG012553, K07 AG033174, K07 AG033174-01A1, K07 AG033174-02, K07 AG033174-03, K07AG033174, P30 AG024827, P30AG024827, R01 AG034056, R01 AG034056-01, R01 AG034056-02, R01AG034056, R56 AG027017, R56 AG027017-04, R56AG027017, T32 AG021885, U01 AG012553]; NIMH NIH HHS [R34 MH082682]; NINR NIH HHS [R01 NR010135] NR 41 TC 28 Z9 30 U1 2 U2 9 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 AUG PY 2011 VL 59 IS 8 BP 1412 EP 1420 DI 10.1111/j.1532-5415.2011.03522.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 808MA UT WOS:000293980600006 PM 21824120 ER PT J AU Min, LC Reuben, DB Adams, J Shekelle, PG Ganz, DA Roth, CP Wenger, NS AF Min, Lillian C. Reuben, David B. Adams, John Shekelle, Paul G. Ganz, David A. Roth, Carol P. Wenger, Neil S. TI Does Better Quality of Care for Falls and Urinary Incontinence Result in Better Participant-Reported Outcomes? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE quality of care; urinary incontinence; falls ID NUTRITION EXAMINATION SURVEY; RANDOMIZED CONTROLLED-TRIAL; ELDERLY-PEOPLE; OLDER-ADULTS; URGE INCONTINENCE; NATIONAL-HEALTH; COMMUNITY; WOMEN; INTERVENTIONS; PROGRAM AB OBJECTIVES: To determine whether delivery of better quality of care for urinary incontinence (UI) and falls is associated with better participant-reported outcomes. DESIGN: Retrospective cohort study. SETTING: Assessing Care of Vulnerable Elders Study 2 (ACOVE-2). PARTICIPANTS: Older (>= 75) ambulatory care participants in ACOVE-2 who screened positive for UI (n = 133) or falls or fear of falling (n = 328). MEASUREMENTS: Composite quality scores (percentage of quality indicators (QIs) passed per participant) and change in Incontinence Quality of Life (IQOL, range 0-100) or Falls Efficacy Scale (FES, range 10-40) scores were measured before and after care was delivered (mean 10months). Because the treatment-related falls QIs were measured only on patients who received a physical examination, an alternative Common Pathway QI (CPQI) score was developed that assigned a failing score for falls treatment to unexamined participants. RESULTS: Each 10% increment in receipt of recommended care for UI was associated with a 1.4-point improvement in IQOL score (P = .01). The original falls composite quality-of-care score was unrelated to FES, but the new CPQI scoring method for falls quality of care was related to FES outcomes (10.4 points per 10% increment in falls quality, P = .01). CONCLUSION: Better quality of care for falls and UI was associated with measurable improvement in participant-reported outcomes in less than 1 year. The connection between process and outcome required consideration of the interdependence between diagnosis and treatment in the falls QIs. The link between process and outcome demonstrated for UI and falls underscores the importance of improving care in these areas. J Am Geriatr Soc 59:1435-1443, 2011. C1 [Min, Lillian C.] Univ Michigan, Sch Med, Div Geriatr, Ann Arbor, MI USA. [Min, Lillian C.] Ann Arbor Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Care Ctr, Ann Arbor, MI USA. [Min, Lillian C.; Adams, John; Shekelle, Paul G.; Roth, Carol P.; Wenger, Neil S.] RAND Hlth, Santa Monica, CA USA. [Reuben, David B.; Shekelle, Paul G.; Ganz, David A.; Wenger, Neil S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Shekelle, Paul G.; Ganz, David A.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Min, LC (reprint author), 300 N Ingalls Bldg,Wing E Room 966, Ann Arbor, MI 48109 USA. EM lmin@med.umich.edu FU Agency for Healthcare Research and Quality [R21 HS017621]; University of Michigan Claude Pepper Older Americans Independence Center; Geriatric Research, Education, and Clinical Care Center at the Veterans Administration Healthcare System in Ann Arbor; UCLA Claude Pepper Older Americans Independence Center (NIA-UCLA) [K12 AG001004]; U.S. Department of Veterans Affairs (VA), Veterans Health Administration, VA Health Services Research and Development (HSR&D) Service through the VA Greater Los Angeles HSR&D Center of Excellence [VA CD2 08-012-1]; Pfizer Inc FX Dr. Min is supported by the Agency for Healthcare Research and Quality (R21 HS017621); a Research Career Development Core award from the University of Michigan Claude Pepper Older Americans Independence Center; and the Geriatric Research, Education, and Clinical Care Center at the Veterans Administration Healthcare System in Ann Arbor. Dr. Min was on the University of California at Los Angeles (UCLA) faculty during the writing of this manuscript, supported by the UCLA Claude Pepper Older Americans Independence Center (NIA-UCLA K12 AG001004). Dr. Ganz is funded by the U.S. Department of Veterans Affairs (VA), Veterans Health Administration, VA Health Services Research and Development (HSR&D) Service through the VA Greater Los Angeles HSR&D Center of Excellence (Project VA CD2 08-012-1).; The original ACOVE-2 study was supported by a contract from Pfizer Inc to RAND. Pfizer did not serve a role in the design, analysis, or preparation of this retrospective analysis. NR 35 TC 13 Z9 13 U1 0 U2 6 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 AUG PY 2011 VL 59 IS 8 BP 1435 EP 1443 DI 10.1111/j.1532-5415.2011.03517.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 808MA UT WOS:000293980600009 PM 21806560 ER PT J AU Huang, AJ Brown, JS Boyko, EJ Moore, EE Scholes, D Walter, LC Lin, F Vittinghoff, E Fihn, SD AF Huang, Alison J. Brown, Jeanette S. Boyko, Edward J. Moore, Elya E. Scholes, Delia Walter, Louise C. Lin, Feng Vittinghoff, Eric Fihn, Stephan D. TI Clinical Significance of Postvoid Residual Volume in Older Ambulatory Women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE postvoid residual; urinary incontinence; urinary tract infection; nocturia ID SELF-RATED HEALTH; URINARY-INCONTINENCE; POSTMENOPAUSAL WOMEN; POPULATION; PREVALENCE; MANAGEMENT; ULTRASOUND; COMMUNITY; BLADDER; PERIMENOPAUSAL AB OBJECTIVES: To examine the prevalence, natural history, and clinical significance of high postvoid residual (PVR) volume in ambulatory older women. DESIGN: Prospective cohort study. SETTING: Group health plan in Washington state. PARTICIPANTS: Nine hundred eighty-seven ambulatory women aged 55 to 75. MEASUREMENTS: PVR was measured using bladder ultrasonography at baseline, 1 year, and 2 years. Participants completed questionnaires about urinary symptoms and provided urine samples for microbiological evaluation. RESULTS: Of the 987 participants, 79% had a PVR less than 50 mL, 10% of 50 to 99 mL, 6% of 100 to 199 mL, and 5% of 200 mL or greater at baseline. Of women with a PVR less than 50 mL, 66% reported at least one urinary symptom at baseline. Of women with a PVR of 200 mL or greater, 27% reported no significant symptoms at baseline. In adjusted analyses using data from all study visits, women with a PVR of 100 mL or greater were more likely to report urinating more than eight times during the day (odds ratio (OR) = 1.42, 95% confidence interval (CI) 51.07-1.87), and women with a PVR of 200 mL or greater were more likely to report weekly urgency incontinence (OR = 1.50, 95% CI = 1.03-2.18) than those with a PVR less than 50 mL. High PVR was not associated with greater risk of stress incontinence, nocturnal frequency, or urinary tract infection in adjusted analyses. Forty-six percent of those with a PVR of 200 mL or greater and 63% of those with a PVR of 100 to 199 mL at baseline had a PVR less than 50 mL at 2 years. CONCLUSION: More than 10% of ambulatory older women may have a PVR of 100 mL or greater, which is associated with greater risk of some urinary symptoms, but many with high PVR are asymptomatic, and high PVR frequently resolves within 2 years. Symptom-guided management of urinary symptoms may be more appropriate than PVR-guided management in this population. J Am Geriatr Soc 59:1452-1458, 2011. C1 [Huang, Alison J.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Brown, Jeanette S.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. [Lin, Feng; Vittinghoff, Eric] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Boyko, Edward J.] Univ Washington, Dept Med, Seattle, WA USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Moore, Elya E.] Royal Hosp Women, Dept Microbiol & Infect Dis, Melbourne, Vic, Australia. [Scholes, Delia] Grp Hlth Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA USA. [Walter, Louise C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Fihn, Stephan D.] Dept Vet Affairs, Washington, DC USA. RP Huang, AJ (reprint author), 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. EM ahuang@ucsfmed.org OI Boyko, Edward/0000-0002-3695-192X FU Pfizer, Inc., through University of California at San Francisco; National Institutes of Health (NIH) [RR024130, T32AI07140, RO1 DK43134]; Veterans Affairs Puget Sound Health Care System, Seattle, Washington FX Drs. Huang and Brown have received support for research related to urinary incontinence from Pfizer, Inc., through contracts with the University of California at San Francisco. No other authors have any potential conflicts of interest with regard to this research.; This research was supported by National Institutes of Health (NIH) Grants RR024130, T32AI07140, and RO1 DK43134 and by the resources and facilities at the Veterans Affairs Puget Sound Health Care System, Seattle, Washington. NR 38 TC 13 Z9 13 U1 0 U2 6 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 AUG PY 2011 VL 59 IS 8 BP 1452 EP 1458 DI 10.1111/j.1532-5415.2011.03511.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 808MA UT WOS:000293980600011 PM 21806559 ER PT J AU Min, L Ubhayakar, N Saliba, D Kelley-Quon, L Morley, E Hiatt, J Cryer, H Tillou, A AF Min, Lillian Ubhayakar, Nitin Saliba, Debra Kelley-Quon, Lorraine Morley, Eric Hiatt, Jonathan Cryer, Henry Tillou, Areti TI The Vulnerable Elders Survey-13 Predicts Hospital Complications and Mortality in Older Adults with Traumatic Injury: A Pilot Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE trauma; acute surgical care; functional status ID MAJOR TRAUMA; FUNCTIONAL DECLINE; GERIATRIC-PATIENTS; CARE; OUTCOMES; PEOPLE; VALIDATION; COMMUNITY; EMERGENCY; SEVERITY AB OBJECTIVES: To determine whether the Vulnerable Elders Survey (VES)-13, a survey based on functional status that has been validated in uninjured older populations, will predict complications and mortality in injured older adults. DESIGN: Prospective observational pilot study. SETTING: Level 1 trauma center. PARTICIPANTS: Sixty-three older adults (>= 65) with a traumatic injury who survived and required inpatient care for at least 24 hours. MEASUREMENTS: Predictor: preinjury VES-13 score (0-10 points, higher = greater risk) obtained by interviewing participants or proxies. Outcomes: composite outcome of one or more medical complications (e. g., aspiration pneumonia, respiratory failure) or death, discharge destination (home, nursing home, death), length of stay, hospital charges. Covariates: Charlson Comorbidity Index (CCI), Injury Severity Score (ISS), and sex. RESULTS: Of the 63 participants, 30 (48%) were discharged to home and 28 (44%) to a nursing facility, 21 (33%) developed one or more complications, and four (6%) died. In a model that also controlled for ISS and comorbidity, each additional VES-13 point was associated with greater risk of complication or death (odds ratio = 1.53 per point, 95% confidence interval = 1.12-2.07). CONCLUSION: The VES-13, in combination with injury severity, may be useful early in the hospital course to predict complications and death in older adults with traumatic C1 [Min, Lillian] Univ Michigan, Sch Med, Div Geriatr, Ann Arbor, MI 48109 USA. [Min, Lillian] Geriatr Res Educ & Clin Care Ctr, Dept Vet Affairs, Ann Arbor, MI USA. [Ubhayakar, Nitin] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Saliba, Debra] Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Care Ctr, Los Angeles, CA USA. [Saliba, Debra; Kelley-Quon, Lorraine; Hiatt, Jonathan; Cryer, Henry; Tillou, Areti] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Saliba, Debra; Kelley-Quon, Lorraine; Hiatt, Jonathan; Cryer, Henry; Tillou, Areti] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Saliba, Debra] Univ Calif Los Angeles Jewish Homes, Borun Ctr Gerontol Res, Los Angeles, CA USA. [Morley, Eric] Univ Calif Davis, Sch Med, Davis, CA 95616 USA. RP Min, L (reprint author), Univ Michigan, Sch Med, Div Geriatr, 300 N Ingalls Bldg, Ann Arbor, MI 48109 USA. EM lmin@med.umich.edu FU UCLA Claude D. Pepper Older American Independence Center; University of Michigan Pepper Center; American Geriatrics Society FX Drs. Min and Tillou were each supported by the Mentored Clinical Scientist Development Program in Geriatrics Awards sponsored by the UCLA Claude D. Pepper Older American Independence Center. Dr. Min is now supported by a Research Career Development Core Career Development Award from the University of Michigan Pepper Center. Dr. Tillou is supported by an American Geriatrics Society Dennis W. Jahnigen Career Development Award. Dr. Kelley-Quon is a Robert Wood Johnson Foundation Clinical Scholar at UCLA. Mr. Ubhayakar was a 2009 Medical Student Training in Aging Research Scholar at UCLA. NR 31 TC 19 Z9 19 U1 1 U2 2 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 AUG PY 2011 VL 59 IS 8 BP 1471 EP 1476 DI 10.1111/j.1532-5415.2011.03493.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 808MA UT WOS:000293980600014 PM 21718276 ER PT J AU Steinman, MA Handler, SM Gurwitz, JH Schiff, GD Covinsky, KE AF Steinman, Michael A. Handler, Steven M. Gurwitz, Jerry H. Schiff, Gordon D. Covinsky, Kenneth E. TI Beyond the Prescription: Medication Monitoring and Adverse Drug Events in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE adverse drug events; drug monitoring; aged ID EMERGENCY-DEPARTMENT VISITS; PATIENTS AFTER-DISCHARGE; AMBULATORY-CARE; RANDOMIZED-TRIAL; MANAGEMENT; THERAPY; INFORMATION; OUTPATIENTS; INITIATION; POTASSIUM AB Whether a person will suffer harm from a medication or how severe that harm will be is difficult to predict precisely. As a result, many adverse drug events (ADEs) occur in patients in whom it was reasonable to believe that the drug's benefits exceeded its risks. Improving safety and reducing the burden of ADEs in older adults requires addressing this uncertainty by not only focusing on the appropriateness of the initial prescribing decision, but also by detecting and mitigating adverse events once they have started to occur. Such enhanced monitoring of signs, symptoms, and laboratory parameters can determine whether an adverse event has only mild and short-term consequences or major long-term effects on morbidity and mortality. Although current medication monitoring practices are often suboptimal, several strategies can be leveraged to improve the quality and outcomes of monitoring. These strategies include using health information technology to link pharmacy and laboratory data, prospective delineation of risk, and patient outreach and activation, all within a framework of team-based approaches to patient management. Although many of these strategies are theoretically possible now, they are poorly used and will be difficult to implement without a significant restructuring of medical practice. An enhanced focus on medication monitoring will also require a new conceptual framework to re-engineer the prescribing process. With this approach, prescribing quality does not hinge on static attributes of the initial prescribing decision but entails a dynamic process in which the benefits and harms of drugs are actively monitored, managed, and reassessed over time. J Am Geriatr Soc 59:1513-1520, 2011. C1 [Steinman, Michael A.; Covinsky, Kenneth E.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Steinman, Michael A.; Covinsky, Kenneth E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Handler, Steven M.] Univ Pittsburgh, Dept Biomed Informat, Div Geriatr Med, Pittsburgh, PA 15260 USA. [Handler, Steven M.] Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Gurwitz, Jerry H.] Univ Massachusetts, Sch Med, Div Geriatr Med, Worcester, MA USA. [Gurwitz, Jerry H.] Meyers Primary Care Inst, Worcester, MA USA. [Schiff, Gordon D.] Harvard Univ, Sch Med, Div Gen Internal Med, Boston, MA USA. [Schiff, Gordon D.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Steinman, MA (reprint author), 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu OI Handler, Steven/0000-0002-3940-3224 FU National Institute on Aging (NIA) [1K24AG029812-02]; American Federation for Aging Research [1K23AG030999]; National Institutes of Health [5KL2RR024151]; Agency for Healthcare Research and Quality (AHRQ) [1R01HS018721-01]; [U18HS016973] FX Funding for this work was provided by a Beeson Career Development Award from the National Institute on Aging (NIA) and the American Federation for Aging Research (1K23AG030999, Dr. Steinman), a National Institutes of Health Roadmap Multidisciplinary Clinical Research Career Development Award (5KL2RR024151, Dr. Handler), a grant from the Agency for Healthcare Research and Quality (AHRQ) (1R01HS018721-01; Dr. Handler), a grant to the University of Illinois at Chicago Center for Education and Research in Therapeutics (U18HS016973, Dr. Schiff), and an award from the NIA (1K24AG029812-02, Dr. Covinsky). NR 50 TC 52 Z9 54 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 AUG PY 2011 VL 59 IS 8 BP 1513 EP 1520 DI 10.1111/j.1532-5415.2011.03500.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 808MA UT WOS:000293980600021 PM 21797831 ER PT J AU Phillips, GS Bhargava, P Stanescu, L Dick, AA Parnell, SE AF Phillips, Grace S. Bhargava, Puneet Stanescu, Luana Dick, Andre A. Parnell, Shawn E. TI Pediatric intestinal transplantation: normal radiographic appearance and complications SO PEDIATRIC RADIOLOGY LA English DT Article DE Intestinal transplantation; Intestinal failure; Short gut syndrome; Transplant complications; Children ID HEPATIC-ARTERY THROMBOSIS; SMALL-BOWEL TRANSPLANTS; LIVER-TRANSPLANTATION; ENDOVASCULAR TREATMENT; MULTIVISCERAL TRANSPLANTATION; IMAGING FINDINGS; PORTAL-VEIN; CHILDREN; STENOSIS; SPECTRUM AB We present a pictorial essay on pediatric intestinal transplantation that describes the indications for pediatric intestinal transplantation, surgical technique, and the role of imaging in the pre-transplant work-up and detection of post-transplant complications. We illustrate the normal post-transplant imaging appearance and common complications, including rejection, infection, post-transplant lymphoproliferative disease (PTLD), mechanical dysfunction and vascular complications. We conclude with an imaging algorithm for suspected post-transplant complications based on clinical scenarios. C1 [Phillips, Grace S.; Stanescu, Luana; Parnell, Shawn E.] Univ Washington, Dept Radiol, Seattle Childrens Hosp, Seattle, WA 98105 USA. [Bhargava, Puneet] Univ Washington, Dept Radiol, VA Puget Sound Hlth Care Syst, Seattle, WA 98105 USA. [Dick, Andre A.] Univ Washington, Dept Surg, Seattle Childrens Hosp, Seattle, WA 98105 USA. RP Phillips, GS (reprint author), Univ Washington, Dept Radiol, Seattle Childrens Hosp, 4800 Sandpoint Way NE, Seattle, WA 98105 USA. EM grace.phillips@seattlechildrens.org RI Bhargava, Puneet /F-1330-2011 OI Bhargava, Puneet/0000-0002-3849-9666 NR 32 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD AUG PY 2011 VL 41 IS 8 BP 1028 EP 1039 DI 10.1007/s00247-011-2094-3 PG 12 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 806CD UT WOS:000293779400013 PM 21607597 ER PT J AU Kilbourne, AM Pirraglia, PA Lai, ZS Bauer, MS Charns, MP Greenwald, D Welsh, DE McCarthy, JF Yano, EM AF Kilbourne, Amy M. Pirraglia, Paul A. Lai, Zongshan Bauer, Mark S. Charns, Martin P. Greenwald, Devra Welsh, Deborah E. McCarthy, John F. Yano, Elizabeth M. TI Quality of General Medical Care Among Patients With Serious Mental Illness: Does Colocation of Services Matter? SO PSYCHIATRIC SERVICES LA English DT Article ID HEALTH-CARE; CARDIOVASCULAR-DISEASE; NATIONAL-SURVEY; DISORDERS; VETERANS; INDIVIDUALS; ADULTS AB Objective: This study was conducted to determine whether patients with serious mental illness receiving care in Veterans Affairs (VA) mental health programs with colocated general medical clinics were more likely to receive adequate medical care than patients in programs without colocated clinics based on a nationally representative sample. Methods: The study included all VA patients with diagnoses of serious mental illness in fiscal year (FY) 2006-2007 who were also part of the VA's External Peer Review Program (EPRP) FY 2007 random sample and who received care from VA facilities (N=107 facilities) with organizational data from the VA Mental Health Program Survey (N=7,514).EPRP included patient-level chart review quality indicators for common processes of care (foot and retinal examinations for diabetes complications; screens for colorectal health, breast cancer, and alcohol misuse; and tobacco counseling) and outcomes (hypertension, diabetes blood sugar, and lipid control). Results: Ten out of 107 (10%) mental health programs had colocated medical clinics. After adjustment for organizational and patient-level factors, analyses showed that patients from colocated clinics compared with those without colocation were more likely to receive foot exams (OR=1.87, p<.05), colorectal cancer screenings (OR=1.54, p<.01), and alcohol misuse screenings (OR=2.92, p<.01). They were also more likely to have good blood pressure control (<140/90 mmHg; OR=1.32, p<.05) but less likely to have glycosylated hemoglobin <9% (OR=.69, p<.05). Conclusions: Colocation of medical care was associated with better quality of care for four of nine indicators. Additional strategies, particularly those focused on improving diabetes control and other chronic medical outcomes, might be warranted for patients with serious mental illness. (Psychiatric Services 62:922-928, 2011) C1 [Kilbourne, Amy M.; Lai, Zongshan; Welsh, Deborah E.; McCarthy, John F.] Dept Vet Affairs VA Ann Arbor, Serious Mental Illness Treatment Resource & Evalu, Ann Arbor, MI 48105 USA. [Pirraglia, Paul A.] Providence VA Med Ctr, Providence, RI USA. [Bauer, Mark S.; Charns, Martin P.] VA Boston Ctr Org Management & Leadership Res, Boston, MA USA. [Greenwald, Devra] VA Pittsburgh, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Yano, Elizabeth M.] VA Greater Los Angeles, HSR&D Ctr Excellence, Los Angeles, CA USA. RP Kilbourne, AM (reprint author), Dept Vet Affairs VA Ann Arbor, Serious Mental Illness Treatment Resource & Evalu, 11H,2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM amykilbo@umich.edu FU VA Health Services Research and Development Service [07-115]; National Institute of Mental Health [R34 MH74509] FX This work was supported by grant 07-115 from the VA Health Services Research and Development Service and by grant R34 MH74509 from the National Institute of Mental Health. The authors acknowledge the VA Office of Quality and Performance for providing access to the VA EPRP data. The views expressed in this article are those of the authors and do not necessarily represent the views of the VA. NR 29 TC 17 Z9 17 U1 2 U2 3 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 AUG PY 2011 VL 62 IS 8 BP 922 EP 928 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 800CP UT WOS:000293336900014 PM 21807832 ER PT J AU Lu, MW Duckart, JP O'Malley, JP Dobscha, SK AF Lu, Mary W. Duckart, Jonathan P. O'Malley, Jean P. Dobscha, Steven K. TI Correlates of Utilization of PTSD Specialty Treatment Among Recently Diagnosed Veterans at the VA SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; COMORBIDITY SURVEY REPLICATION; COGNITIVE PROCESSING THERAPY; MENTAL-HEALTH TREATMENT; UNITED-STATES; ADMINISTRATIVE DATA; TREATMENT-SEEKING; CARE; EPIDEMIOLOGY; AFGHANISTAN AB Objectives: This study described utilization of specialty treatment for posttraumatic stress disorder (PTSD) at U.S. Department of Veterans Affairs (VA) facilities among veterans of Operation Enduring Freedom (OEF), in Afghanistan, or of Operation Iraqi Freedom (OIF), in Iraq, and non-OEF-OIF veterans recently diagnosed as having PTSD. It also identified predictors of receiving minimally adequate specialty treatment, defined as attending at least nine clinic visits within 365 days of screening positive for PTSD. Methods: VA administrative data were obtained for 869 veterans who screened positive for PTSD between November 7, 2006, and September 30, 2008, received a diagnosis of PTSD, and visited a PTSD specialty clinic operated by the VA in the Pacific Northwest at least once within a year of screening positive. Results: A total of 286 (33%) of the 852 veterans for whom complete data were available received minimally adequate specialty treatment; OEF-OIF veterans were less likely than non-OEF-OIF veterans to receive minimally adequate specialty treatment (29% versus 36%, p=.021) and attended fewer mean +/- SD visits to a PTSD clinic (8.2 +/- 11.4 versus 9.9 +/- 13.5, p=.045). Predictors of receiving minimally adequate specialty treatment included attending a PTSD clinic visit within 30 days of a positive screen, living in an urban location, and having psychiatric comorbidities. Conclusions: Most veterans with new PTSD diagnoses who initiated VA PTSD specialty care did not receive minimally adequate specialty treatment. Future studies should examine factors that lead to premature discontinuation of PTSD treatment and to what extent specialty treatment for PTSD is necessary. (Psychiatric Services 62:943-949, 2011) C1 [Lu, Mary W.] Portland VA Med Ctr, Mental Hlth & Neurosci Div, Portland, OR 97239 USA. [Duckart, Jonathan P.; Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, Portland, OR 97239 USA. [Lu, Mary W.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Inst, Dept Psychiat, Portland, OR USA. [O'Malley, Jean P.] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Inst, Biostat & Design Program, Portland, OR USA. RP Lu, MW (reprint author), Portland VA Med Ctr, Mental Hlth & Neurosci Div, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM mary.lu@va.gov RI Schueter, nicos/A-3625-2014 FU VA Health Services Research and Development Service [REA 06-174]; Pacific Northwest Mental Illness Research and Education and Clinical Center FX This work was supported by VA Health Services Research and Development Service projects REA 06-174 and the Pacific Northwest Mental Illness Research and Education and Clinical Center. 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. The authors acknowledge James M. Sardo, Ph.D., Miles E. McFall, Ph.D., Larry Dewey, M.D., William Minium, and Sara Smucker-Barnwell, Ph.D., for assistance in gathering information about facility PTSD services; Michael C. Leo, Ph.D., for statistical consultation; and Lauren M. Denneson, Ph.D., for editorial assistance. NR 31 TC 35 Z9 35 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 AUG PY 2011 VL 62 IS 8 BP 943 EP 949 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 800CP UT WOS:000293336900017 PM 21807835 ER PT J AU Ayanbule, F Belaguli, NS Berger, DH AF Ayanbule, Funmi Belaguli, Narasimhaswamy S. Berger, David H. TI GATA Factors in Gastrointestinal Malignancy SO WORLD JOURNAL OF SURGERY LA English DT Article ID MUCIN GENE-EXPRESSION; TRANSCRIPTION FACTORS GATA-4; DNA-BINDING PROTEIN; SPASMOLYTIC POLYPEPTIDE PSP; IN-SITU HYBRIDIZATION; HEART TUBE FORMATION; CANCER CELL-LINE; PLASMINOGEN-ACTIVATOR; COLORECTAL-CANCER; BARRETTS-ESOPHAGUS AB GATA factors are unique transcription factors with conserved DNA-binding domains. They serve diverse roles in embryogenesis, cell differentiation, regulation of tissue-specific genes, and carcinogenesis. The subfamily GATA-4, -5, and -6 are highly expressed in endoderm-derived organs and regulate multiple gut-specific genes. Multiple studies have analyzed the role of GATA factors in gastrointestinal (GI) malignancy, such as those of the stomach, pancreas, and colon, and premalignant lesions such as Barrett's esophagus. The GATA factors appear to have distinct roles in regulating key genes involved in GI malignancy. Understanding the precise role of GATA factors in malignancy may lead to the development of effective molecular targets for cancer therapy. C1 [Ayanbule, Funmi; Belaguli, Narasimhaswamy S.; Berger, David H.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. RP Berger, DH (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM dhb@bcm.edu NR 120 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD AUG PY 2011 VL 35 IS 8 BP 1757 EP 1765 DI 10.1007/s00268-010-0950-1 PG 9 WC Surgery SC Surgery GA 805CZ UT WOS:000293705300009 PM 21210118 ER PT J AU Byrd, JB Zeng, C Tavel, HM Magid, DJ O'Connor, PJ Margolis, KL Selby, JV Ho, PM AF Byrd, James B. Zeng, Chan Tavel, Heather M. Magid, David J. O'Connor, Patrick J. Margolis, Karen L. Selby, Joe V. Ho, P. Michael TI Combination therapy as initial treatment for newly diagnosed hypertension SO AMERICAN HEART JOURNAL LA English DT Article ID JOINT NATIONAL COMMITTEE; HIGH BLOOD-PRESSURE; UNCOMPLICATED HYPERTENSION; 7TH REPORT; TRIAL; PRESCRIPTIONS; PREVENTION; VISITS AB Background The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends that clinicians consider the use of multidrug therapy to increase likelihood of achieving blood pressure goal. Little is known about recent patterns of combination antihypertensive therapy use in patients being initiated on hypertension treatment. Methods We investigated combination antihypertensive therapy use in newly diagnosed hypertensive patients from the Cardiovascular Research Network Hypertension Registry. Multivariable logistic regression was used to assess the relationship between combination antihypertensive therapy and 12-month blood pressure control. Results Between 2002 and 2007, a total of 161,585 patients met criteria for incident hypertension and were initiated on treatment. During the study period, an increasing proportion of patients were treated initially with combination rather than with single-agent therapy (20.7% in 2002 compared with 35.8% in 2007, P < .001). This increase in combination therapy use was more pronounced in patients with stage 2 hypertension, whose combination therapy use increased from 21.6% in 2002 to 44.5% in 2007. Nearly 90% of initial combination therapy was accounted for by 2 combinations, a thiazide and a potassium-sparing diuretic (47.6%) and a thiazide and an angiotensin-converting enzyme inhibitor (41.4%). After controlling for relevant clinical factors, including subsequent intensification of treatment and medication adherence, combination therapy was associated with increased odds of blood pressure control at 12 months (odds ratio compared with single-drug initial therapy 1.20; 95% CI 1.15-1.24, P < .001). Conclusions Initial treatment of hypertension with combination therapy is increasingly common and is associated with better long-term blood pressure control. (Am Heart J 2011;162:340-6.) C1 [Byrd, James B.] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. [Zeng, Chan; Tavel, Heather M.; Magid, David J.] Kaiser Permanente, Inst Hlth Res, Denver, CO USA. [O'Connor, Patrick J.; Margolis, Karen L.] HealthPartners Res Fdn, Minneapolis, MN USA. [Selby, Joe V.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Ho, P. Michael] Denver VA Med Ctr, Med Serv, Denver, CO USA. [Ho, P. Michael] Wellpoint Inc, Indianapolis, IN USA. RP Byrd, JB (reprint author), 12631 E 17th Ave B130, Aurora, CO 80045 USA. EM brian.byrd@ucdenver.edu OI Byrd, J. Brian/0000-0002-0509-3520 FU National Heart, Lung, and Blood Institute as part of the Cardiovascular Research Network [U19HL091179]; Veterans Affairs Research & Development Career Development Award [05-026-2]; Department of Veterans Affairs FX This study was funded by grant U19HL091179 from the National Heart, Lung, and Blood Institute as part of the Cardiovascular Research Network. Dr Ho is supported by a Veterans Affairs Research & Development Career Development Award (05-026-2). Dr Byrd was supported by a Department of Veterans Affairs Cardiology Research Fellowship. NR 14 TC 19 Z9 21 U1 0 U2 4 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 AUG PY 2011 VL 162 IS 2 BP 340 EP 346 DI 10.1016/j.ahj.2011.05.010 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 805MB UT WOS:000293729400018 PM 21835296 ER PT J AU Hage, FG Dean, P Bhatia, V Iqbal, F Heo, J Iskandrian, AE AF Hage, Fadi G. Dean, Phillip Bhatia, Vikas Iqbal, Fahad Heo, Jaekyeong Iskandrian, Ami E. TI The prognostic value of the heart rate response to adenosine in relation to diabetes mellitus and chronic kidney disease SO AMERICAN HEART JOURNAL LA English DT Article ID EMISSION COMPUTED-TOMOGRAPHY; STAGE RENAL-DISEASE; CARDIOVASCULAR AUTONOMIC NEUROPATHY; STRESS MYOCARDIAL-PERFUSION; CORONARY-ARTERY DISEASE; SUDDEN CARDIAC DEATH; RISK; MORTALITY; IMPACT; ASSOCIATION AB Background Myocardial perfusion imaging (MPI) is a useful method for risk assessment in patients with diabetes mellitus (DM) and chronic kidney disease (CKD), but these patients have a residual risk that is not accounted for by MPI. The objective of this study is to determine whether the heart rate response (HRR) to adenosine has an incremental prognostic value to MPI in high-risk patients. Methods The study group included 879 (age 61 +/- 13 years, 48% women, 58% white, 40% DM, 49% CKD) consecutive patients who underwent adenosine MPI. Chronic kidney disease was defined as an estimated glomerular filtration rate b60 mL/min per 1.73 m(2) or dialysis replacement therapy. An HRR <10% (change from baseline) was considered blunted. The outcome of interest was overall mortality. Results During a follow-up period of 40 +/- 14 months, 212 patients (24%) died. Patients with DM (23.4% +/- 16.3% vs 29.4% +/- 21.4%, P < .0001) and CKD (22.7% +/- 17.6% vs 30.5% +/- 20.4%, P < .0001) had lower HRR as compared with patients without DM and CKD, respectively. A blunted HRR was associated with increased mortality in the overall population and in those with DM and CKD and helped in risk stratification when added to traditional MPI findings. In a Cox regression model, a blunted HRR was the strongest predictor of mortality (hazard ratio 2.8, P < .0001) and provided additional prognostic data to MPI (hazard ratio 1.9, P < .0001) after controlling for age, gender, race, history of myocardial infarction, DM, CKD, beta-blocker use, and presence of chest pain. Conclusions A blunted HRR to adenosine is an independent predictor of poor outcome, adds incremental value to MPI, and helps in better risk stratification in high-risk patient groups. (Am Heart J 2011;162:356-62.) C1 [Hage, Fadi G.; Iqbal, Fahad; Heo, Jaekyeong; Iskandrian, Ami E.] Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. [Dean, Phillip; Bhatia, Vikas] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. RP Hage, FG (reprint author), Zeigler Res Bldg 1024,1530 3rd AVE S, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 26 TC 18 Z9 18 U1 0 U2 3 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 AUG PY 2011 VL 162 IS 2 BP 356 EP 362 DI 10.1016/j.ahj.2011.05.014 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 805MB UT WOS:000293729400020 PM 21835298 ER PT J AU McCurdy, SM Dai, QX Zhang, JH Zamilpa, R Ramirez, TA Dayah, T Nguyen, N Jin, YF Bradshaw, AD Lindsey, ML AF McCurdy, Sarah M. Dai, Qiuxia Zhang, Jianhua Zamilpa, Rogelio Ramirez, Trevi A. Dayah, Tariq Nguyen Nguyen Jin, Yu-Fang Bradshaw, Amy D. Lindsey, Merry L. TI SPARC mediates early extracellular matrix remodeling following myocardial infarction SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cardiac fibroblasts; left ventricular remodeling; mice; secreted protein, acidic, and rich in cysteine ID CYSTEINE SPARC; PROTEIN; HEART; MATRIX-METALLOPROTEINASE-9; FIBROBLASTS; MODEL; RICH AB McCurdy SM, Dai Q, Zhang J, Zamilpa R, Ramirez TA, Dayah T, Nguyen N, Jin YF, Bradshaw AD, Lindsey ML. SPARC mediates early extracellular matrix remodeling following myocardial infarction. Am J Physiol Heart Circ Physiol 301: H497-H505, 2011. First published May 20, 2011; doi:10.1152/ajpheart.01070.2010.-Secreted protein, acidic, and rich in cysteine (SPARC) is a matricellular protein that functions in the extracellular processing of newly synthesized collagen. Collagen deposition to form a scar is a key event following a myocardial infarction (MI). Because the roles of SPARC in the early post-MI setting have not been defined, we examined age-matched wild-type (WT; n = 22) and SPARC-deficient (null; n = 25) mice at day 3 post-MI. Day 0 WT (n = 28) and null (n = 20) mice served as controls. Infarct size was 52 +/- 2% for WT and 47 +/- 2% for SPARC null (P = NS), indicating that the MI injury was comparable in the two groups. By echocardiography, WT mice increased end-diastolic volumes from 45 +/- 2 to 83 +/- 5 mu l (P < 0.05). SPARC null mice also increased end-diastolic volumes but to a lesser extent than WT (39 +/- 3 to 63 +/- 5 mu l; P < 0.05 vs. day 0 controls and vs. WT day 3 MI). Ejection fraction fell post-MI in WT mice from 57 +/- 2 to 19 +/- 1%. The decrease in ejection fraction was attenuated in the absence of SPARC (65 +/- 2 to 28 +/- 2%). Fibroblasts isolated from SPARC null left ventricle (LV) showed differences in the expression of 22 genes encoding extracellular matrix and adhesion molecule genes, including fibronectin, connective tissue growth factor (CTGF; CCN2), matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of metalloproteinase-2 (TIMP-2). The change in fibroblast gene expression levels was mirrored in tissue protein extracts for fibronectin, CTGF, and MMP-3 but not TIMP-2. Combined, the results of this study indicate that SPARC deletion preserves LV function at day 3 post-MI but may be detrimental for the long-term response due to impaired fibroblast activation. C1 [McCurdy, Sarah M.; Dai, Qiuxia; Zhang, Jianhua; Zamilpa, Rogelio; Ramirez, Trevi A.; Dayah, Tariq; Lindsey, Merry L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Cardiol, San Antonio, TX 78229 USA. [Nguyen Nguyen; Jin, Yu-Fang] Univ Texas San Antonio, Dept Elect & Comp Engn, San Antonio, TX USA. [Bradshaw, Amy D.] Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, Charleston, SC 29425 USA. [Bradshaw, Amy D.] Ralph H Johnson Vet Adm, Charleston, SC USA. RP Lindsey, ML (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Cardiol, 7703 Floyd Curl Dr,Mail Code 7872, San Antonio, TX 78229 USA. EM lindseym@uthscsa.edu RI Lindsey, Merry/B-2650-2012 FU National Institute of Biomedical Imaging and Bioengineering [1R03-EB-009496]; National Heart, Lung, and Blood Institute [SC2-HL-101430, 2P01-HL-48788, HL-094517, R01-HL-75360]; Veteran's Administration; American Heart Association [AHA 0855119F]; Max and Minnie Tomerlin Voelcker Fund; American Physiological Society FX Support for this study was provided by National Institute of Biomedical Imaging and Bioengineering Grant 1R03-EB-009496 and National Heart, Lung, and Blood Institute Grant SC2-HL-101430 (to Y. Jin); National Heart, Lung, and Blood Institute Grants 2P01-HL-48788 and HL-094517 and a Veteran's Administration Merit Award (to A. D. Bradshaw); and National Heart, Lung, and Blood Institute Grant R01-HL-75360, the American Heart Association AHA 0855119F, and the Max and Minnie Tomerlin Voelcker Fund (to M. L. Lindsey). S. M. McCurdy was supported in 2008 by the American Physiological Society Summer Undergraduate Research Fellowship. NR 21 TC 28 Z9 30 U1 0 U2 3 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 AUG PY 2011 VL 301 IS 2 BP H497 EP H505 DI 10.1152/ajpheart.01070.2010 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 801MQ UT WOS:000293443800026 PM 21602472 ER PT J AU Mahajan, H Spaeth, DM Dicianno, BE Collins, DM Boninger, ML Cooper, RA AF Mahajan, Harshal Spaeth, Donald M. Dicianno, Brad E. Collins, Diane M. Boninger, Michael L. Cooper, Rory A. TI Comparison of Virtual Wheelchair Driving Performance of People With Traumatic Brain Injury Using an Isometric and a Conventional Joystick SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Assistive technology; Brain injuries, traumatic; Rehabilitation; User-computer interface; Wheelchairs, computer simulation ID ELECTRIC-POWERED WHEELCHAIRS; TARGET ACQUISITION; TECHNOLOGY; DISABILITIES; INDIVIDUALS; WORLDS AB Mahajan H, Spaeth DM, Dicianno BE, Collins DM, Boninger ML, Cooper RA. Comparison of virtual wheelchair driving performance of people with traumatic brain injury using an isometric and a conventional joystick. Arch Phys Med Rehabil 2011;92:1298-304. Objective: To compare wheelchair driving performance in a driving simulator using a conventional joystick and an isometric joystick. Design: Randomized, cohort study. Setting: A research facility based in a hospital or in an independent living center. Participants: Participants (N=20; 12 men, 8 women; mean age +/- SD, 30.62 +/- 10.91y) who were at least 1 year post-TBI. Interventions: Driving performance using an isometric joystick compared with a conventional movement joystick. Main Outcome Measures: Average trial completion time, and trajectory-specific measures measured orthogonal to the center of driving tasks: root mean squared error, movement offset, movement error, and number of significant changes in heading. Results: After statistically controlling for driving speed, participants were able to complete the driving tasks faster with an isometric joystick than while using a conventional movement joystick. Compared with the conventional joystick, an isometric joystick used for driving forward demonstrated fewer driving errors. During reverse driving the conventional joystick performed better. Conclusions: The customizable isometric joystick seems to be a promising interface for driving a powered wheelchair for individuals with TBI. C1 [Mahajan, Harshal; Spaeth, Donald M.; Dicianno, Brad E.; Boninger, Michael L.; Cooper, Rory A.] VA Pittsburgh HealthCare Syst, Human Engn Res Lab, Pittsburgh, PA 15206 USA. [Mahajan, Harshal; Spaeth, Donald M.; Dicianno, Brad E.; Boninger, Michael L.; Cooper, Rory A.] VA Pittsburgh HealthCare Syst, Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA 15206 USA. [Dicianno, Brad E.; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Mahajan, Harshal; Spaeth, Donald M.; Dicianno, Brad E.; Collins, Diane M.; Boninger, Michael L.; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Dicianno, Brad E.; Boninger, Michael L.; Cooper, Rory A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh HealthCare Syst, Human Engn Res Lab, 7180 Highland Dr,Bldg 4,2nd Fl E,151R1-H, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu OI Boninger, Michael/0000-0001-6966-919X; Dicianno, Brad/0000-0003-0738-0192 FU National Institute on Disability and Rehabilitation Research; U.S. Department of Education [H133A020502]; Human Engineering Research Laboratories, VA Pittsburgh HealthCare System FX Supported by the National Institute on Disability and Rehabilitation Research, U.S. Department of Education (grant no. H133A020502), and with resources and facilities by the Human Engineering Research Laboratories, VA Pittsburgh HealthCare System. The contents of this publication do not represent the views of the Department of Veterans Affairs or the United States Government. NR 25 TC 8 Z9 8 U1 4 U2 15 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 AUG PY 2011 VL 92 IS 8 BP 1298 EP 1304 DI 10.1016/j.apmr.2011.03.011 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 803WL UT WOS:000293612800016 PM 21807150 ER PT J AU Grubaugh, AL Zinzow, HM Paul, L Egede, LE Frueh, BC AF Grubaugh, Anouk L. Zinzow, Heidi M. Paul, Lisa Egede, Leonard E. Frueh, B. Christopher TI Trauma exposure and posttraumatic stress disorder in adults with severe mental illness: A critical review SO CLINICAL PSYCHOLOGY REVIEW LA English DT Review DE Posttraumatic stress disorder (PTSD); Severe mental illness (SMI); Trauma; Victimization; Psychotic; Bipolar ID NATIONAL COMORBIDITY SURVEY; SCHIZOPHRENIA SPECTRUM DISORDERS; SUBSTANCE USE DISORDERS; PSYCHIATRIC INPATIENT POPULATION; COGNITIVE-BEHAVIORAL TREATMENT; RANDOMIZED CONTROLLED-TRIAL; CHILDHOOD SEXUAL-ABUSE; QUALITY-OF-LIFE; CYCLING BIPOLAR DISORDER; ADMINISTERED PTSD SCALE AB There is a great deal of research on the prevalence, correlates, and treatment of PTSD in the general population. However, we know very little about the manifestation and consequences of PTSD in more complicated patient populations. The purpose of the current paper is to provide a comprehensive review of PTSD within the context of severe mental illness (SMI; i.e., schizophrenia spectrum disorders, mood disorders). Extant data suggest that trauma and PTSD are highly prevalent among individuals with SMI relative to the general population, and both are associated with adverse clinical functioning and increased healthcare burden. However, trauma and PTSD remain overlooked in this population, with low recognition rates in public-sector settings. Additionally, there are few data on the clinical course and treatment of PTSD among individuals with SMI. Particularly lacking are longitudinal studies, randomized controlled treatment trials, and studies using ethno-racially diverse samples. Furthermore, there is a need to better understand the interplay between trauma. PTSD, and severe forms of mental illness and to further develop and disseminate evidence-based PTSD treatments in this population. The current state of the literature and future directions for practice are discussed. Published by Elsevier Ltd. C1 [Grubaugh, Anouk L.; Paul, Lisa] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Grubaugh, Anouk L.; Egede, Leonard E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Zinzow, Heidi M.] Clemson Univ, Dept Psychol, Clemson, SC 29634 USA. [Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. RP Grubaugh, AL (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, POB 250861, Charleston, SC 29425 USA. EM grubaugh@musc.edu FU NIDDK NIH HHS [K24 DK093699]; NIMH NIH HHS [K24 MH074468-03, K24 MH074468, K24 MH074468-04, K24 MH074468-05, MH074468] NR 210 TC 62 Z9 64 U1 16 U2 46 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD AUG PY 2011 VL 31 IS 6 BP 883 EP 899 DI 10.1016/j.cpr.2011.04.003 PG 17 WC Psychology, Clinical SC Psychology GA 804TL UT WOS:000293676800001 PM 21596012 ER PT J AU Li, G Biju, KC Xu, X Zhou, Q Chen, C Valente, AJ He, W Reddick, RL Freeman, GL Ahuja, SS Clark, RA Li, S AF Li, G. Biju, K. C. Xu, X. Zhou, Q. Chen, C. Valente, A. J. He, W. Reddick, R. L. Freeman, G. L. Ahuja, S. S. Clark, R. A. Li, S. TI Macrophage LXR alpha gene therapy ameliorates atherosclerosis as well as hypertriglyceridemia in LDLR-/- mice SO GENE THERAPY LA English DT Article DE LXR alpha; stem cell gene therapy; macrophage; atherosclerosis; triglyceride ID LIVER-X-RECEPTORS; DENSITY-LIPOPROTEIN RECEPTOR; APOLIPOPROTEIN-E; DEFICIENT MICE; LESION FORMATION; METABOLISM; EXPRESSION; DISEASE; ATHEROGENESIS; CHOLESTEROL AB Liver X receptors (LXRs) are implicated in the regulation of cholesterol homeostasis, inflammatory response and atherogenesis. Administration of LXR agonists inhibits the progress of atherosclerosis, and also increases plasma triglyceride levels, representing an obstacle to their use in treating this disease. The objective of this study was to develop an alternative approach that could overcome this obstacle. Eight-week-old low-density lipoprotein receptor-deficient (LDLR-/-)mice were transplanted with hematopoietic stem cell (HSC)-enriched bone marrow cells transduced with lentivectors expressing either green fluorescent protein (GFP) (Lenti-SP-GFP, control) or LXR alpha (Lenti-SP-LXR alpha) driven by a synthetic macrophage promoter. At 4 weeks post-transplant, the mice were fed with a Western diet for 8 weeks and then killed. Compared with Lenti-SP-GFP mice, the Lenti-SP-LXR alpha mice had a 30% reduction in atherosclerotic lesions, which was accompanied by increases in levels of macrophage expression of cholesterol efflux genes apolipoprotein E and ATP-binding cassette A1, as well as decreases in plasma inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha. Intriguingly, a 50% reduction of plasma triglyceride level was also observed. We conclude that HSC-based macrophage LXR alpha gene therapy ameliorates the development of atherosclerosis along with an unexpected concomitant reduction of plasma triglyceride levels in LDLR-/- mice. These findings highlight the potential value of macrophage LXR expression as an avenue for therapeutic intervention against atherosclerosis. Gene Therapy (2011) 18, 835-841; doi:10.1038/gt.2011.29; published online 10 March 2011 C1 [Li, G.; Biju, K. C.; Xu, X.; Zhou, Q.; Chen, C.; Valente, A. J.; He, W.; Freeman, G. L.; Ahuja, S. S.; Clark, R. A.; Li, S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Li, G.; Biju, K. C.; Xu, X.; Zhou, Q.; Chen, C.; Valente, A. J.; He, W.; Freeman, G. L.; Ahuja, S. S.; Clark, R. A.; Li, S.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. [Reddick, R. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Reddick, R. L.] S TexasVet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. [Li, S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. RP Li, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM lis1@uthscsa.edu FU Research Division of the Department of Veterans Affairs; Texas Affiliate of the American Heart Association FX We are grateful to Ronald M Evans (The Salk Institute for Biological Studies, San Diego, CA, USA) for providing mouse LXR alpha cDNA (pCMX-mLXR alpha) and Jessica Han for her technical assistance. This study was supported by a research grant from the Research Division of the Department of Veterans Affairs and a Grant-in-Aid from the Texas Affiliate of the American Heart Association. NR 35 TC 10 Z9 11 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD AUG PY 2011 VL 18 IS 8 BP 835 EP 841 DI 10.1038/gt.2011.29 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 806CE UT WOS:000293779500010 PM 21390069 ER PT J AU Ta, NN Schuyler, CA Li, YC Lopes-Virella, MF Huang, Y AF Ta, Nga N. Schuyler, Corinne A. Li, Yanchun Lopes-Virella, Maria F. Huang, Yan TI DPP-4 (CD26) Inhibitor Alogliptin Inhibits Atherosclerosis in Diabetic Apolipoprotein E-Deficient Mice SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE dipeptidyl peptidase-4; CD26; atherosclerosis; diabetes; inflammation ID DIPEPTIDYL-PEPTIDASE-IV; U937 MONONUCLEAR-CELLS; E-KNOCKOUT MICE; DP-IV; EXPRESSION; ACTIVATION; GLUCOSE; LIPOPOLYSACCHARIDE; 17-BETA-ESTRADIOL; INTERLEUKIN-6 AB Dipeptidyl peptidase-4 (DPP-4 or CD26) inhibitors, a new class of antidiabetic compounds, are effective in the treatment of hyperglycemia. Because atherosclerosis-related cardiovascular diseases are the major complications of diabetes, it is important to determine the effect of DPP-4 inhibitors on atherosclerosis. In this study, nondiabetic and diabetic apolipoprotein E-deficient mice were treated with DPP-4 inhibitor alogliptin for 24 weeks, and atherosclerotic lesions in aortic origins were examined. Results showed that diabetes significantly increased atherosclerotic lesions, but alogliptin treatment reduced atherosclerotic lesions in diabetic mice. Metabolic studies showed that diabetes increased plasma glucose and that alogliptin treatment reduced glucose. Furthermore, immunohistochemistry study showed that diabetes increased interleukin-6 (IL-6) and IL-1b protein expression in atherosclerotic plaques, but alogliptin treatment attenuated diabetes-augmented IL-6 and IL-1b expression. In consistence with the observations from the mouse models, our in vitro studies showed that alogliptin-inhibited toll-like receptor 4 (TLR-4)-mediated upregulation of IL-6, IL-1b, and other proinflammatory cytokines by mononuclear cells. Taken together, our findings showed that alogliptin-inhibited atherosclerosis in diabetic apolipoprotein E-deficient mice and that the actions of alogliptin on both glucose and inflammation may contribute to the inhibition. C1 [Schuyler, Corinne A.; Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Dept Res & Dev, Charleston, SC 29403 USA. [Ta, Nga N.; Li, Yanchun; Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Dept Res & Dev, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU Takeda Pharmaceuticals North America, Inc; Department of Veterans Affairs; NIH [DE016353]; Takeda Pharmaceuticals North America, Inc. FX Supported by a preclinical grant from Takeda Pharmaceuticals North America, Inc, a Merit Review grant from Department of Veterans Affairs and NIH grant DE016353 (to Y.H.).; This study was partially funded by a preclinical grant from Takeda Pharmaceuticals North America, Inc. NR 41 TC 72 Z9 78 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD AUG PY 2011 VL 58 IS 2 BP 157 EP 166 DI 10.1097/FJC.0b013e31821e5626 PG 10 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 806AS UT WOS:000293773900007 PM 21558879 ER PT J AU Pistilli, EE Bogdanovich, S Garton, F Yang, N Gulbin, JP Conner, JD Anderson, BG Quinn, LS North, K Ahima, RS Khurana, TS AF Pistilli, Emidio E. Bogdanovich, Sasha Garton, Fleur Yang, Nan Gulbin, Jason P. Conner, Jennifer D. Anderson, Barbara G. Quinn, LeBris S. North, Kathryn Ahima, Rexford S. Khurana, Tejvir S. TI Loss of IL-15 receptor alpha alters the endurance, fatigability, and metabolic characteristics of mouse fast skeletal muscles SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; RETRACTED ARTICLE. SEE; TUMOR-BEARING RATS; INTERLEUKIN-15 RECEPTOR; TRANSCRIPTIONAL COACTIVATOR; CONTRACTILE PROPERTIES; EXTRAOCULAR-MUSCLE; MOTOR UNITS; BETA-CHAIN; IN-VIVO AB IL-15 receptor alpha (IL-15R alpha) is a component of the heterotrimeric plasma membrane receptor for the pleiotropic cytokine IL-15. However, IL-15R alpha is not merely an IL-15 receptor subunit, as mice lacking either IL-15 or IL-15R alpha have unique phenotypes. IL-15 and IL-15R alpha have been implicated in muscle phenotypes, but a role in muscle physiology has not been defined. Here, we have shown that loss of IL-15R alpha. induces a functional oxidative shift in fast muscles, substantially increasing fatigue resistance and exercise capacity. IL-15R alpha-knockout (IL-15R alpha-KO) mice ran greater distances and had greater ambulatory activity than controls. Fast muscles displayed fatigue resistance and a slower contractile phenotype. The molecular signature of these muscles included altered markers of mitochondrial biogenesis and calcium homeostasis. Morphologically, fast muscles had a greater number of muscle fibers, smaller fiber areas, and a greater ratio of nuclei to fiber area. The alterations of physiological properties and increased resistance to fatigue in fast muscles are consistent with a shift toward a slower, more oxidative phenotype. Consistent with a conserved functional role in humans, a genetic association was found between a SNP in the IL15RA gene and endurance in athletes stratified by sport. Therefore, we propose that IL-15R alpha has a role in defining the phenotype of fast skeletal muscles in vivo. C1 [Khurana, Tejvir S.] Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. [Pistilli, Emidio E.; Bogdanovich, Sasha; Khurana, Tejvir S.] Univ Penn, Penn Muscle Inst, Philadelphia, PA 19104 USA. [Garton, Fleur; Yang, Nan; North, Kathryn] Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Sydney, NSW, Australia. [Gulbin, Jason P.] AIS, Canberra, ACT, Australia. [Conner, Jennifer D.; Anderson, Barbara G.; Quinn, LeBris S.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Anderson, Barbara G.; Quinn, LeBris S.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Ahima, Rexford S.] Univ Penn, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. RP Khurana, TS (reprint author), Univ Penn, Sch Med, Dept Physiol, 3700 Hamilton Walk,A601 Richards Bldg, Philadelphia, PA 19104 USA. EM tsk@mail.med.upenn.edu RI Garton, Fleur/H-7713-2016; North, Kathryn/K-6476-2012 OI Garton, Fleur/0000-0002-1490-5930; North, Kathryn/0000-0003-0841-8009 FU NIH under Ruth L. Kirschstein National Research Service from National Institute of Arthritis and Musculoskeletal and Skin Diseases [5T32AR053461, EY013862, AR48871]; [R01AG024136] FX This research was supported by the NIH under Ruth L. Kirschstein National Research Service Award 5T32AR053461 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (to E.E. Pistilli), EY013862 and AR48871 to T.S. Khurana, and R01AG024136 to L.S. Quinn, with resources from the VA Puget Sound Health Care System. The authors acknowledge Ravindra Dhir for collection and analysis of body composition and ambulatory activity data. NR 67 TC 30 Z9 31 U1 0 U2 7 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 AUG PY 2011 VL 121 IS 8 BP 3120 EP 3132 DI 10.1172/JCI44945 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 802FU UT WOS:000293495500023 PM 21765213 ER PT J AU Kim, JS Werth, VP AF Kim, Jessica S. Werth, Victoria P. TI Identification of Specific Chondroitin Sulfate Species in Cutaneous Autoimmune Disease SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE chondroitin sulfate; glycosaminoglycans; lupus erythematosus; dermatomyositis; cutaneous autoimmune disease ID TRABECULAR MESHWORK CELLS; HUMAN SKIN FIBROBLASTS; CD44 SPLICE VARIANTS; ENDOTHELIAL-CELLS; SOLUBLE CD44; TNF-ALPHA; INFLAMMATORY MYOPATHIES; DIFFERENTIAL REGULATION; EXTRACELLULAR-MATRIX; LUPUS-ERYTHEMATOSUS AB Cutaneous lupus erythematosus and dermatomyositis (DM) are chronic inflammatory diseases of the skin with accumulated dermal mucin. Earlier work has shown chondroitin sulfate (CS) accumulation within the dermis of discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and DM lesions compared with control skin. Immunohistochemistry for C4S revealed a greater density in DLE and DM lesions, whereas SCLE lesions did not differ from controls. Scleredema and scleromyxedema are attributed to increased hyaluronic acid, and lesional samples from these diseases also demonstrated accumulated dermal C4S. Interferon-gamma and interleukin-1 alpha, but not interferon-alpha, treatment of cultured dermal fibroblasts induced mRNA expression of CHST-11, which attaches sulfates to the 4-position of unsulfated chondroitin. These studies on possible CS core proteins revealed that serglycin, known to have C6S side chains in endothelial cells, had greater density within DM dermal endothelia but not in DLE or SCLE, following the pattern of C6S overexpression reported previously. CD44 variants expand the CS binding repertoire of the glycoprotein; CD44v7 co-localized to the distribution of C4S in DLE lesions, a finding not observed in DM, SCLE lesions, or controls. Because C4S and C6S have immunologic effects, their dysregulation in cutaneous mucinoses may contribute to the pathogenesis of these disorders. (J Histochem Cytochem 59:780-790, 2011) C1 [Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Kim, Jessica S.] NYU, Sch Med, New York, NY USA. [Kim, Jessica S.; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Werth, VP (reprint author), Univ Penn, Dept Dermatol, 2 Rhoads Pavil,36th & Spruce St, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Lupus Foundation of America; Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development) FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This material is based on work supported by the Lupus Foundation of America and in part by a Merit Review Grant from the Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development). NR 66 TC 7 Z9 7 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD AUG PY 2011 VL 59 IS 8 BP 780 EP 790 DI 10.1369/0022155411411304 PG 11 WC Cell Biology SC Cell Biology GA 805DI UT WOS:000293706200006 PM 21804080 ER PT J AU Eth, S Leong, GB AF Eth, Spencer Leong, Gregory B. TI Psychiatric Ethics Foundational and Evolutionary SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Psychiatric ethics; research ethics; post-9/11 ethics; ethics education ID CLINICAL-RESEARCH; INFORMED-CONSENT; TUSKEGEE; MEDICINE; LESSONS; ISSUES; DUTY AB As with the basic and clinical sciences, the field of medical ethics, in particular, that of psychiatric ethics, has grown and developed during the last four decades, the time when Dr. Eugene Brody edited the Journal of Nervous and Mental Disease. In this paper, the authors will consider a series of ethical problems that psychiatrists have identified in their clinical practice and suggest paths to resolution that may artfully balance conflicts in core moral beliefs. C1 [Eth, Spencer] VA Med Ctr, Psychiat Serv, Miami, FL USA. [Eth, Spencer] Univ Miami, Miller Sch Med, Dept Psychiat, Miami, FL 33136 USA. [Leong, Gregory B.] VA Puget Sound Hlth Care Syst, Amer Lake Div, Mental Hlth Serv, Tacoma, WA USA. [Leong, Gregory B.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Eth, S (reprint author), VA Med Ctr, Psychiat Serv, Miami, FL USA. NR 33 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD AUG PY 2011 VL 199 IS 8 BP 562 EP 566 DI 10.1097/NMD.0b013e318225f0fe PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 802IE UT WOS:000293502000009 PM 21814079 ER PT J AU Kerlikowske, K Phipps, AI AF Kerlikowske, Karla Phipps, Amanda I. TI Breast Density Influences Tumor Subtypes and Tumor Aggressiveness SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ESTROGEN-RECEPTOR STATUS; AFRICAN-AMERICAN WOMEN; MAMMOGRAPHIC DENSITY; CANCER RISK; POSTMENOPAUSAL WOMEN; HORMONE-RECEPTOR; ASSOCIATION; SURVIVAL; FEATURES; DIFFERENCE C1 [Kerlikowske, Karla] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, Dept Vet Affairs, San Francisco, CA 94121 USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Epidemiol & Biostat, Dept Med, San Francisco, CA 94121 USA. [Phipps, Amanda I.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Phipps, Amanda I.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP Kerlikowske, K (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, Dept Vet Affairs, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM karla.kerlikowske@ucsf.edu FU NCI NIH HHS [P01 CA107584, R25 CA94880]; PHS HHS [P50 C A58207] NR 41 TC 7 Z9 7 U1 0 U2 3 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 AUG PY 2011 VL 103 IS 15 BP 1143 EP 1145 DI 10.1093/jnci/djr263 PG 3 WC Oncology SC Oncology GA 804BH UT WOS:000293628200003 PM 21795663 ER PT J AU Norvell, DC Turner, AP Williams, RM Hakimi, KN Czerniecki, JM AF Norvell, Daniel C. Turner, Aaron P. Williams, Rhonda M. Hakimi, Kevin N. Czerniecki, Joseph M. TI Defining successful mobility after lower extremity amputation for complications of peripheral vascular disease and diabetes SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID LOWER-LIMB AMPUTATION; QUALITY-OF-LIFE; WALKING ABILITY; UNITED-STATES; AMPUTEES; REHABILITATION; SATISFACTION; CAPABILITIES; POPULATION; VALIDATION AB Background: Information about longer-term functional outcomes following lower extremity amputation for peripheral vascular disease and diabetes remains limited. This study examined factors associated with mobility success during the first year following amputation. Methods: Prospective cohort study of 87 amputees experiencing a first major unilateral amputation surgery. Seventy-five (86%) participants completed 12-month follow-up interview. Results: Twenty-eight subjects (37%) achieved mobility success, defined as returning to or exceeding a baseline level of mobility on the locomotor capability index (LCI-5). Forty-three subjects (57%) were satisfied with their mobility. Individuals who were 65 years of age and older (risk difference [RD] = -0.52; 95% confidence interval [CI]: -0.75, -0.29), reported a current alcohol use disorder (RI) = -0.37; 95% CI: -0.48, -0.26), had a history of hypertension (RD = -0.23; 95% CI: -0.43, -0.03) or treatment for anxiety or depression (RD = -0.39; 95% CI: -0.50, -0.28) were less likely to achieve mobility success. Mobility success was associated with mobility satisfaction (RD = 0.36; 95% CI: 0.20, 0.53) and satisfaction with life (RD = 0.28; 95% CI: 0.06, 0.50). Although higher absolute mobility at 12 months was also associated with mobility satisfaction and overall life satisfaction, 50% of individuals who achieved success with low to moderate 12-month mobility function reported they were satisfied with their mobility. Conclusion: Defining success after amputation in relation to an individual's specific mobility prior to the development of limb impairment which led to amputation provides a useful, patient-centered measure that takes other aspects of health, function, and impairment into account. (J Vase Surg 2011;54:412-9.) C1 [Turner, Aaron P.] VA Puget Sound Hlth Care Syst, Dept Rehabil Med, Seattle, WA 98108 USA. [Norvell, Daniel C.] Spectrum Res Inc, Tacoma, WA USA. [Turner, Aaron P.; Williams, Rhonda M.; Hakimi, Kevin N.; Czerniecki, Joseph M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Dept Rehabil Med, S-117-RCS,1660 S Columbian Way, Seattle, WA 98108 USA. EM aaron.Turner@va.gov OI Turner, Aaron/0000-0001-6897-8003 FU US Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development [A41241, B4927W] FX Supported by the US Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development (Merit Review A41241 Joseph Czerniecki, PI, and Career Development Award B4927W Aaron Turner, PI). NR 29 TC 24 Z9 24 U1 1 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD AUG PY 2011 VL 54 IS 2 BP 412 EP 419 DI 10.1016/j.jvs.2011.01.046 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 806NH UT WOS:000293814400023 PM 21531528 ER PT J AU Chen, HT Kougias, P Lin, PH Bechara, CF AF Chen, Huiting Kougias, Panagiotis Lin, Peter H. Bechara, Carlos F. TI Jaw claudication in the era of carotid stenting SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID INTERMITTENT CLAUDICATION; ARTERY; ENDARTERECTOMY; OCCLUSION; DISEASE; PAIN AB Jaw claudication could result from external carotid artery (ECA) occlusive disease. Carotid artery stenting (CAS) has been shown to worsen the disease in the ECA. This could potentially worsen the symptoms in patients with pre-existing jaw claudication undergoing CAS. Meanwhile, ECA endarterectomy is routinely done during internal carotid artery endarterectomy (CEA). This has been shown to alleviate jaw claudication symptoms. We report a case of a high-risk patient for CEA who presented with symptomatic carotid disease as well as bilateral jaw claudication. Both symptoms resolved after CEA. We also present the case of another patient treated for recurrent high-grade carotid disease with CAS resulting in acute ECA occlusion and jaw claudication. High-risk patients with symptomatic carotid disease and jaw claudication should be considered for CEA and not only CAS. (J Vase Surg 2011;54:526-8.) C1 [Chen, Huiting; Kougias, Panagiotis; Lin, Peter H.; Bechara, Carlos F.] Baylor Coll Med, Michael E DeBakey Dept Surg, Michael E DeBakey Vet Adm Med Ctr, Div Vasc & Endovasc Therapy, Houston, TX 77030 USA. RP Bechara, CF (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Michael E DeBakey VA Med Ctr, Div Vasc Surg & Endovasc Therapy, 2002 Holcombe Blvd 112, Houston, TX 77030 USA. EM bechara@bcm.edu NR 14 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD AUG PY 2011 VL 54 IS 2 BP 526 EP 528 DI 10.1016/j.jvs.2010.12.057 PG 3 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 806NH UT WOS:000293814400044 PM 21397442 ER PT J AU Sano, M Bell, KL Galasko, D Galvin, JE Thomas, RG van Dyck, CH Aisen, PS AF Sano, M. Bell, K. L. Galasko, D. Galvin, J. E. Thomas, R. G. van Dyck, C. H. Aisen, P. S. TI A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease SO NEUROLOGY LA English DT Article ID C-REACTIVE PROTEIN; CLINICAL-TRIALS; COGNITIVE FUNCTION; MOUSE MODEL; STATINS; RISK; DEMENTIA; HEALTH; IMMUNOREACTIVITY; ATORVASTATIN AB Background: Lowering cholesterol is associated with reduced CNS amyloid deposition and increased dietary cholesterol increases amyloid accumulation in animal studies. Epidemiologic data suggest that use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may decrease the risk of Alzheimer disease (AD) and a single-site trial suggested possible benefit in cognition with statin treatment in AD, supporting the hypothesis that statin therapy is useful in the treatment of AD. Objective: To determine if the lipid-lowering agent simvastatin slows the progression of symptoms in AD. Methods: This randomized, double-blind, placebo-controlled trial of simvastatin was conducted in individuals with mild to moderate AD and normal lipid levels. Participants were randomly assigned to receive simvastatin, 20 mg/day, for 6 weeks then 40 mg per day for the remainder of 18 months or identical placebo. The primary outcome was the rate of change in the Alzheimer's Disease Assessment Scale-cognitive portion (ADAS-Cog). Secondary outcomes measured clinical global change, cognition, function, and behavior. Results: A total of 406 individuals were randomized: 204 to simvastatin and 202 to placebo. Simvastatin lowered lipid levels but had no effect on change in ADAS-Cog score or the secondary outcome measures. There was no evidence of increased adverse events with simvastatin treatment. Conclusion: Simvastatin had no benefit on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol. Classification of evidence: This study provides Class I evidence that simvastatin 40 mg/day does not slow decline on the ADAS-Cog. Neurology (R) 2011;77:556-563 C1 [Sano, M.] Mt Sinai Sch Med, New York, NY USA. [Sano, M.] James J Peters VAMC, Bronx, NY 10468 USA. [Bell, K. L.] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Galasko, D.; Aisen, P. S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Galvin, J. E.] NYU, Langone Med Ctr, Ctr Excellence Brain Aging, New York, NY USA. [Galvin, J. E.] NYU, Langone Med Ctr, Alzheimer Dis Ctr, New York, NY USA. [Thomas, R. G.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [van Dyck, C. H.] Yale Univ, Sch Med, Alzheimers Dis Res Unit, New Haven, CT USA. RP Sano, M (reprint author), Mt Sinai Sch Med, 130 W Kingsbridge Rd,Code 150,Rm 1F01, Bronx, NY 10468 USA. EM mary.sano@mssm.edu FU NIH (NIA/NCRR); Baxter International Inc.; Wyeth; Pfizer Inc; Janssen Alzheimer Immunotherapy Research & Development, LLC; NIH/NIA; Eli Lilly and Company; Avid Radiopharmaceuticals, Inc.; Novartis; Elan Corporation; Bristol-Myers Squibb; Alzheimer Association; US Department of Defense; Medivation, Inc.; Bayer Schering Pharma; Abbott; GlaxoSmithKline; Myriad Genetics, Inc.; Neurochem Inc; Sanofi-Synthelabo Research; Janssen; Eisai Inc.; Merck Serono; Mitsubishi Tanabe Pharma Corporation; NIH (NIA, NIMH); Alzheimer's Association; American Health Assistance Foundation; National Alliance for Research on Schizophrenia and Affective Disorders (NARSAD); Shire plc; NIH (NIA, NINDS); Kavli Neuroscience Institute at Yale; Merck; NIA [U01AG10483]; Forest Laboratories, Inc. FX This work was supported by NIA grant U01AG10483. The ADCS received an unrestricted educational grant from Merck who also supplied drug and placebo. Merck did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation of the manuscript. Authors had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.; Dr. Sano serves on a scientific advisory board for Medivation, Inc.; serves as a consultant for Bayer Schering Pharma, Bristol-Meyers Squibb, Elan Corporation, Genentech, Inc., Medivation, Inc., Medpace Inc., Pfizer Inc, Janssen, Takeda Pharmaceutical Company Limited, and United Biosource Corporation; and receives research support from the NIH (NIA/NCRR). Dr. Bell serves on speakers' bureaus for and has received speaker honoraria from Eisai Inc. and Forest Laboratories, Inc.; and receives research support from Baxter International Inc., Wyeth, Pfizer Inc, Janssen Alzheimer Immunotherapy Research & Development, LLC, and the NIH/NIA. Dr. Galasko serves on a scientific advisory board for Janssen/Elan Corporation; serves as Co-Editor for Alzheimer's Research and Therapy; serves as a consultant for United BioSource Corporation; and receives research support from Eli Lilly and Company, Avid Radiopharmaceuticals, Inc., and the NIH/NIA. Dr. Galvin serves on a scientific advisory board for the American Federation for Aging Research and on the Board of Directors and the Scientific Advisory Council for the Lewy Body Dementia Association; serves on the editorial boards of Alzheimer's Disease and Associated Disorders and Acta Neuropathologica; serves on speakers' bureaus for Pfizer Inc, Eisai Inc., Novartis, and Forest Laboratories, Inc.; has served as a consultant for Novartis, Forest Laboratories, Inc., Pfizer Inc, Eisai Inc., Janssen, and Medivation, Inc.; has received license fee payments for AD8 dementia screening test (copyrighted): license agreements between Washington University and Pfizer Inc, Eisai Inc., and Novartis; and receives research support from Novartis, Eli Lilly and Company, Elan Corporation, Wyeth, Bristol-Myers Squibb, the NIH/NIA, and the Alzheimer Association. Dr. Thomas has served on a scientific advisory board for Myriad Genetics, Inc.; has served as a consultant for Medivation, Inc., Myriad Genetics, Inc., Bristol-Meyers Squibb, and Neurochem Inc.; and receives research support from the US Department of Defense and the NIH/NIA. Dr. van Dyck has served on scientific advisory boards for Elan Corporation, Pfizer Inc, GlaxoSmithKline, Bristol-Myers Squibb, and Forest Laboratories, Inc.; has received funding for travel and speaker honoraria from Forest Laboratories, Inc.; his spouse owns or has applied for patents re: Use of guanfacine in the treatment of behavioral disorders, Use of lofexidine in the treatment of behavioral disorders, Chelerythrine, analogs thereof and their use in the treatment of bipolar disorder and other cognitive disorders (formerly licensed to Marinus Pharmaceuticals, Inc.); his spouse receives publishing royalties for The Neuropharmacology of Stimulant Drugs: Implications for AD/HD (Oxford University Press, 2000); serves as a consultant for Elan Corporation, Pfizer Inc, GlaxoSmithKline, Bristol-Myers Squibb, Forest Laboratories, Inc., and Merck Serono, and his spouse serves as a consultant for Shire plc; served on the speakers' bureau for Forest Laboratories, Inc.; receives/has received research support from Wyeth, Eli Lilly and Company, Pfizer Inc, Bristol-Myers Squibb, Medivation, Inc., Bayer Schering Pharma, Abbott, Elan Corporation, GlaxoSmithKline, Myriad Genetics, Inc., Neurochem Inc, Sanofi-Synthelabo Research, Janssen, Eisai Inc.; , Merck Serono, Mitsubishi Tanabe Pharma Corporation, the NIH (NIA, NIMH), Alzheimer's Association, American Health Assistance Foundation, and the National Alliance for Research on Schizophrenia and Affective Disorders (NARSAD); his spouse receives research support fro Shire plc, the NIH (NIA, NINDS), the Kavli Neuroscience Institute at Yale, and NARSAD; and his spouse has received license fee payments and receives royalties from Shire plc for a patent re: Use of guanfacine in the treatment of behavioral disorders. Dr. Aisen serves on a scientific advisory board for NeuroPhage and Novartis; serves on the editorial boards of BMC Medicine and Alzheimer's Research & Therapy; is listed as inventor on a patent re: DHA therapy for apolipoprotein E4 negative Alzheimer's disease (potential royalties assigned in full to UCSD); serves as a consultant to Elan Corporation, Wyeth, Eisai Inc., Schering-Plough Corp., Bristol-Myers Squibb, Eli Lilly and Company, NeuroPhage, Merck & Co., Roche, Amgen, Genentech, Inc., Abbott, Pfizer Inc, Novartis, Bayer Schering Pharma, Astellas Pharma Inc., Dainippon Sumitomo Pharma, BioMarin Pharmaceutical Inc., Solvay Pharmaceuticals, Inc., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo, AstraZeneca, Janssen, and Medivation, Inc.; receives research support from Pfizer Inc, Bayer Schering Pharma, Baxter International Inc., and the NIH/NIA; and has received stock options from Medivation, Inc. and NeuroPhage. NR 38 TC 106 Z9 111 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 2011 VL 77 IS 6 BP 556 EP 563 DI 10.1212/WNL.0b013e318228bf11 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 804MW UT WOS:000293658900011 PM 21795660 ER PT J AU Eiseman, B AF Eiseman, Ben TI SUS Lifetime Achievement Award Lecture The elder surgeon's role in academia SO SURGERY LA Latin DT Editorial Material C1 Denver VA Med Ctr, Denver, CO 80220 USA. RP Eiseman, B (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM ben.eiseman@va.gov NR 12 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 2011 VL 150 IS 2 BP 141 EP 145 DI 10.1016/j.surg.2011.05.002 PG 5 WC Surgery SC Surgery GA 806KI UT WOS:000293805900001 PM 21723577 ER PT J AU Anger, JT Scott, VCS Sevilla, C Wang, MM Yano, EM AF Anger, Jennifer T. Scott, Victoria C. S. Sevilla, Claudia Wang, Mingming Yano, Elizabeth M. TI Patterns of Management of Urethral Stricture Disease in the Veterans Affairs System SO UROLOGY LA English DT Article ID TERM-FOLLOW-UP; INTERNAL URETHROTOMY; HEALTH-CARE; URETHROPLASTY; DILATION; ANASTOMOSIS; GRAFT AB OBJECTIVES To describe the number of urethral dilations, urethrotomies, and urethroplasties performed on men with a diagnosis of urethral stricture disease seeking care in the Veterans Affairs (VA) health care system in southern California and southern Nevada over a 5-year period. To date, few health services research studies have evaluated patterns of care for urethral stricture disease using national datasets. METHODS We analyzed stricture treatment for male veterans with an ICD-9 diagnosis code for urethral stricture in the National Patient Care Database (NPCD). Encounters for urethral stricture procedures performed were identified based on the presence of Physicians Current Procedural Terminology Coding System (4th edition, CPT-4) codes for treatments performed during the fiscal years 2002-2006. RESULTS A total of 1457 men carried a diagnosis of urethral stricture disease during the index time period. Of these, 333 men (23%) underwent 431 procedures. Of the 216 men who underwent urethral dilations, 170 (79%) underwent only 1 procedure and 26 (12%) underwent 2 procedures. Of the 79 men who underwent urethrotomy, 76 (96%) underwent 1 procedure. Sixteen men (5%) underwent a urethroplasty, 8 of whom underwent a perineal urethrostomy. CONCLUSIONS The vast majority of men treated for stricture disease underwent only 1 such procedure over a 5-year time period. Further research is required to investigate whether this is a quality-of-care issue or patients refusing intervention. It is possible that some patients may be temporized for a significant period with dilation/urethrotomy, whereas those with rapid recurrence require early urethroplasty. UROLOGY 78: 454-458, 2011. (C) 2011 Published by Elsevier Inc. C1 Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. Cedars Sinai Med Ctr, Dept Surg, Div Urol, Los Angeles, CA 90048 USA. VA Greater Los Angeles Healthcare Syst, Vet Affairs Hlth Serv Res & Dev Ctr Excellence St, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA. RP Anger, JT (reprint author), 99 La Cienega Blvd,Suite 307, Beverly Hills, CA 90211 USA. EM angerj@cshs.org FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (HSRD) [65-106]; VA Greater Lost Angeles HSR&D Center of Excellence for the Study of Healthcare Provider Behavior FX This material was based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (HSR&D) Service through a Locally Initiated Project (Project # 65-106) funded by the VA Greater Lost Angeles HSR&D Center of Excellence for the Study of Healthcare Provider Behavior. NR 20 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD AUG PY 2011 VL 78 IS 2 BP 454 EP 458 DI 10.1016/j.urology.2010.12.081 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 803JH UT WOS:000293577100064 PM 21689845 ER PT J AU Sher, L AF Sher, Leo TI Brain-derived neurotrophic factor and suicidal behavior in adolescents SO WORLD JOURNAL OF PEDIATRICS LA English DT Editorial Material ID RISK-FACTORS; BDNF; CHILDREN C1 [Sher, Leo] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, Dept Psychiat, New York, NY USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM drleosher@gmail.com NR 18 TC 1 Z9 3 U1 1 U2 2 PU ZHEJIANG UNIV SCH MEDICINE PI HANGZHOU PA CHILDRENS HOSPITAL, 57 ZHUGAN XIANG, HANGZHOU, 310003, PEOPLES R CHINA SN 1708-8569 J9 WORLD J PEDIATR JI World Journal of Pediatrics PD AUG PY 2011 VL 7 IS 3 BP 197 EP 198 DI 10.1007/s12519-011-0316-2 PG 2 WC Pediatrics SC Pediatrics GA 804FX UT WOS:000293640800001 PM 21822986 ER PT J AU Vigen, CLP Mack, WJ Keefe, RSE Sano, M Sultzer, DL Stroup, TS Dagerman, KS Hsiao, JK Lebowitz, BD Lyketsos, CG Tariot, PN Zheng, L Schneider, LS AF Vigen, Cheryl L. P. Mack, Wendy J. Keefe, Richard S. E. Sano, Mary Sultzer, David L. Stroup, T. Scott Dagerman, Karen S. Hsiao, John K. Lebowitz, Barry D. Lyketsos, Constantine G. Tariot, Pierre N. Zheng, Ling Schneider, Lon S. TI Cognitive Effects of Atypical Antipsychotic Medications in Patients With Alzheimer's Disease: Outcomes From CATIE-AD SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID RATING-SCALE BPRS; DEMENTIA; SCHIZOPHRENIA; TRIAL; METAANALYSIS; OLANZAPINE; QUETIAPINE; SYMPTOMS; DRUGS; RISPERIDONE AB Objective: The impact of the atypical antipsychotics olanzapine, quetiapine, and risperidone on cognition in patients with Alzheimer's disease is unclear. The authors assessed the effects of time and treatment on neuropsychological functioning during the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study (CATIE-AD). Method: CATIE-AD included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior who were randomly assigned to receive masked, flexible-dose olanzapine, quetiapine, risperidone, or placebo. Based on their clinicians' judgment, patients could discontinue the originally assigned medication and receive another randomly assigned medication. Patients were followed for 36 weeks, and cognitive assessments were obtained at baseline and at 12, 24, and 36 weeks. Outcomes were compared for 357 patients for whom data were available for at least one cognitive measure at baseline and one follow-up assessment that took place after they had been on their prescribed medication or placebo for at least 2 weeks. Results: Overall, patients showed steady, significant declines over time in most cognitive areas, including in scores on the Mini-Mental State Examination (MMSE; -2.4 points over 36 weeks) and the cognitive subscale of the Alzheimer's Disease Assessment Scale (-4.4 points). Cognitive function declined more in patients receiving antipsychotics than in those given placebo on multiple cognitive measures, including the MMSE, the cognitive subscale of the Brief Psychiatric Rating Scale, and a cognitive summary score summarizing change on 18 cognitive tests. Conclusions: In CATIE-AD, atypical antipsychotics were associated with worsening cognitive function at a magnitude consistent with 1 year's deterioration compared with placebo. Further cognitive impairment is an additional risk of treatment with atypical antipsychotics that should be considered when treating patients with Alzheimer's disease. C1 [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Gerontol, Los Angeles, CA 90033 USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Columbia Univ, Dept Psychiat, Sch Med, New York, NY USA. Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Banner Hlth Ctr, Phoenix, AZ USA. Univ Calif San Diego, VA Greater Los Angeles Healthcare Syst, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Schneider, LS (reprint author), Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, 1510 San Pablo St,HCC 600, Los Angeles, CA 90033 USA. EM lschneid@usc.edu RI Stroup, Thomas/F-9188-2014 OI Stroup, Thomas/0000-0002-3123-0672 FU AstraZeneca; Eli Lilly; Forest; Pfizer; Ad-lyfe; Associated Jewish Federation of Baltimore; Bristol-Myers Squibb; Eisai; GlaxoSmithKline; Ortho-McNeil; Monitor; Novartis; National Institute on Aging; Supernus; Takeda; Wyeth; Abbott; AC Immune; Alzheimer's Association; Arizona Department of Health Services; Avid; Baxter Healthcare; Elan; Epix; Institute for Mental Health Research; Lundbeck; Memory; Merck; Merz; Mitsubishi Pharma; Myriad; Neurochem; Ono; Sanofi-Aventis; Janssen; NIMH [N01 MH-9001]; USC Alzheimer's Disease Research Center NIH [P50 AG05142]; Department of Veterans Affairs FX Dr. Schneider has been a consultant for Pfizer, Eli Lilly, Johnson & Johnson, AstraZeneca, and Bristol-Myers Squibb. Dr. Keefe has received research support from AstraZeneca, Eli Lilly, and NIMH and has served as a consultant, adviser, or speaker for Abbott, Acadia, BiolineRx, Bristol-Myers Squibb, Cephalon, Cortex, Dainippon Sumitomo Pharma, Eli Lilly, Johnson & Johnson, Lundbeck, Memory Pharmaceuticals, Merck, Orexigen, Organon, Pfizer, Sanofi/Aventis, Schering-Plough, Wyeth, and Xenoport. Dr. Sano has served as a consultant or adviser for Aventis, Bayer, Bristol-Myers Squibb, Eisai, Elan, Forest, Genentech, GlaxoSmithKline, Janssen, Martek, Medivation, Novartis, Ortho-McNeil, Pfizer, Takeda, United BioSource, and Voyager. Dr. Sultzer has received research funding or lecture honoraria from or served as a consultant to AstraZeneca, Eli Lilly, Forest, and Pfizer. Dr. Lyketsos has received research funding, lecture honoraria, or travel support from or served as a consultant or adviser to Ad-lyfe, Associated Jewish Federation of Baltimore, AstraZeneca, Bristol-Myers Squibb, Eisai, Eli Lilly, Forest, GlaxoSmithKline, Ortho-McNeil, Monitor, Novartis, NIMH, National Institute on Aging, Pfizer, Supernus, Takeda, and Wyeth. Dr. Tariot has received research support or consulting or educational fees from Abbott, AC Immune, Alzheimer's Association, Arizona Department of Health Services, AstraZeneca, Avid, Baxter Healthcare, Eisai, Elan, Epix, Forest, GlaxoSmithKline, Institute for Mental Health Research, Lundbeck, Memory, Merck, Merz, Mitsubishi Pharma, Myriad, National Institute on Aging, Neurochem, NIMH, Ono, Pfizer, Sanofi-Aventis, Takeda, and Wyeth; he is also a contributor to the patent "Biomarkers of Alzheimer's Disease." Dr. Stroup has received speaking or consulting fees from Eli Lilly, Janssen, and Lundbeck. The other authors report no financial relationships with commercial interests.; Supported in part by NIMH research contract N01 MH-9001, USC Alzheimer's Disease Research Center NIH P50 AG05142, and the Department of Veterans Affairs. Medications for this study were provided by AstraZeneca, Forest, Janssen, and Eli Lilly. NR 32 TC 85 Z9 86 U1 8 U2 24 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 AUG PY 2011 VL 168 IS 8 BP 831 EP 839 DI 10.1176/appi.ajp.2011.08121844 PG 9 WC Psychiatry SC Psychiatry GA 800SQ UT WOS:000293387600014 PM 21572163 ER PT J AU Kanal, KM Chung, JH Wang, J Bhargava, P Kohr, JR Shuman, WP Stewart, BK AF Kanal, Kalpana M. Chung, Jonathan H. Wang, Jin Bhargava, Puneet Kohr, Jennifer R. Shuman, William P. Stewart, Brent K. TI Image Noise and Liver Lesion Detection With MDCT: A Phantom Study SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE automatic tube current modulation; liver phantom; low-contrast lesion detection; MDCT; noise index ID PHASE HELICAL CT; HEPATOCELLULAR-CARCINOMA; REDUCTION FILTERS; CONTRAST MATERIAL; ABDOMEN AB OBJECTIVE. The purpose of this study was to determine the upper limit of noise for detection of small low-contrast lesions in a liver phantom. MATERIALS AND METHODS. A CT liver phantom containing 21 low-contrast, low-attenuation, circular simulated lesions ranging in size from 2.4 to 10 mm was scanned 23 times at different tube current ranges (varying noise index) on a 64-MDCT scanner with automatic tube current modulation. The attenuation of the simulated lesions was 20 HU less than that of the liver-equivalent background. Three radiologists independently reviewed the resultant CT images, which contained either a low-contrast lesion or no lesion and scored certainty of lesion detection using a 4-point Likert scale. Overall performance was evaluated by sensitivity analysis with receiver operator curve and area under the curve (A(z)) computation for ranges of noise index. RESULTS. The reviewers achieved 100% sensitivity with a noise index of 15 or less for lesions measuring 6.3-10.0 mm (A(z) = 0.96). Increasing noise index to the 17-21 range resulted in a minor decrease in sensitivity and overall performance (sensitivity, 92.3%; A(z) = 0.93). A further increase in noise index to the 23-27 range resulted in a moderate decrease in sensitivity (sensitivity, 81.4%; A(z) = 0.77). Beyond the noise index 23-27 range, sensitivity dropped markedly from 81.4% to 39%. Agreement between the three readers in assessing the image sets was moderate. CONCLUSION. For detection of small low-contrast lesions in the liver phantom model used in this study, the upper limit of noise index may be in the 15-21 range for sensitivity greater than 90%. C1 [Kanal, Kalpana M.; Bhargava, Puneet] Univ Washington, Dept Radiol, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Wang, Jin] Univ Washington, Dept Surg, Seattle, WA 98195 USA. RP Kanal, KM (reprint author), Univ Washington, Dept Radiol, VA Puget Sound Hlth Care Syst, Box 357987,1959 NE Pacific St, Seattle, WA 98195 USA. EM kkanal@u.washington.edu RI Bhargava, Puneet /F-1330-2011 OI Bhargava, Puneet/0000-0002-3849-9666 FU GE Healthcare FX K. M. Kanal has received an honorarium from GE Healthcare for participation in a symposium. W. P. Shuman has received a research grant from GE Healthcare. NR 11 TC 8 Z9 8 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2011 VL 197 IS 2 BP 437 EP 441 DI 10.2214/AJR.10.5726 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 796OY UT WOS:000293062600052 PM 21785091 ER PT J AU Baylor, C Hula, W Donovan, NJ Doyle, PJ Kendall, D Yorkston, K AF Baylor, Carolyn Hula, William Donovan, Neila J. Doyle, Patrick J. Kendall, Diane Yorkston, Kathryn TI An Introduction to Item Response Theory and Rasch Models for Speech-Language Pathologists SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE item response theory; outcomes measurement; Rasch model ID COMMUNICATIVE EFFECTIVENESS SURVEY; PATIENT-REPORTED OUTCOMES; CONSTRUCT-VALIDITY; HEALTH OUTCOMES; REHABILITATION; RELIABILITY; PERFORMANCE; DEPENDENCE; RECOVERY; MULTILOG AB Purpose: To present a primarily conceptual introduction to item response theory (IRT) and Rasch models for speech-language pathologists (SLPs). Method: This tutorial introduces SLPs to basic concepts and terminology related to IRT as well as the most common IRT models. The article then continues with an overview of how instruments are developed using IRT and some basic principles of adaptive testing. Conclusion: IRT is a set of statistical methods that are increasingly used for developing instruments in speech-language pathology. While IRT is not new, its application in speech-language pathology to date has been relatively limited in scope. Several new IRT-based instruments are currently emerging. IRT differs from traditional methods for test development, typically referred to as classical test theory (CTT), in several theoretical and practical ways. Administration, scoring, and interpretation of IRT instruments are different from methods used for most traditional CTT instruments. SLPs will need to understand the basic concepts of IRT instruments to use these tools in their clinical and research work. This article provides an introduction to IRT concepts drawing on examples from speech-language pathology. C1 [Baylor, Carolyn; Kendall, Diane; Yorkston, Kathryn] Univ Washington, Seattle, WA 98195 USA. [Hula, William; Doyle, Patrick J.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Hula, William; Doyle, Patrick J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Donovan, Neila J.] Louisiana State Univ, Baton Rouge, LA 70803 USA. [Kendall, Diane] VA Puget Sound Med Ctr, Seattle, WA USA. RP Baylor, C (reprint author), Univ Washington, Seattle, WA 98195 USA. EM cbaylor@u.washington.edu FU NIDCD NIH HHS [1R03DC010044] NR 60 TC 20 Z9 20 U1 0 U2 5 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 AUG 1 PY 2011 VL 20 IS 3 BP 243 EP 259 DI 10.1044/1058-0360(2011/10-0079) PG 17 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 800RI UT WOS:000293382000008 PM 21622595 ER PT J AU Ben-Menachem, T Dominitz, JA AF Ben-Menachem, Tamir Dominitz, Jason A. TI Acute Upper Gastrointestinal Hemorrhage in an Elderly Woman Taking Aspirin and Clopidogrel SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID ACUTE CORONARY SYNDROMES; ANTIPLATELET THERAPY; MYOCARDIAL-INFARCTION; MANAGEMENT; ULCERS; TRIAL; BLIND; RISK C1 [Ben-Menachem, Tamir] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Dominitz, Jason A.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Ben-Menachem, T (reprint author), Summit Med Grp, 1 Diamond Hill Rd, Berkeley Hts, NJ 07922 USA. EM tbenmenachem@smgnj.com OI Dominitz, Jason/0000-0002-8070-7086 NR 17 TC 0 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 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD AUG PY 2011 VL 9 IS 8 BP 649 EP 652 DI 10.1016/j.cgh.2011.03.022 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 803OW UT WOS:000293591600011 PM 21440673 ER PT J AU Urayama, A Morales, R Niehoff, ML Banks, WA Soto, C AF Urayama, Akihiko Morales, Rodrigo Niehoff, Michael L. Banks, William A. Soto, Claudio TI Initial fate of prions upon peripheral infection: half-life, distribution, clearance, and tissue uptake SO FASEB JOURNAL LA English DT Article DE PrP(Sc); pharmacokinetics; blood-brain barrier ID BLOOD-BRAIN-BARRIER; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; MISFOLDING CYCLIC AMPLIFICATION; MANNOSE 6-PHOSPHATE RECEPTOR; IN-VITRO; PRESYMPTOMATIC DETECTION; SCRAPIE INFECTIVITY; MEDIATED TRANSPORT; LYSOSOMAL-ENZYME; AMYLOID-BETA AB Prion diseases are infectious neurodegenerative disorders associated with the misfolded prion protein (PrP(Sc)), which appears to be the sole component of the infectious agent (termed prion). To produce disease, prions have to be absorbed into the body and reach sufficient quantities in the brain. Very little is known about the biological mechanisms controlling the initial fate of prions. Here, we studied the systemic pharmacokinetics and biodistribution of PrP(Sc) in vivo. After an intravenous injection of highly purified radiolabeled or native unlabeled PrP(Sc), the protein was eliminated rapidly from the serum (half-life of 3.24 h), mostly through tissue uptake. The quantity of intact PrP(Sc) reaching the brain was similar to 0.2% of the injected dose per gram of brain tissue (ID/g). The highest levels were found in liver (similar to 20% ID/g), spleen (similar to 13% ID/g), and kidney (similar to 7.4% ID/g). Cell surface PrP(C) does not appear to play a role in PrP(Sc) pharmacokinetics, since the infectious protein distributed similarly in wild-type and PrP-null mice. To measure tissue uptake kinetics and biodistribution accurately, vascular space in tissues was measured with radioactively labeled albumin coinjected with radioactively labeled PrP(Sc). Our results provide a fundamental pharmacokinetic characterization of PrP(Sc) in vivo, which may be relevant to estimate tissue risks and mechanisms of prion neuroinvasion and to identify novel therapeutic strategies.-Urayama, A., Morales, R., Niehoff, M. L., Banks, W. A., Soto, C. Initial fate of prions upon peripheral infection: half-life, distribution, clearance, and tissue uptake FASEB J. 25, 2792-2803 (2011). www.fasebj.org C1 [Urayama, Akihiko; Morales, Rodrigo; Soto, Claudio] Univ Texas Houston, Med Sch Houston, Dept Neurol, Mitchell Ctr Alzheimers Dis & Related Brain Disor, Houston, TX 77030 USA. [Niehoff, Michael L.] Vet Affairs Med Ctr St Louis, GRECC, St Louis, MO USA. [Niehoff, Michael L.] St Louis Univ, Sch Med, Dept Internal Med, Div Geriatr, St Louis, MO USA. [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. [Banks, William A.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Urayama, A (reprint author), Univ Texas Houston, Med Sch Houston, Dept Neurol, Mitchell Ctr Alzheimers Dis & Related Brain Disor, MSE R468,6431 Fannin St, Houston, TX 77030 USA. EM akihiko.urayama@uth.tmc.edu; claudio.soto@uth.tmc.edu FU U.S. National Institutes of Health [R01 NS050547, P01 AI77774] FX This study was supported by U.S. National Institutes of Health grant R01 NS050547 (to W.A.B. and C.S.) and P01 AI77774 (to C.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. A.U. designed the study, performed the bulk of the experiments, analyzed all data, wrote the manuscript, and managed the peer review process. R.M.L. helped on the characterization of iodinated PrPSc. M.L.N. contributed to HPLC analysis. W.A.B. analyzed all data and critically reviewed the manuscript. C.S. developed the hypothesis, wrote the manuscript, and supervised the entire research project and the peer review process. NR 51 TC 5 Z9 5 U1 1 U2 17 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD AUG PY 2011 VL 25 IS 8 BP 2792 EP 2803 DI 10.1096/fj.11-180729 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 800CV UT WOS:000293337800027 PM 21555356 ER PT J AU Hirsh, JM Boyle, DJ Collier, DH Oxenfeld, AJ Nash, A Quinzanos, I Caplan, L AF Hirsh, Joel M. Boyle, Dennis J. Collier, David H. Oxenfeld, Abbey J. Nash, Alyssa Quinzanos, Itziar Caplan, Liron TI Limited Health Literacy Is a Common Finding in a Public Health Hospital's Rheumatology Clinic and Is Predictive of Disease Severity SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; health literacy; patient outcome assessment ID SELF-MANAGEMENT SUPPORT; DIABETES PATIENTS; IDENTIFY PATIENTS; ARTHRITIS; ASSOCIATION; OUTCOMES; CARE; COMMUNICATION; KNOWLEDGE AB Background: Health literacy (HL) is associated with outcomes in many conditions, but little is known about its impact on arthritic diseases. Objectives: We sought to determine whether HL is related to disease activity and severity in patients with rheumatoid arthritis (RA). Methods: English-speaking adult RA patients were recruited for this cross-sectional study. Background information was ascertained by medical record review; Disease Activity Score 28 (DAS-28) scores were determined by providers; subjects completed the Multidimensional Health Assessment Questionnaire (MDHAQ), demographic questionnaires, and validated HL instruments, including the Short Test of Functional Health Literacy in Adults, Rapid Estimate of Adult Literacy in Medicine, and the single-item literacy screener. We used linear regression to assess whether HL was associated with MDHAQ and DAS-28 scores. Results: One hundred ten subjects participated in the study. Limited HL was a common finding, especially among ethnic minorities. The single-item literacy screener results were predictive of lower MDHAQ scores by univariate regression analysis. Similar trends were observed for the Short Test of Functional Health Literacy in Adults and Rapid Estimate of Adult Literacy in Medicine. The relationship between the single-item literacy screener and MDHAQ remained statistically significant in multivariate analysis that controlled for the impact of demographic features and RA disease characteristics. Health literacy scores were not associated with DAS-28 scores. Conclusions: Health literacy was independently associated with functional impairment in English-speaking RA patients at an urban safety-net clinic. This new finding suggests that RA functional status might be improved by strategies that target limited HL's causal pathways. C1 [Hirsh, Joel M.; Boyle, Dennis J.; Collier, David H.; Oxenfeld, Abbey J.; Nash, Alyssa] Denver Hlth Med Ctr, Dept Med, Div Rheumatol, Denver, CO 80204 USA. [Hirsh, Joel M.; Boyle, Dennis J.; Collier, David H.; Caplan, Liron] Univ Colorado, Sch Med, Dept Med, Div Rheumatol, Denver, CO USA. [Quinzanos, Itziar] Denver Hlth Med Ctr, Dept Gen Internal Med, Denver, CO 80204 USA. [Caplan, Liron] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. RP Hirsh, JM (reprint author), Denver Hlth Med Ctr, Dept Med, Div Rheumatol, 777 Bannock St,Mail Code 4000, Denver, CO 80204 USA. EM joel.hirshMD@dhha.org FU Denver Health Department of Medicine; VA HSRD [07-221] FX Project support provided by the Denver Health Department of Medicine. Dr. Caplan is supported by a VA HSR&D Career Development Award (07-221). NR 44 TC 18 Z9 19 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 EI 1536-7355 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD AUG PY 2011 VL 17 IS 5 BP 236 EP 241 DI 10.1097/RHU.0b013e318226a01f PG 6 WC Rheumatology SC Rheumatology GA 800PS UT WOS:000293376000003 PM 21778910 ER PT J AU Zhang, LY Schumacher, HR Su, HH Lie, D Dinnella, J Baker, JF Von Feldt, JM AF Zhang, Li Yun Schumacher, H. Ralph Su, Hou Heng Lie, Dai Dinnella, Janet Baker, Joshua F. Von Feldt, Joan M. TI Development and Evaluation of a Survey of Gout Patients Concerning Their Knowledge About Gout SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE gout; patient's knowledge; questionnaire; survey ID EVIDENCE BASED RECOMMENDATIONS; ANTIHYPERURICEMIC THERAPY; RHEUMATIC SYMPTOMS; TOPHACEOUS GOUT; TASK-FORCE; MANAGEMENT; HYPERURICEMIA; DIAGNOSIS; PREVALENCE; ARTHRITIS AB Objective: The objective of the study was to develop and test a survey of gout patients regarding their level of disease-related knowledge, to identify potential targets for patient education. Methods: A 10-item questionnaire with readability at a Flesch-Kincaid grade level of 4.6 and Flesch reading ease of 83.9% was designed to address parameters considered important for patient participation in the management of gout. The questionnaire was primarily evaluated at the Veterans Affairs (VA) Medical Center in Philadelphia, but was also secondarily performed at 2 Chinese hospitals, the Sun Yat-sen Memorial Hospital of Zhong Shan University, Guangdong Province (GZ), and the Qingdao Municipal Hospital, Qingdao City, Shandong Province (QD). Demographic and questionnaire data by institution were evaluated using descriptive statistics, and significant differences were identified by W 2 and Fisher exact tests. Patient responses were displayed by each individual question and by the distribution of total scores. Kruskal-Wallis tests of significance were used for nonparametric or skewed data. Intraclass correlations (ICCs) were performed within the VA population to determine internal consistency of the individual questions. A high score was defined as greater than 7 (the median value). Multivariate regression models using demographic and clinical characteristics attempted to identify factors associated with correct answers to each question. Results: Total correct score for individual patients varied widely at each institution with a mean (SD) and median (interquartile range [IQR]) scores in all 3 hospitals of 6.15 (2.25) and 7 (5-8), respectively. The average numbers of correct responses for each institution were 4.38 (SD, 3.04) (median, 4 [IQR, 2-7]) at GZ; 7.05 (SD, 1.37) (median, 8 [IQR, 6-8]) at QD; 6.21 (SD, 1.74) (median, 7 [IQR, 6-7]) at VA; P = 0.0010. Two questions (Q4 and Q10) were identified as difficult to understand by patients and showed poor ICC (ICC = 0.0000, P > 0.5) at the VA. Questions that were more difficult to answer were (1) Q3: What inside the joint causes attacks of gout? (GZ, 28.6%; QD, 7.7%; VA, 72.4%; P = 0.000); (2) Q8: How long should patients continue with serum uric acid-lowering drugs? (GZ, 19.1%; QD, 10.3%; VA, 82.7%; P = 0.000); (3) Q6: The ideal serum uric acid to aim at during treatment? (GZ, 42.8%; QD, 89.7%; and VA, 17.2%; P = 0.000); and (4) Q5: Which drugs can lower serum uric acid? (GZ, 61.9%; QD, 89.7%; VA, 51.7%; P = 0.002). Conclusions: This study describes an easy-to-read 10-item questionnaire that can identify important knowledge gaps in patients with gout. This can be the first step in designing educational interventions to improve patient understanding and improve clinical care. C1 [Zhang, Li Yun] Shanxi Med Univ, Hosp 2, Div Rheumatol, Taiyuan 030001, Shanxi Province, Peoples R China. [Zhang, Li Yun; Schumacher, H. Ralph; Dinnella, Janet; Baker, Joshua F.; Von Feldt, Joan M.] Univ Penn, Vet Affairs Med Ctr, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Su, Hou Heng] Qingdao Municipal Hosp, Dept Rheumatol, Qingdao, Shandong, Peoples R China. [Lie, Dai] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Rheumatol, Guangzhou 510275, Guangdong, Peoples R China. RP Zhang, LY (reprint author), Shanxi Med Univ, Hosp 2, Div Rheumatol, 382 Wuyi Rd, Taiyuan 030001, Shanxi Province, Peoples R China. EM zhangly2006@sina.com NR 32 TC 12 Z9 12 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD AUG PY 2011 VL 17 IS 5 BP 242 EP 248 DI 10.1097/RHU.0b013e318228b4e2 PG 7 WC Rheumatology SC Rheumatology GA 800PS UT WOS:000293376000004 PM 21778899 ER PT J AU Bloch, MJ Basile, JN AF Bloch, Michael J. Basile, Jan N. TI SPIRONOLACTONE IS MORE EFFECTIVE THAN EPLERENONE AT LOWERING BLOOD PRESSURE IN PATIENTS WITH PRIMARY ALDOSTERONISM SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Editorial Material C1 [Bloch, Michael J.] Univ Nevada, St Marys Reg Med Ctr, Risk Reduct Ctr, Dept Internal Med,Sch Med, Reno, NV 89503 USA. [Basile, Jan N.] Med Univ S Carolina, Seinsheimer Cardiovasc Hlth Program, Div Gen Internal Med Geriatr, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Bloch, MJ (reprint author), Univ Nevada, St Marys Reg Med Ctr, Risk Reduct Ctr, Dept Internal Med,Sch Med, 645 N Arlington St,Suite 460, Reno, NV 89503 USA. EM mbloch@aol.com NR 0 TC 0 Z9 2 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 AUG PY 2011 VL 13 IS 8 BP 629 EP 631 DI 10.1111/j.1751-7176.2011.00495.x PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 800HE UT WOS:000293349600014 PM 21806775 ER PT J AU Kofler, MJ McCart, MR Zajac, K Ruggiero, KJ Saunders, BE Kilpatrick, DG AF Kofler, Michael J. McCart, Michael R. Zajac, Kristyn Ruggiero, Kenneth J. Saunders, Benjamin E. Kilpatrick, Dean G. TI Depression and Delinquency Covariation in an Accelerated Longitudinal Sample of Adolescents SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE adolescents; depression; delinquency; acting out theory; failure theory ID CONDUCT PROBLEMS; ENVIRONMENTAL-INFLUENCES; MODELING APPROACH; MAJOR DEPRESSION; SUBSTANCE-ABUSE; CHILDHOOD; DISORDERS; SYMPTOMS; COMORBIDITY; BOYS AB Objectives: The current study tested opposing predictions stemming from the failure and acting out theories of depression-delinquency covariation. Method: Participants included a nationwide longitudinal sample of adolescents (N = 3,604) ages 12 to 17. Competing models were tested with cohort-sequential latent growth curve modeling to determine whether depressive symptoms at age 12 (baseline) predicted concurrent and age-related changes in delinquent behavior, whether the opposite pattern was apparent (delinquency predicting depression), and whether initial levels of depression predict changes in delinquency significantly better than vice versa. Results: Early depressive symptoms predicted age-related changes in delinquent behavior significantly better than early delinquency predicted changes in depressive symptoms. In addition, the impact of gender on age-related changes in delinquent symptoms was mediated by gender differences in depressive symptom changes, indicating that depressive symptoms are a particularly salient risk factor for delinquent behavior in girls. Conclusion: Early depressive symptoms represent a significant risk factor for later delinquent behavior-especially for girls-and appear to be a better predictor of later delinquency than early delinquency is of later depression. These findings provide support for the acting out theory and contradict failure theory predictions. C1 [McCart, Michael R.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Family Serv Res Ctr, Charleston, SC 29425 USA. [Kofler, Michael J.] Univ Cent Florida, Dept Psychol, Orlando, FL 32816 USA. [Ruggiero, Kenneth J.; Saunders, Benjamin E.; Kilpatrick, Dean G.] Med Univ S Carolina, Natl Crime Victims Res & Treatment Ctr, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP McCart, MR (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Family Serv Res Ctr, Charleston, SC 29425 USA. EM mccartm@musc.edu FU NICHD NIH HHS [R01 HD046830, R01HD046830] NR 46 TC 31 Z9 32 U1 3 U2 24 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 2011 VL 79 IS 4 BP 458 EP 469 DI 10.1037/a0024108 PG 12 WC Psychology, Clinical SC Psychology GA 800PZ UT WOS:000293376900005 PM 21787049 ER PT J AU Reinke, LF Slatore, CG Uman, J Udris, EM Moss, BR Engelberg, RA Au, DH AF Reinke, Lynn F. Slatore, Christopher G. Uman, Jane Udris, Edmunds M. Moss, Brianna R. Engelberg, Ruth A. Au, David H. TI Patient-Clinician Communication about End-of-Life Care Topics: Is Anyone Talking to Patients with Chronic Obstructive Pulmonary Disease? SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID ADVANCE DIRECTIVE EDUCATION; PALLIATIVE CARE; PHYSICIANS; HEALTH; CANCER; REHABILITATION; SPIRITUALITY; DISCUSSIONS; FAMILIES; OUTCOMES AB Background: Reports describe patient and health care system benefits when clinicians engage in end-of-life conversations with patients diagnosed with life-limiting illnesses, yet most clinicians focus on life-preserving treatments and avoid conversations about end-of-life care. We describe patient-clinician communication practices about end-of-life care in patients with chronic obstructive pulmonary disease (COPD) using self-report questionnaires to: (1) characterize the content of patient-clinician communication about end-of-life care from the patient perspective, including topics that were not addressed and ratings of the quality of the communication for topics discussed and (2) determine whether clinician characteristics was associated with the absence of specific communication items addressed. Methods: Cross-sectional study of outpatients (n = 376) who completed the Quality of Communication (QOC) questionnaire (outcome measure). The primary exposure was clinician training. We used logistic regression. All tests were two-tailed and p < 0.05 was considered significant. Results: Clinicians (n = 92) were staff physicians (33.7%), physician trainees (35.9%), and advanced practice nurses (30.4%). Patients were older (mean age, 69.4 years, standard deviation [SD] 10.0); white (86%) men (97%) with severe COPD (mean forced expiraory volume in 1 second [FEV(1)] percent predicted 50%, SD 20). All end-of-life topics were underaddressed. Four topics were not addressed 77%-94% of the time. None of the QOC items varied significantly by clinician type in adjusted logistic regression. Conclusions: All end-of-life communication topics were underaddressed by clinicians, regardless of training, with four topics particularly unlikely to be discussed. End-of-life topics that are important to patients should be targeted for an intervention to facilitate improvement in clinicians' communication skills and practice and may improve patient satisfaction with clinician communication. C1 [Reinke, Lynn F.; Uman, Jane; Udris, Edmunds M.; Moss, Brianna R.; Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv R&D, Seattle, WA 98101 USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland VA Med Ctr Hlth Serv Res & Dev, Portland, OR 97201 USA. [Engelberg, Ruth A.; Au, David H.] Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA USA. RP Reinke, LF (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv R&D, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM reinkl@u.washington.edu RI Oliveira, Joana\/A-8373-2012 OI Slatore, Christopher/0000-0003-0958-8122 FU Health Services Research and Development, Department of Veterans Affairs [IIR 02-292]; Department of Veterans Affairs; Veterans Health Administration; Office of Research and Development; Health Services Research and Development; VA HSRD Career Development Award; Portland VA Medical Center FX Funded by Health Services Research and Development, Department of Veterans Affairs. IIR 02-292.; This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Health Services Research and Development.; Dr. Slatore is a recipient of a VA HSRD Career Development Award and is supported by resources from the Portland VA Medical Center. NR 36 TC 23 Z9 23 U1 0 U2 15 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 AUG PY 2011 VL 14 IS 8 BP 923 EP 928 DI 10.1089/jpm.2010.0509 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 800TN UT WOS:000293390200008 PM 21631367 ER PT J AU Molis, MR Leek, MR AF Molis, Michelle R. Leek, Marjorie R. TI Vowel Identification by Listeners With Hearing Impairment in Response to Variation in Formant Frequencies SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE sensorineural hearing loss; speech perception; speech sound ID FALSE DISCOVERY RATE; SPECTRAL CONTRAST; NOTCHED-NOISE; SPEECH; DISCRIMINATION; PERCEPTION; RECOGNITION; SELECTIVITY; YOUNG; RESOLUTION AB Purpose: This study examined the influence of presentation level and mild-to-moderate hearing loss on the identification of a set of vowel tokens systematically varying in the frequency locations of their second and third formants. Method: Five listeners with normal hearing (NH listeners) and five listeners with hearing impairment (HI listeners) identified synthesized vowels that represented both highly identifiable and ambiguous examples of /I/, /U/, and /(sic)/. Results: Response patterns of NH listeners showed significant changes, with an increase in presentation level from 75 dB SPL to 95 dB SPL, including increased category overlap. HI listeners, listening only at the higher level, showed greater category overlap than normal and overall identification patterns that differed significantly from those of NH listeners. Excitation patterns based on estimates of auditory filters suggested smoothing of the internal representations, resulting in impaired formant resolution. Conclusions: Both increased presentation level for NH listeners and the presence of hearing loss produced a significant change in vowel identification for this stimulus set. Major differences were observed between NH listeners and HI listeners in vowel category overlap and in the sharpness of boundaries between vowel tokens. It is likely that these findings reflect imprecise internal spectral representations due to reduced frequency selectivity. C1 [Molis, Michelle R.; Leek, Marjorie R.] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR USA. RP Molis, MR (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR USA. EM michelle.molis@va.gov FU NIDCD NIH HHS [R01 DC000626, R01 DC000626-23, R01DC 00626] NR 43 TC 4 Z9 4 U1 0 U2 2 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD AUG 1 PY 2011 VL 54 IS 4 BP 1211 EP 1223 DI 10.1044/1092-4388(2010/09-0218) PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 800RB UT WOS:000293380900017 PM 21297168 ER PT J AU Khan, B Bauman, WA Sinha, AK Kahn, NN AF Khan, B. Bauman, W. A. Sinha, A. K. Kahn, N. N. TI Non-conventional hemostatic risk factors for coronary heart disease in individuals with spinal cord injury SO SPINAL CORD LA English DT Review DE coronary heart disease; prostacyclin; insulin; antibody; platelets ID PROSTACYCLIN RECEPTOR ANTIBODY; PLATELET-STIMULATED THROMBIN; PHYSICAL-ACTIVITY; PROSTAGLANDIN ENDOPEROXIDES; ATHEROSCLEROTIC PLAQUES; ADENYLATE-CYCLASE; GROWTH-FACTOR; NITRIC-OXIDE; INSULIN; BLOOD AB Study design: Review. Objectives: In subjects with spinal cord injury (SCI), there is strong evidence for platelet hyperactivity, which may stimulate atherosclerosis and coronary heart disease (CHD). The literature was reviewed. Background: Individuals with SCI develop premature CHD. In addition to the conventional risk factors associated with CHD, there are pathologic hematological factors involved in atherogenesis that are similar to those that have been demonstrated in individuals with diabetes, and these hematological factors might affect individuals with SCI. One such hematological factor, platelet aggregation, is essential for the development of CHD, which results from thrombus formation in the coronary vasculature. Prostacyclin (PGI(2)) is a potent inhibitor of platelet aggregation and is thought to have a beneficial role in inhibiting atherogenesis; therefore, it is possible that individuals with SCI have impaired PGI(2) receptor function. Methods: We reviewed the literature by conducting a search using PubMed (1970-2007). Results: Acute thrombosis is emerging as an important factor in the etiology of CHD and therefore could mediate the risk of CHD in persons with SCI, in addition to previously known risk factors such as hyperlipidemia, hypertension, hyperlipidemia, diabetes mellitus and hyperinsulinemia. Because PGI(2) may retard atherogenesis through its inhibitory effects on platelet function, we discuss the effects of PGI(2) on platelets in persons with SCI in this review. Conclusions Subjects with chronic SCI develop abnormal platelet function, resulting in the production of atherogenic and thrombogenic factors for the following reasons: (1) the PGI(2) and insulin receptors on their platelets are impaired; (2) thrombin generation and platelet-derived growth factor release are elevated; (3) insulin-induced nitric oxide production by platelets is markedly impaired; and (4) a circulating antibody (immunoglobulin G (IgG)) blocks the antithrombotic effect of both insulin and PGI(2) receptors. Thus, this IgG molecule is thought to be one of the pathological mediators of the increased incidence of CHD in individuals with SCI. Spinal Cord (2011) 49, 858-866; doi:10.1038/sc.2011.33; published online 24 May 2011 C1 [Bauman, W. A.; Kahn, N. N.] James J Peters Vet Affairs Med Ctr, Dept Med & Res Serv, Bronx, NY 10468 USA. [Khan, B.] Amer Univ Antigua COM, New York, NY USA. [Bauman, W. A.; Kahn, N. N.] Ctr Excellence Consequences Spinal Cord Injury, Dept Vet Affairs Rehabil Res & Dev Serv, Bronx, NY USA. [Bauman, W. A.; Sinha, A. K.; Kahn, N. N.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauman, W. A.; Kahn, N. N.] Dept Rehabil Med, New York, NY USA. RP Kahn, NN (reprint author), James J Peters Vet Affairs Med Ctr, Dept Med & Res Serv, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM nighat.kahn@med.va.gov FU Veterans Affairs Rehabilitation Research and Development Service, Center of Excellence for the Consequences of Spinal Cord Injury [B4162]; James J. Peters Veterans Affairs Medical Center FX This work was supported by the Veterans Affairs Rehabilitation Research and Development Service, Center of Excellence for the Consequences of Spinal Cord Injury (#B4162), James J. Peters Veterans Affairs Medical Center. NR 55 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 EI 1476-5624 J9 SPINAL CORD JI Spinal Cord PD AUG PY 2011 VL 49 IS 8 BP 858 EP 866 DI 10.1038/sc.2011.33 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 803HS UT WOS:000293573000002 PM 21606930 ER PT J AU Wu, Y Hou, J Collier, L Pan, J Hou, L Qin, W Bauman, WA Cardozo, CP AF Wu, Y. Hou, J. Collier, L. Pan, J. Hou, L. Qin, W. Bauman, W. A. Cardozo, C. P. TI The administration of high-dose methylprednisolone for 24 h reduced muscle size and increased atrophy-related gene expression in spinal cord-injured rats SO SPINAL CORD LA English DT Article DE spinal cord injury; methylprednisolone; muscle atrophy; muscle ubiquitin ligases; REDD1; FOXO1 ID SKELETAL-MUSCLE; PROTEIN; TESTOSTERONE; TRANSECTION; INVOLVE AB Objective: Administration after spinal cord injury (SCI) of methylprednisolone (MP) for 24-48h has been suggested to improve functional outcome. The safety of this approach has been questioned because of the known adverse effects of glucocorticoids on skeletal muscle and the immune system. The purpose of this study was to explicitly test adverse effects of regimen of MP administration on skeletal muscle. Study design: Male rats underwent spinal cord transection at T9-T10, followed by an intravenous injection of MP and subsequent infusion of MP for 24 h. Results: MP significantly reduced the weight of the triceps, soleus, plantaris and gastrocnemius muscles, with the greatest effect being a 63% decrease in triceps weight (for example, muscle above the level of lesion) at 7 days; below the level of lesion, gastrocnemius weight was reduced by 33% by SCI alone, and by 45% by SCI and MP. Centralized nuclei were found in myofibers of the gastrocnemius and triceps from the MP-SCI group, but not other groups. MP increased expression in the triceps, soleus and plantaris of FOXO1, MAFbx, MuRF1 and REDD1 at 1 day, and, in plantaris, at 7 days. Conclusions: Thus, 1 day of MP at a dose comparable to those routinely employed in clinical practice immediately after SCI resulted in marked atrophy of functionally intact muscle above the level of lesion, and worsened atrophy of paralyzed muscle below the level of lesion, associated with elevations in expression of four genes involved in pathways associated with muscle atrophy. Spinal Cord (2011) 49, 867-873; doi:10.1038/sc.2011.28; published online 29 March 2011 C1 [Wu, Y.; Hou, J.; Collier, L.; Pan, J.; Hou, L.; Qin, W.; Bauman, W. A.; Cardozo, C. P.] James J Peters VA Med Ctr, Dept Vet Affairs, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Qin, W.; Bauman, W. A.; Cardozo, C. P.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauman, W. A.; Cardozo, C. P.] Mt Sinai Sch Med, Dept Med & Rehabil Med, New York, NY USA. RP Cardozo, CP (reprint author), James J Peters VA Med Ctr, Dept Vet Affairs, Ctr Excellence Med Consequences Spinal Cord Injur, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Chris.Cardozo@mssm.edu FU Veterans Health Administration, Rehabilitation Research and Development Service [B4162C, B3347K] FX The research reported here was supported by the Veterans Health Administration, Rehabilitation Research and Development Service (B4162C and B3347K). NR 16 TC 5 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 EI 1476-5624 J9 SPINAL CORD JI Spinal Cord PD AUG PY 2011 VL 49 IS 8 BP 867 EP 873 DI 10.1038/sc.2011.28 PG 7 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 803HS UT WOS:000293573000003 PM 21445080 ER PT J AU Ross, JS Arling, G Ofner, S Roumie, CL Keyhani, S Williams, LS Ordin, DL Bravata, DM AF Ross, Joseph S. Arling, Greg Ofner, Susan Roumie, Christianne L. Keyhani, Salomeh Williams, Linda S. Ordin, Diana L. Bravata, Dawn M. TI Correlation of Inpatient and Outpatient Measures of Stroke Care Quality Within Veterans Health Administration Hospitals SO STROKE LA English DT Article DE acute stroke; healthcare; outcomes; quality of care; stroke care ID ACUTE MYOCARDIAL-INFARCTION; MORTALITY-RATES; PERFORMANCE; OUTCOMES; COMPARE AB Background and Purpose-Quality of care delivered in the inpatient and ambulatory settings may be correlated within an integrated health system such as the Veterans Health Administration. We examined the correlation between stroke care quality at hospital discharge and within 6 months postdischarge. Methods-We conducted a cross-sectional hospital-level correlation analyses of chart-abstracted data for 3467 veterans discharged alive after an acute ischemic stroke from 108 Veterans Health Administration medical centers and 2380 veterans with postdischarge follow-up within 6 months in fiscal year 2007. Four risk-standardized processes of care represented discharge care quality: prescription of antithrombotic and antilipidmic therapy, anticoagulation for atrial fibrillation, and tobacco cessation counseling along with a composite measure of defect-free care. Five risk-standardized intermediate outcomes represented postdischarge care quality: achievement of blood pressure, low-density lipoprotein, international normalized ratio, and glycosylated hemoglobin target levels, and delivery of appropriate treatment for poststroke depression along with a composite measure of achieved outcomes. Results-Median risk-standardized composite rate of defect-free care at discharge was 79%. Median risk-standardized postdischarge rates of achieving goal were 56% for blood pressure, 36% for low-density lipoprotein, 41% for international normalized ratio, 40% for glycosylated hemoglobin, and 39% for depression management and the median risk-standardized composite 6-month outcome rate was 44%. The hospital composite rate of defect-free care at discharge was correlated with meeting the low-density lipoprotein goal (r = 0.31; P = 0.007) and depression management (r = 0.27; P = 0.03) goal but was not correlated with blood pressure, international normalized ratio, glycosylated hemoglobin goals, nor with the composite measure of achieved postdischarge outcomes (probability values >0.13). Conclusions-Hospital discharge care quality was not consistently correlated with ambulatory care quality. (Stroke. 2011;42:2269-2275.) C1 [Ross, Joseph S.] Yale Univ, Sch Med, Gen Internal Med Sect, Dept Med, New Haven, CT 06520 USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Arling, Greg] Indiana Univ, Ctr Aging Res, Indianapolis, IN 46204 USA. [Arling, Greg; Williams, Linda S.; Bravata, Dawn M.] Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. [Ofner, Susan] Indiana Univ Sch Med, Dept Med, IUPUI, Div Biostat, Indianapolis, IN USA. [Roumie, Christianne L.] Vanderbilt Univ, Med Ctr, Targeted Res Enhancement Program Ctr, VHA,HSR&D,GRECC, Nashville, TN USA. Vanderbilt Univ, Med Ctr, Clin Res Training Ctr Excellence, Vet Affairs Tennessee Valley Healthcare Syst, Nashville, TN USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. [Keyhani, Salomeh] James J Peters Vet Affairs Med Ctr, VHA HSR&D Res Enhancement Award Program, Bronx, NY USA. James J Peters Vet Affairs Med Ctr, GRECC, Bronx, NY USA. Mt Sinai Sch Med, Dept Hlth Evidence & Policy, New York, NY USA. [Williams, Linda S.; Bravata, Dawn M.] Richard L Roudebush Vet Affairs Med Ctr, VHA HSR&D Stroke Qual Enhancement Res Initiat QUE, Indianapolis, IN 46202 USA. [Williams, Linda S.; Bravata, Dawn M.] Richard L Roudebush Vet Affairs Med Ctr, HSR&D Ctr Excellence Implementing Evidence Based, Indianapolis, IN 46202 USA. [Williams, Linda S.] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN USA. [Ordin, Diana L.] VHA Off Qual & Performance OQP, Washington, DC USA. [Bravata, Dawn M.] Indiana Univ Sch Med, Dept Med, Div Gen Internal Med, Indianapolis, IN USA. RP Ross, JS (reprint author), Yale Univ, Sch Med, Gen Internal Med Sect, Dept Med, POB 208093, New Haven, CT 06520 USA. EM joseph.ross@yale.edu FU VHA HSR&D Research Enhancement; Veterans Affairs (VA) Office of Quality and Performance (OQP); VA Health Services Research and Development (HSR&D) Stroke Quality Enhancement Research Initiative (QUERI) [RRP 09-184]; National Institute on Aging and by the American Federation of Aging Research [K08 AG032886] FX From the Section of General Internal Medicine (J.S.R.), Department of Medicine, Yale University School of Medicine and Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT; Indiana University Centers for Aging Research (G. A.), Indianapolis, IN; Regenstrief Institute (G. A., L. S. W., D. M. B.), Indianapolis, IN; the Division of Biostatistics (S.O.), Department of Medicine, Indiana University School of Medicine, IUPUI, Indianapolis, IN; Veterans Health Administration (VHA) Health Services Research and Development (HSR&D) Targeted Research Enhancement Program Center (C. L. R.), Geriatrics Research, Education, and Clinical Center (GRECC), and Clinical Research Training Center of Excellence, Veterans Affairs-Tennessee Valley Healthcare System and the Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; VHA HSR&D Research Enhancement Award Program and GRECC (S. K.), James J. Peters Veterans Affairs Medical Center, Bronx, NY, and the Department of Health Evidence and Policy, Mount Sinai School of Medicine, New York, NY; VHA HSR&D Stroke Quality Enhancement Research Initiative (QUERI) and the HSR&D Center of Excellence for Implementing Evidence-Based Practice (CIEBP; L. S. W., D. M. B.), Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, IN; the Department of Neurology, Indiana University School of Medicine (L. S. W.), Indianapolis, IN; the VHA Office of Quality and Performance (OQP; D.L.O.), Washington, DC; and the Division of General Internal Medicine (D. M. B.), Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.; This project was supported by the Veterans Affairs (VA) Office of Quality and Performance (OQP) and the VA Health Services Research and Development (HSR&D) Stroke Quality Enhancement Research Initiative (QUERI; RRP 09-184). J.S.R. is currently supported by the National Institute on Aging and by the American Federation of Aging Research through the Paul B. Beeson Career Development Award Program (K08 AG032886). NR 20 TC 8 Z9 8 U1 1 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 AUG PY 2011 VL 42 IS 8 BP 2269 EP 2275 DI 10.1161/STROKEAHA.110.611913 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 796UE UT WOS:000293077400036 PM 21719771 ER PT J AU Cox, M Kupersmith, J Jesse, RL Petzel, RA AF Cox, Malcolm Kupersmith, Joel Jesse, Robert L. Petzel, Robert A. TI Commentary: Building Human Capital: Discovery, Learning, and Professional Satisfaction SO ACADEMIC MEDICINE LA English DT Editorial Material ID CARE AB Physician satisfaction is an important contributor to a well-functioning health system. Mohr and Burgess report that physicians in the Veterans Health Administration (VA) who spend time in research have greater overall job satisfaction, that satisfaction tracks with aggregate facility research funding, and that satisfaction is higher among physicians working in VA facilities located on the same campus or within walking distance of an affiliated medical school. An environment conducive to research therefore not only advances science but also seems to be a key element of physician satisfaction. In addition to advancing scientific discovery and promoting greater physician satisfaction, these findings suggest that an environment of discovery and learning may yield benefits beyond specific academic endeavors and contribute more broadly to supporting health system performance. C1 [Cox, Malcolm] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Jesse, Robert L.] Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA. [Cox, Malcolm; Kupersmith, Joel; Jesse, Robert L.; Petzel, Robert A.] US Dept Vet Affairs, Washington, DC USA. RP Cox, M (reprint author), US Dept Vet Affairs 10A4D, 810 Vermont Ave NW, Washington, DC 20420 USA. EM malcolm.cox@va.gov NR 6 TC 5 Z9 5 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 AUG PY 2011 VL 86 IS 8 BP 923 EP 924 DI 10.1097/ACM.0b013e3182223b8e PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 798NK UT WOS:000293215200008 PM 21795900 ER PT J AU Choi, AI Weekley, CC Chen, SC Li, SY Tamura, MK Norris, KC Shlipak, MG AF Choi, Andy I. Weekley, Cristin C. Chen, Shu-Cheng Li, Suying Tamura, Manjula Kurella Norris, Keith C. Shlipak, Michael G. TI Association of Educational Attainment With Chronic Disease and Mortality: The Kidney Early Evaluation Program (KEEP) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Education; mortality; chronic kidney disease ID UNITED-STATES; RISK-FACTORS; LIFE EXPECTANCY; HEALTH; US; DISPARITIES; SURVIVAL; LITERACY; ADULTS; INCOME AB Background: Recent reports have suggested a close relationship between education and health, including mortality, in the United States. Study Design: Observational cohort. Setting & Participants: We studied 61,457 participants enrolled in a national health screening initiative, the National Kidney Foundation's Kidney Early Evaluation Program (KEEP). Predictor: Self-reported educational attainment. Outcomes: Chronic diseases (hypertension, diabetes, cardiovascular disease, reduced kidney function, and albuminuria) and mortality. Measurements: We evaluated cross-sectional associations between self-reported educational attainment with the chronic diseases listed using logistic regression models adjusted for demographics, access to care, behaviors, and comorbid conditions. The association of educational attainment with survival was determined using multivariable Cox proportional hazards regression. Results: Higher educational attainment was associated with a lower prevalence of each of the chronic conditions listed. In multivariable models, compared with persons not completing high school, college graduates had a lower risk of each chronic condition, ranging from 11% lower odds of decreased kidney function to 37% lower odds of cardiovascular disease. During a mean follow-up of 3.9 (median, 3.7) years, 2,384 (4%) deaths occurred. In the fully adjusted Cox model, those who had completed college had 24% lower mortality compared with participants who had completed at least some high school. Limitations: Lack of income data does not allow us to disentangle the independent effects of education from income. Conclusions: In this diverse contemporary cohort, higher educational attainment was associated independently with a lower prevalence of chronic diseases and short-term mortality in all age and race/ethnicity groups. Am J Kidney Dis. 58(2): 228-234. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Choi, Andy I.; Weekley, Cristin C.; Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Choi, Andy I.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Chen, Shu-Cheng; Li, Suying] Minneapolis Med Res Fdn Inc, Chron Dis Res Grp, Minneapolis, MN USA. [Tamura, Manjula Kurella] Stanford Univ, Sch Med, Div Nephrol, Palo Alto, CA 94304 USA. [Norris, Keith C.] Charles R Drew Univ Med & Sci, Dept Internal Med, Los Angeles, CA 90059 USA. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, Dept Med, Box 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu RI Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 FU Amgen; Abbott; Novartis; Siemens; Genentech; Genzyme; Nephroceuticals; Pfizer; Lifescan; Suplena; National Institutes of Health [MD00148, 1U54RR026138] FX KEEP is a program of the National Kidney Foundation and is supported by Amgen, Abbott, Novartis, Siemens, Genentech, Genzyme, Nephroceuticals, Pfizer, Lifescan, and Suplena. These funding sources were not involved in the design or conduct of the study. Dr Norris is supported by National Institutes of Health grants MD00148 and 1U54RR026138. NR 24 TC 16 Z9 16 U1 2 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 2011 VL 58 IS 2 BP 228 EP 234 DI 10.1053/j.ajkd.2011.02.388 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 795WU UT WOS:000293010000012 PM 21601328 ER PT J AU Gladden, JD Ahmed, MI Litovsky, SH Schiros, CG Lloyd, SG Gupta, H Denney, TS Darley-Usmar, V McGiffin, DC Dell'Italia, LJ AF Gladden, James D. Ahmed, Mustafa I. Litovsky, Silvio H. Schiros, Chun G. Lloyd, Steven G. Gupta, Himanshu Denney, Thomas S., Jr. Darley-Usmar, Victor McGiffin, David C. Dell'Italia, Louis J. TI Oxidative Stress and Myocardial Remodeling in Chronic Mitral Regurgitation SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT Conference on Southern-Society-for-Clinical-Investigation-Cardiovascular-Club Session CY FEB 18, 2011 CL New Orleans, LA SP So Soc Clin Invest Cardiovasc Club DE Oxidative stress; Xanthine oxidase; Mitral regurgitation; Left ventricular function ID XANTHINE-OXIDASE INHIBITION; INDUCED HEART-FAILURE; NITRIC-OXIDE; VOLUME-OVERLOAD; MATRIX METALLOPROTEINASES; REACTIVE OXYGEN; CARDIOMYOCYTE FUNCTION; CARDIAC-HYPERTROPHY; SIGNAL-TRANSDUCTION; EJECTION FRACTION AB Mechanisms of left ventricular (LV) dysfunction in isolated mitral regurgitation (MR) are not well understood. Vasodilator therapy in other forms of LV dysfunction reduces LV wall stress and improves LV function; however, studies in isolated MR show no beneficial effect on LV remodeling using vasodilator drugs or renin-angiotensin system blockade. Therefore, the search for new therapies that improve LV remodeling and function in isolated MR is clinically significant. Recent work in the authors' laboratory has demonstrated increased oxidants from a number of sources including the enzyme xanthine oxidase (XO) in the LV of patients with isolated MR. In addition to being a major source of reactive oxygen species, XO is linked to bioenergetic dysfunction because its substrates derive from adenosine triphosphate catabolism. Correspondingly, there was also evidence of aggregates of small mitochondria in cardiomyocytes, which is generally considered a response to bioenergetic deficit in cells. Future studies are required to determine whether XO and persistent oxidative stress are causative in maladaptive LV remodeling and offer potential therapeutic targets in ameliorating LV damage in patients with isolated MR. C1 [Gladden, James D.; Ahmed, Mustafa I.; Litovsky, Silvio H.; Lloyd, Steven G.; Gupta, Himanshu; Darley-Usmar, Victor; McGiffin, David C.; Dell'Italia, Louis J.] Univ Alabama, Dept Med, Ctr Heart Failure Res, Birmingham, AL 35294 USA. [Gladden, James D.; Ahmed, Mustafa I.; Litovsky, Silvio H.; Lloyd, Steven G.; Gupta, Himanshu; Darley-Usmar, Victor; McGiffin, David C.; Dell'Italia, Louis J.] Univ Alabama, Dept Pathol, Ctr Heart Failure Res, Birmingham, AL 35294 USA. [Gladden, James D.; Ahmed, Mustafa I.; Litovsky, Silvio H.; Lloyd, Steven G.; Gupta, Himanshu; Darley-Usmar, Victor; McGiffin, David C.; Dell'Italia, Louis J.] Univ Alabama, Dept Biostat, Ctr Heart Failure Res, Birmingham, AL 35294 USA. [Gladden, James D.; Ahmed, Mustafa I.; Litovsky, Silvio H.; Lloyd, Steven G.; Gupta, Himanshu; Darley-Usmar, Victor; McGiffin, David C.; Dell'Italia, Louis J.] Univ Alabama, Div Cardiovasc Dis, Ctr Heart Failure Res, Birmingham, AL 35294 USA. [Gladden, James D.; Ahmed, Mustafa I.; Litovsky, Silvio H.; Lloyd, Steven G.; Gupta, Himanshu; Darley-Usmar, Victor; McGiffin, David C.; Dell'Italia, Louis J.] Univ Alabama, Div Cardiovasc Surg, Ctr Heart Failure Res, Birmingham, AL USA. [Lloyd, Steven G.; Gupta, Himanshu; Dell'Italia, Louis J.] Birmingham Vet Affairs Med Ctr, Dept Med, Birmingham, AL USA. [Lloyd, Steven G.; Gupta, Himanshu; Dell'Italia, Louis J.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. [Schiros, Chun G.; Denney, Thomas S., Jr.] Auburn Univ, Samuel Ginn Coll Engn, Dept Elect & Comp Engn, Birmingham, AL USA. RP Dell'Italia, LJ (reprint author), UAB Ctr Heart Failure Res, Div Cardiol, 434 BMR2,901 19th St S, Birmingham, AL 35294 USA. EM loudell@uab.edu NR 64 TC 10 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD AUG PY 2011 VL 342 IS 2 BP 114 EP 119 DI 10.1097/MAJ.0b013e318224ab93 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 798MS UT WOS:000293212200003 PM 21795957 ER PT J AU Singal, AK Jampana, SC Anand, BS AF Singal, Ashwani K. Jampana, Sarat C. Anand, Bhupinderjit S. TI Peginterferon Alfa-2a Is Superior to Peginterferon Alfa-2b in the Treatment of Naive Patients with Hepatitis C Virus Infection: Meta-Analysis of Randomized Controlled Trials SO DIGESTIVE DISEASES AND SCIENCES LA English DT Review DE Hepatitis C virus; HCV; Pegylated interferon alfa-2a; Pegylated interferon alfa-2b; Antiviral therapy; Meta-analysis ID SUSTAINED VIROLOGICAL RESPONSE; RIBAVIRIN COMBINATION THERAPY; PEGYLATED INTERFERON ALPHA-2A; PLUS RIBAVIRIN; UNITED-STATES; MORTALITY AB Background Pegylated interferon (PEGIFN) and ribavirin combination is the standard of care for the treatment of chronic hepatitis C virus (HCV) infection. Studies comparing the efficacy and safety of PEGIFN alfa-2a and PEGIFN alfa-2b in treatment-na < ve HCV-infected patients have shown conflicting results. Aim We performed a systematic review and meta-analysis of studies comparing the efficacy and safety of PEGIFN alfa-2a and PEGIFN alfa-2b in HCV-infected patients na < ve to treatment. Methods Nine studies (five abstracts) with 3,546 patients (1,771 treated with PEGIFN alfa-2a) comparing PEGIFN alfa-2a and PEGIFN alfa-2b in treatment-na < ve HCV patients were analyzed. Efficacy outcomes were sustained virologic response (SVR) and treatment discontinuation rates due to serious adverse effects (SAE). Results Pooled data on outcomes (reported as odds ratios [ORs] with 95% confidence intervals [CIs]: [OR (95% CI)]) showed higher SVR in patients treated with PEGIFN alfa-2a as compared to treatment with PEGIFN alfa-2b [1.36 (1.07-1.73); P = 0.01]. Subgroup analysis of good quality studies on SVR in genotypes 2 and 3 also favored PEGIFN alfa-2a over PEGIFN alfa-2b (1.91 [1.09-3.37]; P = 0.02). SVR results obtained with the two types of IFN showed no impact of viral load and the presence or absence of cirrhosis. Treatment discontinuation rates due to SAE, reported in six studies (two abstracts) on 3,211 patients (1,604 treated with PEGIFN alfa-2a), were similar in the two types of PEGIFN [0.66 (0.37-1.16); P = 0.15]. Conclusions PEGIFN alfa-2a has superior efficacy with higher SVR as compared to PEGIFN alfa-2b in treatment-na < ve HCV-infected patients. The safety profile of the two types of PEGIFN was similar. C1 [Singal, Ashwani K.] Univ Texas Med Branch, Div Gastroenterol, Galveston, TX 77555 USA. [Singal, Ashwani K.; Jampana, Sarat C.] Univ Texas Med Branch, Dept Internal Med, Galveston, TX 77555 USA. [Anand, Bhupinderjit S.] Baylor Coll Med, Dept Gastroenterol & Hepatol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Singal, AK (reprint author), Univ Texas Med Branch, Div Gastroenterol, Galveston, TX 77555 USA. EM aksingal@utmb.edu NR 25 TC 18 Z9 19 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD AUG PY 2011 VL 56 IS 8 BP 2221 EP 2226 DI 10.1007/s10620-011-1765-0 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 799ON UT WOS:000293296100004 PM 21643737 ER PT J AU Janssen, DJA Curtis, JR Au, DH Spruit, MA Downey, L Schols, JMGA Wouters, EFM Engelberg, RA AF Janssen, D. J. A. Curtis, J. R. Au, D. H. Spruit, M. A. Downey, L. Schols, J. M. G. A. Wouters, E. F. M. Engelberg, R. A. TI Patient-clinician communication about end-of-life care for Dutch and US patients with COPD SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE Advance care planning; chronic obstructive pulmonary disease; communication; end-of-life care; palliative care ID OBSTRUCTIVE PULMONARY-DISEASE; CRITICALLY-ILL PATIENTS; QUALITY; HEALTH; ASSOCIATIONS; DISCUSSIONS; QUESTIONNAIRE; PERSPECTIVE; CANCER; DEATH AB Improving patient-clinician communication about end-of-life care is important in order to enhance quality of care for patients with chronic obstructive pulmonary disease (COPD). Our objective was to compare quality of patient-clinician communication about end-of-life care, and endorsement of barriers and facilitators to this communication in the Netherlands and the USA. The present study was an analysis of survey data from 122 Dutch and 391 US outpatients with COPD. We compared quality of patient-clinician communication about end-of-life care (Quality of Communication questionnaire) and barriers and facilitators to communication about end-of-life care (Barriers and Facilitators Questionnaire) between the Netherlands and the USA, controlling for patients' demographic and illness characteristics. Although Dutch patients in this study had worse lung function and disease-specific health status than US patients, Dutch patients reported lower quality of communication about end-of-life care (median score 0.0 (interquartile range 0.0-2.0) versus 1.4 (0.0-3.6); adjusted p < 0.005). Clinicians in both countries rarely discussed life-sustaining treatment preferences, prognoses, dying processes or spiritual issues. Quality of communication about end-of-life care needs to improve in the Netherlands and the USA. Future studies to improve this communication should be designed to take into account international differences and patient-specific barriers and facilitators to communication about end-of-life care. C1 [Janssen, D. J. A.; Spruit, M. A.; Wouters, E. F. M.] CIRO Ctr Expertise Chron Organ Failure, Program Dev Ctr, NL-6085 NM Horn, Netherlands. [Janssen, D. J. A.] Proteion Thuis, Horn, Netherlands. [Janssen, D. J. A.] CAPHRI, Maastricht, Netherlands. [Schols, J. M. G. A.] Maastricht Univ, Fac Hlth Med & Life Sci CAPHRI, Dept Gen Practice, Maastricht, Netherlands. [Wouters, E. F. M.] Maastricht Univ Med Ctr, Dept Resp Med, Maastricht, Netherlands. [Curtis, J. R.; Downey, L.; Engelberg, R. A.] Univ Washington, Harborview Med Ctr, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. [Au, D. H.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. RP Janssen, DJA (reprint author), CIRO Ctr Expertise Chron Organ Failure, Program Dev Ctr, Hornerheide 1, NL-6085 NM Horn, Netherlands. EM daisyjanssen@proteion.nl FU CIRO+ (Centre of Expertise for Chronic Organ Failure, Horn, the Netherlands); Proteion Thuis (Horn, the Netherlands); Netherlands Asthma Foundation (Leusden, the Netherlands) [3.4.06.082]; Stichting Wetenschapsbevordering Verpleeghuiszorg (Utrecht, The Netherlands); Health Services Research and Development, Dept of Veterans Affairs [IIR 02-292]; American Lung Association; National Heart, Lung, and Blood Institute [K24 HL068593] FX This project was part of an international research fellowship supported by CIRO+ (Centre of Expertise for Chronic Organ Failure, Horn, the Netherlands). The original Dutch study was supported by: Proteion Thuis (Horn, the Netherlands); CIRO+; grant 3.4.06.082 from the Netherlands Asthma Foundation (Leusden, the Netherlands); and Stichting Wetenschapsbevordering Verpleeghuiszorg (Utrecht, The Netherlands). The original US studies were supported by the Health Services Research and Development, Dept of Veterans Affairs (grant IIR 02-292) and the American Lung Association. J.R. Curtis was funded by a K24 Award from the National Heart, Lung, and Blood Institute (grant K24 HL068593). No funding source had any role in design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. NR 35 TC 20 Z9 20 U1 2 U2 13 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD AUG PY 2011 VL 38 IS 2 BP 268 EP 276 DI 10.1183/09031936.00157710 PG 9 WC Respiratory System SC Respiratory System GA 799IM UT WOS:000293280400009 PM 21233263 ER PT J AU Wang, YN Lee, K Ledoux, WR AF Wang, Yak-Nam Lee, Kara Ledoux, William R. TI Histomorphological Evaluation of Diabetic and Non-Diabetic Plantar Soft Tissue SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE Plantar Soft Tissue; Diabetes; Skin; Elastic Septae; Adipocyte ID STEREOLOGICAL METHODS; VERTICAL SECTIONS; SURFACE-AREA; FOOT ULCER; FAT PADS; SKIN; THICKNESS; MELLITUS; RISK; NEUROPATHY AB Background: Diabetic foot ulceration has a complex and multifactorial etiology and can involve changes in the pathophysiology of the plantar soft tissue. In the current study, histomorphological analyses of diabetic and non-diabetic plantar tissue were performed. It was hypothesized that the diabetic tissue would have thicker skin (epidermis and dermis), less interdigitation between the dermis and epidermis, thicker elastic septa and decreased adipose cell size. Materials and Methods: Two locations of the foot (the heel and the first metatarsal) were examined, both of which have been reported to be locations with a high incidence of ulceration. Stereo logical methods and quantitative morphological techniques were used to evaluate the skin thickness, interdigitation index, elastic septae thickness and adipocyte cell size. Results: The diabetic donors had a greater body mass index (BMI) than the non-diabetic donors. The diabetic tissue had significantly thicker elastic septae and dermis. However, no significant difference was observed in the interdigitation index or adipocyte size. Conclusion: These findings demonstrate that morphological changes can be evaluated histologically to give a better understanding of the pathological changes in the plantar soft tissue with diabetes. These evaluations can then be associated with biomechanical changes that occur in diabetes to provide new insight into how microstructural changes can alter macroscopic properties. Clinical Relevance: An understanding of the histomorphological changes in the soft tissue in relationship to the location on the foot could help to explain the biomechanical changes that occur in diabetes and the subsequent increase in susceptibility to breakdown. C1 [Ledoux, William R.] RR&D Ctr Excellence Limb Loss Prevent & Prosthet, VA Puget Sound, Seattle, WA 98108 USA. RP Ledoux, WR (reprint author), RR&D Ctr Excellence Limb Loss Prevent & Prosthet, VA Puget Sound, MS 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM wrledoux@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 FU NIH [IR01 DK75633-03]; Department of Veterans Affairs; RRD Service grant [A4843C]; NIDDK [P30DK017047] FX This study was supported by NIH grant IR01 DK75633-03, the Department of Veterans Affairs, RR&D Service grant A4843C, and in part by NIDDK grant P30DK017047. NR 45 TC 9 Z9 9 U1 1 U2 2 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD AUG PY 2011 VL 32 IS 8 BP 802 EP 810 DI 10.3113/FAI.2011.0802 PG 9 WC Orthopedics SC Orthopedics GA 799VM UT WOS:000293314200010 PM 22049867 ER PT J AU Thakur, PC Stuckenholz, C Rivera, MR Davison, JM Yao, JK Amsterdam, A Sadler, KC Bahary, N AF Thakur, Prakash C. Stuckenholz, Carsten Rivera, Marcus R. Davison, Jon M. Yao, Jeffrey K. Amsterdam, Adam Sadler, Kirsten C. Bahary, Nathan TI Lack of De Novo Phosphatidylinositol Synthesis Leads to Endoplasmic Reticulum Stress and Hepatic Steatosis in cdipt-Deficient Zebrafish SO HEPATOLOGY LA English DT Article ID FATTY LIVER-DISEASE; GENE-EXPRESSION; ER STRESS; CANCER; RESPONSES; LIPIDS AB Hepatic steatosis is the initial stage of nonalcoholic fatty liver disease (NAFLD) and may predispose to more severe hepatic disease, including hepatocellular carcinoma. Endoplasmic reticulum (ER) stress has been recently implicated as a novel mechanism that may lead to NAFLD, although the genetic factors invoking ER stress are largely unknown. During a screen for liver defects from a zebrafish insertional mutant library, we isolated the mutant cdipt(hi559Tg-/+) (hi559). CDIPT is known to play an indispensable role in phosphatidylinositol (PtdIns) synthesis. Here we show that cdipt is expressed in the developing liver, and its disruption in hi559 mutants abrogates de novo PtdIns synthesis, resulting in hepatomegaly at 5 days postfertilization. The hi559 hepatocytes display features of NAFLD, including macrovesicular steatosis, ballooning, and necroapoptosis. Gene set enrichment of microarray profiling revealed significant enrichment of endoplasmic reticulum stress response (ERSR) genes in hi559 mutants. ER stress markers, including atf6, hspa5, calr, and xbp1, are selectively up-regulated in the mutant liver. The hi559 expression profile showed significant overlap with that of mammalian hepatic ER stress and NAFLD. Ultrastructurally, the hi559 hepatocytes display marked disruption of ER architecture with hallmarks of chronic unresolved ER stress. Induction of ER stress by tunicamycin in wild-type larvae results in a fatty liver similar to hi559, suggesting that ER stress could be a fundamental mechanism contributing to hepatic steatosis. Conclusion: cdipt-deficient zebrafish exhibit hepatic ER stress and NAFLD pathologies, implicating a novel link between PtdIns, ER stress, and steatosis. The tractability of hi559 mutant provides a valuable tool to dissect ERSR components, their contribution to molecular pathogenesis, and evaluation of novel therapeutics of NAFLD. (HEPATOLOGY 2011; 54:452-462) C1 [Thakur, Prakash C.; Stuckenholz, Carsten; Bahary, Nathan] Univ Pittsburgh, Div Hematol Oncol, Dept Med, Pittsburgh, PA 15260 USA. [Rivera, Marcus R.] Univ Pittsburgh, Childrens Hosp, Div Pediat Gastroenterol, Pittsburgh, PA 15260 USA. [Davison, Jon M.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15260 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Med, Med Res Serv, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Med, Dept Pharmaceut Sci, Pittsburgh, PA 15260 USA. [Bahary, Nathan] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15260 USA. [Amsterdam, Adam] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Sadler, Kirsten C.] Mt Sinai Sch Med, Dept Med Liver Dis, New York, NY USA. RP Bahary, N (reprint author), Univ Pittsburgh, Div Hematol Oncol, Dept Med, Biomed Sci Tower 3,Room 5058,3501 5th Ave, Pittsburgh, PA 15260 USA. EM bahary@pitt.edu RI Thakur, Prakash/H-7398-2012 FU Department of Veterans Affairs Senior Research; Cancer Center Support [P30CA047904]; National Institutes of Health [R21DK073177] FX Supported by a Department of Veterans Affairs Senior Research Career Scientist Award (to J. K. Y.), Cancer Center Support Grant P30CA047904, and National Institutes of Health Grant R21DK073177 (to N.B.). NR 38 TC 31 Z9 34 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 2011 VL 54 IS 2 BP 452 EP 462 DI 10.1002/hep.24349 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 800BT UT WOS:000293333300010 PM 21488074 ER PT J AU Schutzer, WE Beard, DR Reed, JF Mader, SL AF Schutzer, William E. Beard, Douglas R. Reed, John F. Mader, Scott L. TI Characterization of Clonal Vascular Smooth Muscle Cell Lines Derived from Young and Old Fischer 344 Rats SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE Aging; Adrenergic, beta; Fischer 344; Clonal Selection; cAMP; Cell culture; Isoproterenol; Vascular; G protein-coupled receptor kinase ID BETA-ADRENERGIC RESPONSIVENESS; AGE-RELATED-CHANGES; RECEPTOR KINASES; GENE-EXPRESSION; AORTA AB A significant finding with aging humans (and aging animal models) is that blood vessels lose their ability to respond to beta-adrenergic receptor stimuli. Therefore, they produce less cyclic adenosine monophosphate (cAMP) and have decreased vasorelaxation with advancing age. This change likely contributes to hypertension, insufficient blood flow, and atherosclerosis. Our goal was to develop a vascular smooth muscle cell culture model that replicates the molecular and biochemical changes observed in blood vessels with advancing age. A clonal selection strategy was used to produce cell lines from 2-, 6-, 12-, and 24-month-old male Fischer 344 rat aortae. Cultures were validated as smooth muscle cells with immunocytochemistry positive for alpha-actin and negative for von Willebrand factor VIII. Positive staining for G protein-coupled receptor kinase 2 indicated presence of this adrenergic receptor regulator. A total of n = 5 clones from n = 7 animals for each age group were initially analyzed for cAMP accumulation under three conditions: basal, isoproterenol stimulated, and forskolin stimulated. Results found that at passage 3, there was a significant reduction in cAMP accumulation to isoproterenol. However, this reduction disappeared by passage 6. Secondary analysis segregated clones into phenotypic age groups independent of donor animal age. Segregation identified n = 3 clones per group. At passage 3, the age-related change in the beta-adrenergic change was magnified. However, even with segregation, the adrenergic response was lost by passage 6. Our results show that early passaged clonal vascular smooth muscle cell cultures maintain their aging, adrenergic phenotype. Two separate strategies to identify age-representative phenotypes into later passage were unsuccessful. C1 [Schutzer, William E.; Beard, Douglas R.; Reed, John F.; Mader, Scott L.] Portland VA Med Ctr, Res Serv, Portland, OR 97201 USA. [Schutzer, William E.; Mader, Scott L.] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97239 USA. RP Mader, SL (reprint author), Portland VA Med Ctr, Res Serv, R&D 26,3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM scott.mader@va.gov FU Research Service, Department of Veterans Affairs; Northwest Health Foundation FX This work was supported by the Research Service, Department of Veterans Affairs, and the Northwest Health Foundation. NR 22 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD AUG PY 2011 VL 47 IS 7 BP 445 EP 450 DI 10.1007/s11626-011-9430-7 PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 797OI UT WOS:000293136800005 ER PT J AU Budde, LE Guthrie, KA Till, BG Press, OW Chauncey, TR Pagel, JM Petersdorf, SH Bensinger, WI Holmberg, LA Shustov, AR Green, DJ Maloney, DG Gopal, AK AF Budde, Lihua E. Guthrie, Katherine A. Till, Brian G. Press, Oliver W. Chauncey, Thomas R. Pagel, John M. Petersdorf, Steven H. Bensinger, William I. Holmberg, Leona A. Shustov, Andrei R. Green, Damian J. Maloney, David G. Gopal, Ajay K. TI Mantle Cell Lymphoma International Prognostic Index but Not Pretransplantation Induction Regimen Predicts Survival for Patients With Mantle-Cell Lymphoma Receiving High-Dose Therapy and Autologous Stem-Cell Transplantation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROGRESSION-FREE SURVIVAL; 1ST REMISSION; HYPER-CVAD; IMMUNOCHEMOTHERAPY; RITUXIMAB; RESCUE; TRIAL; MIPI; MCL AB Purpose High-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) are frequently used in an attempt to improve outcome in patients with mantle-cell lymphoma (MCL); however, the importance of intensive induction regimens before transplantation is unknown. Patients and Methods To address this question, we evaluated baseline characteristics, time to treatment, induction regimen, disease status at the time of transplantation, and MIPI score at diagnosis and their associations with survival in 118 consecutive patients with MCL who received HDT and ASCT at our centers. Results The MIPI was independently associated with survival after transplantation in all 118 patients (hazard ratio [HR], 3.5; P < .001) and in the 85 patients who underwent ASCT as initial consolidation (HR, 7.2; P < .001). Overall survival rates were 93%, 60%, and 32% at 2.5 years from ASCT for all patients with low-, intermediate-, and high-risk MIPI, respectively. Low-risk MIPI scores were more common in the intensive induction group than the standard induction group in all patients (64% v 46%, respectively; P = .03) and in the initial consolidation group (66% v 45%, respectively; P = .03). After adjustment for the MIPI, an intensive induction regimen was not associated with improved survival after transplantation in all patients (HR, 0.5; P = .10), the initial consolidation group (HR, 1.1; P = .86), or patients <= 60 years old (HR, 0.6; P = .50). Observation of more than 3 months before initiating therapy did not yield inferior survival (HR, 2.1; P = .12) after adjustment for the MIPI in patients receiving ASCT. Conclusion An intensive induction regimen before HDT and ASCT was not associated with improved survival after adjusting for differences in MIPI scores at diagnosis. C1 [Budde, Lihua E.; Guthrie, Katherine A.; Till, Brian G.; Press, Oliver W.; Chauncey, Thomas R.; Pagel, John M.; Petersdorf, Steven H.; Bensinger, William I.; Holmberg, Leona A.; Shustov, Andrei R.; Green, Damian J.; Maloney, David G.; Gopal, Ajay K.] Univ Washington, Seattle, WA 98195 USA. [Budde, Lihua E.; Guthrie, Katherine A.; Till, Brian G.; Press, Oliver W.; Chauncey, Thomas R.; Pagel, John M.; Petersdorf, Steven H.; Bensinger, William I.; Holmberg, Leona A.; Shustov, Andrei R.; Green, Damian J.; Maloney, David G.; Gopal, Ajay K.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Chauncey, Thomas R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Gopal, AK (reprint author), 825 Eastlake Ave E,G3-200, Seattle, WA 98109 USA. EM agopal@u.washington.edu FU National Institutes of Health [PO1CA44991]; Lymphoma Research Foundation Mantle Cell Lymphoma Initiative; Leukemia and Lymphoma Society; Mary A. Wright Memorial Research Fund FX Supported by National Institutes of Health Grant No. PO1CA44991, the Lymphoma Research Foundation Mantle Cell Lymphoma Initiative, Specialized Center of Research Grant No. 7040 from the Leukemia and Lymphoma Society, the Mary A. Wright Memorial Research Fund, and a donation from Frank and Betty Vandermeer. L.E.B. is a Special Fellow in Clinical Research of the Leukemia and Lymphoma Society. A.K.G. is a Scholar in Clinical Research of the Leukemia and Lymphoma Society. NR 19 TC 41 Z9 44 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 AUG 1 PY 2011 VL 29 IS 22 BP 3023 EP 3029 DI 10.1200/JCO.2010.33.7055 PG 7 WC Oncology SC Oncology GA 798PG UT WOS:000293222200021 PM 21730271 ER PT J AU Tomatis, C Taramona, C Rizo-Patron, E Hernandez, F Rodriguez, P Piscoya, A Gonzales, E Gotuzzo, E Heudebert, G Centor, RM Estrada, CA AF Tomatis, Cristina Taramona, Claudia Rizo-Patron, Emiliana Hernandez, Fiorela Rodriguez, Patricia Piscoya, Alejandro Gonzales, Elsa Gotuzzo, Eduardo Heudebert, Gustavo Centor, Robert M. Estrada, Carlos A. TI Evidence-based medicine training in a resource-poor country, the importance of leveraging personal and institutional relationships SO JOURNAL OF EVALUATION IN CLINICAL PRACTICE LA English DT Article DE developing countries; education; evidence-based medicine; evidence-based practice; international cooperation ID PUBLIC-HEALTH; CLINICAL-PRACTICE; DEVELOPING-WORLD; SELF-ASSESSMENT; CAPACITY; PRACTITIONERS; KNOWLEDGE; ATTITUDES; SETTINGS; PROGRAMS AB Rationale, aims and objectives Efforts to implement evidence-based medicine (EBM) training in developing countries are limited. We describe the results of an international effort to improve research capacity in a developing country; we conducted a course aimed at improving basic EBM attitudes and identified challenges. Method Between 2005 and 2009, we conducted an annual 3-day course in Peru consisting of interactive lectures and case-based workshops. We assessed self-reported competence and importance in EBM using a Likert scale (1 = low, 5 = high). Results Totally 220 clinicians participated. For phase I (2005-2007), self-reported EBM competence increased from a median of 2 to 3 (P < 0.001) and the perceived importance of EBM did not change (median = 5). For phase II (2008-2009), before the course, 8-72% graded their competence very low (score of 1-2). After the course, 67-92% of subjects graded their increase in knowledge very high (score of 4-5). The challenges included limited availability of studies relevant to the local reality written in Spanish, participants' limited time and lack of long-term follow-up on practice change. Informal discussion and written evaluation from participants were universally in agreement that more training in EBM is needed. Conclusions In an EBM course in a resource-poor country, the baseline self-reported competence and experience on EBM were low, and the course had measurable improvements of self-reported competence, perceived utility and readiness to incorporate EBM into their practices. Similar to developed countries, translational research and building the research capacity in developing countries is critical for translating best available evidence into practice. C1 [Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, REAP Ctr Surg Med Acute Care Res & Transit, Deep S Ctr Effectiveness, Vet Affairs Natl Qual Scholars Program, Birmingham, AL 35294 USA. [Tomatis, Cristina; Taramona, Claudia; Rizo-Patron, Emiliana; Hernandez, Fiorela; Rodriguez, Patricia] Univ Peruana Cayetano Heredia, Lima, Peru. [Piscoya, Alejandro] Hosp Nacl Cayetano Heredia, Lima, Peru. [Gonzales, Elsa; Gotuzzo, Eduardo] Alexander von Humboldt Univ Peruana Cayetano Here, Inst Med Trop, Lima, Peru. [Heudebert, Gustavo] Univ Alabama, Internal Med Residency Program, Birmingham, AL USA. [Heudebert, Gustavo] Univ Alabama, Fac Dev, Birmingham, AL USA. [Heudebert, Gustavo; Centor, Robert M.; Estrada, Carlos A.] Univ Alabama, Div Gen Internal Med, Birmingham, AL USA. RP Estrada, CA (reprint author), Birmingham Vet Affairs Med Ctr, REAP Ctr Surg Med Acute Care Res & Transit, Deep S Ctr Effectiveness, Vet Affairs Natl Qual Scholars Program, Birmingham, AL 35294 USA. EM cestrada@uab.edu OI Piscoya, Alejandro/0000-0002-4420-2419 FU Peru ICOHRTA Network for AIDS/TB Research Training; Fogarty International Center [1U2RTW007368-01A1] FX We thank Dr Pedro Legua for providing logistical support and funding from Peru ICOHRTA Network for AIDS/TB Research Training. Grant 1U2RTW007368-01A1 - Fogarty International Center to Dr Gotuzzo. NR 54 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1356-1294 J9 J EVAL CLIN PRACT JI J. Eval. Clin. Pract. PD AUG PY 2011 VL 17 IS 4 BP 644 EP 650 DI 10.1111/j.1365-2753.2011.01635.x PG 7 WC Health Care Sciences & Services; Medical Informatics; Medicine, General & Internal SC Health Care Sciences & Services; Medical Informatics; General & Internal Medicine GA 798SO UT WOS:000293232400017 PM 21276140 ER PT J AU Kasinath, BS Feliers, D AF Kasinath, Balakuntalam S. Feliers, Denis TI The complex world of kidney microRNAs SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID GROWTH-FACTOR-BETA; DIABETIC-NEPHROPATHY; TRANSLATION; EXPRESSION AB MicroRNAs are short noncoding RNAs that usually reduce translation of messenger RNAs. Changes in microRNA-192 (miR-192) are reported in states of renal fibrosis. New evidence supports a role for miR-192 and its target miR-200b/c in transforming growth factor-beta 1 regulation of its own expression and that of collagens in mesangial cells, with a possible role in diabetic nephropathy. As there is controversy on the role of these microRNAs in diabetic nephropathy, more work is needed. Kidney International (2011) 80, 334-337. doi:10.1038/ki.2011.165 C1 [Kasinath, Balakuntalam S.; Feliers, Denis] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Kasinath, BS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, S Texas Vet Hlth Care Syst, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Kasinath@uthscsa.edu FU NIA NIH HHS [RC2 AG036613]; NIDDK NIH HHS [DK077295, R01 DK077295] NR 11 TC 16 Z9 17 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD AUG PY 2011 VL 80 IS 4 BP 334 EP 337 DI 10.1038/ki.2011.165 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 799DX UT WOS:000293264900004 PM 21799505 ER PT J AU Wang, SY Kamat, A Pergola, P Swamy, A Tio, F Cusi, K AF Wang, Shaoyun Kamat, Amrita Pergola, Pablo Swamy, Anita Tio, Fermin Cusi, Kenneth TI Metabolic factors in the development of hepatic steatosis and altered mitochondrial gene expression in vivo SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID FATTY LIVER-DISEASE; INTRAHEPATIC TRIGLYCERIDE CONTENT; TISSUE INSULIN-RESISTANCE; PLACEBO-CONTROLLED TRIAL; NONALCOHOLIC STEATOHEPATITIS; ADIPOSE-TISSUE; COACTIVATOR PGC-1; PPAR-ALPHA; ADIPONECTIN RECEPTORS; DIABETES-MELLITUS AB The objective of the study was to understand the role in vivo of elevated plasma free fatty acids (FFA), insulin, and glucose levels in the development of steatosis and altered mitochondrial gene/protein expression. We studied 4 groups of Sprague-Dawley rats: (1) high-fat diet (HFD), (2) high-dose streptozotocin-induced diabetes (T1DM), (3) low-dose streptozotocin-induced diabetic rats on an HFD (T2DM), and (4) controls. Liver histology and expression of genes/proteins related to mitochondrial fatty acid oxidation and biogenesis were analyzed. Despite an attempt to compensate by increasing expression of genes of fatty acid oxidation (carnitine palmitoyl transferase-l/medium chain acyl-CoA dehydrogenase), the HFD and diabetic groups developed marked steatosis and suffered a significant reduction in mitochondrial biogenesis gene expression (nuclear respiratory factor 11 transcriptional factor A, mitochondrial). In T2DM rats, the combination of high glucose and FFA unexpectedly did not lead to greater fat accumulation than HFD alone. Greater steatosis in HFD vs T2DM (P < .001) correlated with impairment in the gene expression of PPAR-alpha (ie, fatty acid oxidation) and PGCl alpha, a major coactivator for mitochondrial biogenesis. Steatosis was not severe in insulin-deficient T1DM rats despite very elevated FFA and glucose levels. Increased carnitine palmitoyl transferase-1/medium chain acyl-CoA dehydrogenase/PPAR-alpha gene expression suggested inadequate adaptation to high FFA in both T1DW/T2DM rats. Hyperinsulinemia combined with elevated FFA is the key metabolic factor driving hepatic lipogenesis in vivo (HFD rats). Mitochondrial biogenesis (nuclear respiratory factor 1; transcriptional factor A, mitochondrial) is highly susceptible to FFA-induced steatosis. In contrast, hyperglycemia does not have an additive effect (T2DM) and leads to only a modest degree of steatosis in the absence of hyperinsulinemia, even when FFA are extremely elevated as in T1DM rats. (C) 2011 Elsevier Inc. All rights reserved. C1 [Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, Dept Med, Audie L Murphy Vet Adm Med Ctr, San Antonio, TX 78229 USA. RP Cusi, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, Dept Med, Audie L Murphy Vet Adm Med Ctr, San Antonio, TX 78229 USA. EM cusi@uthscsa.edu FU Burroughs Wellcome Fund; American Diabetes Association; Veterans Affairs Medical Research Fund; American Heart Association; South Central Affiliate; National Center for Research Resources [UL 1RR025767] FX We would like to thank Sergio Garcia for his assistance with the animal work. The project described was supported by the Burroughs Wellcome Fund, the American Diabetes Association, and the Veterans Affairs Medical Research Fund (Kenneth Cusi); by a Grant in Aid Award from the American Heart Association, South Central Affiliate (Pablo Pergola, MD, and Amrita Kamat, PhD); and by Award Number UL 1RR025767 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources of the National Institutes of Health. NR 62 TC 29 Z9 29 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD AUG PY 2011 VL 60 IS 8 BP 1090 EP 1099 DI 10.1016/j.metabol.2010.12.001 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 799AW UT WOS:000293256900006 PM 21310443 ER PT J AU Gold, MC Lewinsohn, DM AF Gold, Marielle C. Lewinsohn, David M. TI Mucosal associated invariant T cells and the immune response to infection SO MICROBES AND INFECTION LA English DT Review DE Mucosal associated invariant T (MAIT) cells; iNKT cells; MR1; MHC-I; Mucosal immunity; Mycobacterium tuberculosis ID MR1 ANTIGEN PRESENTATION; MAIT CELLS; CRYSTAL-STRUCTURE; ALPHA-CHAIN; GENES; TCR; RECOGNITION; EXPRESSION; MOLECULES; SYMBIOSIS AB Mucosal associated invariant T cells are unique T cells localized at high frequencies at the portals of entry for many pathogens. Mucosal associated invariant T cells display a variety of characteristics that suggest their function is to act as effectors in the initial control of microbial infection at mucosal sites. Published by Elsevier Masson SAS on behalf of Institut Pasteur. C1 [Gold, Marielle C.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Gold, Marielle C.; Lewinsohn, David M.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Gold, MC (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,Mail Code VA R&D 11, Portland, OR 97239 USA. EM goldm@ohsu.edu RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494; Gold, Marielle/0000-0003-2505-3291 FU NIAID NIH HHS [R01 AI078965, U01 AI095776, R01 AI078965-01A2] NR 42 TC 10 Z9 10 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD AUG PY 2011 VL 13 IS 8-9 BP 742 EP 748 DI 10.1016/j.micinf.2011.03.007 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 797IS UT WOS:000293118300003 PM 21458588 ER PT J AU Bartzokis, G AF Bartzokis, George TI Alzheimer's disease as homeostatic responses to age-related myelin breakdown SO NEUROBIOLOGY OF AGING LA English DT Review DE Aging; Oligodendrocyte; Peroxisome; BACE; Neuregulin; Apolipoprotein; Prevention; Ubiquitin; alpha-Synuclein; TDP-43; FTLD ID AMYLOID PRECURSOR PROTEIN; GROWTH-FACTOR-I; CENTRAL-NERVOUS-SYSTEM; AMYOTROPHIC-LATERAL-SCLEROSIS; FAST AXONAL-TRANSPORT; FRONTOTEMPORAL LOBAR DEGENERATION; 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE; ETHANOLAMINE PLASMALOGEN DEFICIENCY; MYELOGENETIC CORTICAL LOCALIZATION; POLYUNSATURATED FATTY-ACIDS AB The amyloid hypothesis (AH) of Alzheimer's disease (AD) posits that the fundamental cause of AD is the accumulation of the peptide amyloid beta(A beta) in the brain. This hypothesis has been supported by observations that genetic defects in amyloid precursor protein (APP) and presenilin increase A beta production and cause familial AD (FAD). The AH is widely accepted but does not account for important phenomena including recent failures of clinical trials to impact dementia in humans even after successfully reducing A beta deposits. Herein, the AH is viewed from the broader overarching perspective of the myelin model of the human brain that focuses on functioning brain circuits and encompasses white matter and myelin in addition to neurons and synapses. The model proposes that the recently evolved and extensive myelination of the human brain underlies both our unique abilities and susceptibility to highly prevalent age-related neuropsychiatric disorders such as late onset AD (LOAD). It regards oligodendrocytes and the myelin they produce as being both critical for circuit function and uniquely vulnerable to damage. This perspective reframes key observations such as axonal transport disruptions, formation of axonal swellings/sphenoids and neuritic plaques, and proteinaceous deposits such as A beta and tau as by-products of homeostatic myelin repair processes. It delineates empirically testable mechanisms of action for genes underlying FAD and LOAD and provides" upstream" treatment targets. Such interventions could potentially treat multiple degenerative brain disorders by mitigating the effects of aging and associated changes in iron, cholesterol, and free radicals on oligodendrocytes and their myelin. (C) 2009 Elsevier Inc. All rights reserved. C1 [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Lab Neuroimaging, Dept Neurol,Div Brain Mapping, Los Angeles, CA 90095 USA. [Bartzokis, George] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. RP Bartzokis, G (reprint author), 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 FU NIH [MH066029, AG027342]; RCS Alzheimer's Foundation; Department of Veterans Affairs Research and Psychiatry Services FX Part of this work was supported by NIH grants (MH066029 and AG027342); the RCS Alzheimer's Foundation; and the Department of Veterans Affairs Research and Psychiatry Services. NR 437 TC 148 Z9 152 U1 5 U2 48 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD AUG PY 2011 VL 32 IS 8 BP 1341 EP 1371 DI 10.1016/j.neurobiolaging.2009.08.007 PG 31 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 796CT UT WOS:000293028500001 PM 19775776 ER PT J AU Renker, M Nance, JW Schoepf, UJ O'Brien, TX Zwerner, PL Meyer, M Kerl, JM Bauer, RW Fink, C Vogl, TJ Henzler, T AF Renker, Matthias Nance, John W., Jr. Schoepf, U. Joseph O'Brien, Terrence X. Zwerner, Peter L. Meyer, Mathias Kerl, J. Matthias Bauer, Ralf W. Fink, Christian Vogl, Thomas J. Henzler, Thomas TI Evaluation of Heavily Calcified Vessels with Coronary CT Angiography: Comparison of Iterative and Filtered Back Projection Image Reconstruction SO RADIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; DUAL-SOURCE CT; HEART-RATE-VARIABILITY; EX-VIVO MODEL; DIAGNOSTIC-ACCURACY; ARTERY-DISEASE; QUALITY; METAANALYSIS; PERFORMANCE; MORTALITY AB Purpose: To prospectively compare traditional filtered back projection (FBP) and iterative image reconstruction for the evaluation of heavily calcified arteries with coronary computed tomography (CT) angiography. Materials and Methods: The study had institutional review board approval and was HIPAA compliant. Written informed consent was obtained from all patients. Fifty-five consecutive patients (35 men, 20 women; mean age, 58 years +/- 12 [standard deviation]) with Agatston scores of at least 400 underwent coronary CT angiography and cardiac catheterization. Image data were reconstructed with both FBP and iterative reconstruction techniques with corresponding cardiac algorithms. Image noise and subjective image quality were compared. To objectively assess the effect of FBP and iterative reconstruction on blooming artifacts, volumes of circumscribed calcifications were measured with dedicated volume analysis software. FBP and iterative reconstruction series were independently evaluated for coronary artery stenosis greater than 50%, and their diagnostic accuracy was compared, with cardiac catheterization as the reference standard. Statistical analyses included paired t tests, Kruskal-Wallis analysis of variance, and a modified McNemar test. Results: Image noise measured significantly lower (P = .011-.035) with iterative reconstruction instead of FBP. Image quality was rated significantly higher (P = .031 and .042) with iterative reconstruction series than with FBP. Calcification volumes measured significantly lower (P = .019 and .026) with iterative reconstruction (44.3 mm(3) +/- 64.7 and 46.2 mm(3) +/- 68.8) than with FBP (54.5 mm(3) +/- 69.5 and 56.3 mm(3) +/- 72.5). Iterative reconstruction significantly improved some measures of per-segment diagnostic accuracy of coronary CT angiography for the detection of significant stenosis compared with FBP (accuracy: 95.9% vs 91.8%, P = .0001; specificity: 95.8% vs 91.2%, P = .0001; positive predictive value: 76.9% vs 61.1%, P = .0001). Conclusion: Iterative reconstruction reduces image noise and blooming artifacts from calcifications, leading to improved diagnostic accuracy of coronary CT angiography in patients with heavily calcified coronary arteries. (C) RSNA, 2011 C1 [Renker, Matthias; Nance, John W., Jr.; Schoepf, U. Joseph; O'Brien, Terrence X.; Zwerner, Peter L.; Meyer, Mathias; Kerl, J. Matthias; Bauer, Ralf W.; Fink, Christian; Henzler, Thomas] Med Univ S Carolina, Heart & Vasc Ctr, Charleston, SC 29425 USA. [Renker, Matthias; Kerl, J. Matthias; Bauer, Ralf W.; Vogl, Thomas J.] Goethe Univ Frankfurt, Dept Radiol, Frankfurt, Germany. [O'Brien, Terrence X.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Meyer, Mathias; Fink, Christian; Henzler, Thomas] Univ Heidelberg, Inst Clin Radiol & Nucl Med, Univ Med Ctr Mannheim, D-6800 Mannheim, Germany. RP Schoepf, UJ (reprint author), Med Univ S Carolina, Heart & Vasc Ctr, Ashley River Tower,25 Courtenay Dr, Charleston, SC 29425 USA. EM schoepf@musc.edu RI Meyer, Mathias/G-6791-2015 FU Department of Veterans Affairs FX From the Heart and Vascular Center, Medical University of South Carolina, Ashley River Tower, 25 Courtenay Dr, Charleston, SC 29425-2260 (M. R., J.W.N., U.J.S., T.X.O., P.L.Z., M. M., J.M.K., R. W. B., C. F., T. H.); Department of Radiology, Johann Wolfgang Goethe University, Frankfurt, Germany (M. R., J.M.K., R. W. B., T.J.V.); Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (T.X.O.); and Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany (M. M., C. F., T. H.). Received December 30, 2010; revision requested February 28, 2011; revision received March 18; accepted April 2; final version accepted April 20. Supported in part by the Research and Development Program of the Department of Veterans Affairs. Address correspondence to U.J.S. (e-mail: schoepf@musc.edu). NR 38 TC 91 Z9 98 U1 0 U2 8 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2011 VL 260 IS 2 BP 390 EP 399 DI 10.1148/radiol.11103574 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 795TU UT WOS:000292999600009 PM 21693660 ER PT J AU Cavusoglu, E Marmur, JD Hojjati, MR Chopra, V Butala, M Subnani, R Huda, MS Yanamadala, S Ruwende, C Eng, C Pinsky, DJ AF Cavusoglu, Erdal Marmur, Jonathan D. Hojjati, Mohammad R. Chopra, Vineet Butala, Mitul Subnani, Rakesh Huda, Mohammad S. Yanamadala, Sunitha Ruwende, Cyril Eng, Calvin Pinsky, David J. TI Plasma Interleukin-10 Levels and Adverse Outcomes in Acute Coronary Syndrome SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Acute coronary syndrome; Biomarker; Inflammation; Interleukin-10; Prognosis ID ANTIINFLAMMATORY CYTOKINE INTERLEUKIN-10; C-REACTIVE PROTEIN; MYOCARDIAL-INFARCTION; INDEPENDENT PREDICTOR; CARDIAC MORTALITY; ADIPONECTIN; DISEASE AB PURPOSE OR BACKGROUND: Interleukin (IL)-10 is an immunoregulatory cytokine that is produced by a variety of cell types, such as macrophages and activated monocytes. IL-10 possesses numerous anti-inflammatory, anti-thrombotic and anti-atherosclerotic properties. Furthermore, patients with acute coronary syndrome have been demonstrated to have reduced levels of IL-10 compared to their stable counterparts. For these reasons, it has been proposed that IL-10 plays a protective role in both atherogenesis and plaque vulnerability. However, 2 short-term studies on the prognostic utility of IL-10 in patients with acute coronary syndrome have provided conflicting results, with one study showing that reduced levels of IL-10 were predictors of adverse outcomes and another showing that elevated levels predicted poor outcomes. The objective of the present study was to investigate the long-term prognostic significance of baseline IL-10 levels in patients with acute coronary syndrome. METHODS: Baseline plasma IL-10 levels were measured in 193 well-characterized male patients with acute coronary syndrome who were referred for coronary angiography and followed prospectively for 5 years for the development of major adverse cardiovascular events. RESULTS: After controlling for a variety of baseline variables (including established biomarkers such as high-sensitivity C-reactive protein and N-terminal-pro-B-type natriuretic peptide), plasma IL-10 levels (whether analyzed as a continuous variable or as a categorical variable using receiver operating characteristic-derived cut point) were a strong and independent predictor of the composite outcome of death or non-fatal myocardial infarction when using a Cox proportional hazards model. CONCLUSIONS: These data demonstrate that, despite biologic plausibility for IL-10 as being a cardioprotective cytokine, elevated baseline plasma levels of IL-10 are a strong and independent predictor of long-term adverse cardiovascular outcomes in patients with acute coronary syndrome. Published by Elsevier Inc. The American Journal of Medicine (2011) 124, 724-730 C1 [Cavusoglu, Erdal; Marmur, Jonathan D.; Hojjati, Mohammad R.; Butala, Mitul; Subnani, Rakesh; Huda, Mohammad S.] Suny Downstate Med Ctr, Div Cardiol, Dept Med, Brooklyn, NY 11203 USA. [Cavusoglu, Erdal; Chopra, Vineet; Eng, Calvin] Bronx Vet Affairs Med Ctr, Dept Med, Div Cardiol, Bronx, NY USA. [Yanamadala, Sunitha; Ruwende, Cyril; Pinsky, David J.] Univ Michigan, Dept Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. RP Cavusoglu, E (reprint author), Suny Downstate Med Ctr, Div Cardiol, Dept Med, 450 Clarkson Ave,Box 1257, Brooklyn, NY 11203 USA. EM ECavusoglu@aol.com NR 18 TC 30 Z9 33 U1 0 U2 2 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 AUG PY 2011 VL 124 IS 8 BP 724 EP 730 DI 10.1016/j.amjmed.2011.02.040 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 795WV UT WOS:000293010100024 PM 21787901 ER PT J AU Brondolo, E Hausmann, LRM Jhalani, J Pencille, M Atencio-Bacayon, J Kumar, A Kwok, J Ullah, J Roth, A Chen, D Crupi, R Schwartz, J AF Brondolo, Elizabeth Hausmann, Leslie R. M. Jhalani, Juhee Pencille, Melissa Atencio-Bacayon, Jennifer Kumar, Asha Kwok, Jasmin Ullah, Jahanara Roth, Alan Chen, Daniel Crupi, Robert Schwartz, Joseph TI Dimensions of Perceived Racism and Self-Reported Health: Examination of Racial/Ethnic Differences and Potential Mediators SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE Racism; Ethnic discrimination; Self-reported health; Health; Social exclusion; Meditation; Depression ID MEXICAN-ORIGIN ADULTS; AFRICAN-AMERICAN ADULTS; MEDLEY HOSTILITY SCALE; PHYSICAL HEALTH; ETHNIC DISCRIMINATION; COMMUNITY SAMPLE; RESIDENTIAL SEGREGATION; COLLEGE-STUDENTS; WHITE AMERICANS; BLOOD-PRESSURE AB Background Many details of the negative relationship between perceived racial/ethnic discrimination and health are poorly understood. Purpose The purpose of this study was to examine racial/ethnic differences in the relationship between perceived discrimination and self-reported health, identify dimensions of discrimination that drive this relationship, and explore psychological mediators. Methods Asian, Black, and Latino(a) adults (N = 734) completed measures of perceived racial/ethnic discrimination, self-reported health, depression, anxiety, and cynical hostility. Results The association between perceived discrimination and poor self-reported health was significant and did not differ across racial/ethnic subgroups. Race-related social exclusion and threat/harassment uniquely contributed to poor health for all groups. Depression, anxiety, and cynical hostility fully mediated the effect of social exclusion on health, but did not fully explain the effect of threat. Conclusions Our results suggest that noxious effects of race-related exclusion and threat transcend between-group differences in discriminatory experiences. The effects of race-related exclusion and threat on health, however, may operate through different mechanisms. C1 [Brondolo, Elizabeth; Jhalani, Juhee; Pencille, Melissa; Atencio-Bacayon, Jennifer; Kumar, Asha; Kwok, Jasmin; Ullah, Jahanara] St Johns Univ, Dept Psychol, Jamaica, NY 11439 USA. [Hausmann, Leslie R. M.] Vet Affairs Pittsburgh Hlth Care Syst, Hlth Serv Res & Dev Serv, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Roth, Alan] Jamaica Hosp Med Ctr, Jamaica, NY USA. [Chen, Daniel; Crupi, Robert] Flushing Hosp Med Ctr, Flushing, NY USA. [Schwartz, Joseph] SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. RP Brondolo, E (reprint author), St Johns Univ, Dept Psychol, Jamaica, NY 11439 USA. EM brondole@stjohns.edu OI Brondolo, Elizabeth/0000-0002-7110-956X FU NHLBI NIH HHS [R01 HL065890, R01 HL068590, R01 HL068590-01A1] NR 100 TC 47 Z9 47 U1 1 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD AUG PY 2011 VL 42 IS 1 BP 14 EP 28 DI 10.1007/s12160-011-9265-1 PG 15 WC Psychology, Multidisciplinary SC Psychology GA 794UK UT WOS:000292926600002 PM 21374099 ER PT J AU Gault, CR Obeid, LM AF Gault, Christopher R. Obeid, Lina M. TI Still benched on its way to the bedside: sphingosine kinase 1 as an emerging target in cancer chemotherapy SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE Sphingolipids; sphingosine-1-phosphate; ceramide; chemoresistance; angiogenesis; oncogene ID PROTEIN-COUPLED RECEPTOR; HUMAN COLON-CANCER; SPHINGOLIPID METABOLISM; CELL-DEATH; ENDOTHELIAL-CELLS; PROSTATE-CANCER; BREAST-CANCER; SPHINGOSINE-1-PHOSPHATE LYASE; VASCULAR MATURATION; DEPENDENT MECHANISM AB For several decades, lipid biologists have investigated how sphingolipids contribute to physiology, cell biology, and cell fate. Foremost among these discoveries is the finding that the bioactive sphingolipids ceramide, sphingosine, and sphingosine-1-phosphate (S1P) have diverse and often opposing effects on cell fate. Interestingly, these bioactive sphingolipids can be interconverted by just a few enzymatic reactions. Therefore, much attention has been paid to the enzymes which govern these reactions with a disproportionate amount of focus on the enzyme sphingosine kinase 1 (SK1). Several studies have found that tissue expression of SK1 correlates with cancer stage, chemotherapy response, and tumor aggressiveness. In addition, overexpression of SK1 in multiple cancer cell lines increases their resistance to chemotherapy, promotes proliferation, allows for anchorage independent growth, and increases local angiogenesis. Inhibition of SK1 using either pharmacological inhibitors or by crossing SK1 null mice has shown promise in many xenograft models of cancer, as well as several genetic and chemically induced mouse models of carcinogenesis. Here, we review the majority of the evidence that suggests SK1 is a promising target for the prevention and/or treatment of various cancers. Also, we strongly advocate for further research into basic mechanisms of bioactive sphingolipid signaling, and an increased focus on the efficacy of SK inhibitors in non-xenograft models of cancer progression. C1 [Obeid, Lina M.] Med Univ S Carolina, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm, Charleston, SC USA. [Obeid, Lina M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med, 114 Doughty St,MSC 779, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NIH [R01AG16583, GM062887, P01 CA097132, NIH NRSA 5F3-HL093991]; VA MERIT Award [BX000156-01A1] FX This work was supported in part by: NIH grants R01AG16583, GM062887, and P01 CA097132 (LMO); NIH NRSA 5F3-HL093991 (CRG). VA MERIT Award BX000156-01A1 (LMO). NR 80 TC 17 Z9 20 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1040-9238 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PD AUG PY 2011 VL 46 IS 4 BP 342 EP 351 DI 10.3109/10409238.2011.597737 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 797JQ UT WOS:000293121100006 PM 21787121 ER PT J AU Nelson, K Taylor, L Lurie, N Escarce, J McFarland, L Fihn, SD AF Nelson, Karin Taylor, Leslie Lurie, Nicole Escarce, Jose McFarland, Lynne Fihn, Stephan D. TI Neighborhood Environment and Health Status and Mortality Among Veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE neighborhood; veterans; health status ID SOCIOECONOMIC-STATUS; OLDER-ADULTS; WALKABILITY; DATABASES; WALKING; PRIMER; DEATH AB BACKGROUND: The VHA is the largest integrated US health system and is increasingly moving care into the communities where veterans reside. Veterans who utilize the VA for their care have worse health status than the general population. However, there is limited evidence about the association of neighborhood environment and health outcomes among veterans. OBJECTIVES: The primary aim of this study is to assess the relative contribution of neighborhood environment, health system, and individual characteristics to health status and mortality of veterans. METHODS: Information on personal socio-economic indicators, existing medical conditions and health status were obtained from baseline data from a multi-site, randomized trial of primary care patients (n = 15,889). The physical component scale (PCS) and mental component scale (MCS) summarized health status. Census tracts were used as proxies for neighborhoods. A summary score based on census tract data characterized the neighborhood socio-economic environment and walkability. Data were analyzed with multilevel hierarchical models. Analyses of health status were cross-sectional. Mortality analyses were longitudinal as participants were followed for an average of 722.5 days to ascertain vital status. RESULTS: Neighborhood SES was associated with PCS and MCS scores, controlling for individual socio-economic status, self-reported co-morbid disease, smoking status, and health care access. In the lowest versus highest quartiles of neighborhood SES, adjusted PCS scores were 34.4 vs. 35.4 (p < 0.05) and adjusted MCS scores were 46.2 versus 47.0 (p < 0.05). PCS score was also significantly associated with neighborhood walkability (p < 0.05). Mortality was lower for veterans living in neighborhoods with the highest decile neighborhood SES (HR 0.78, highest vs. lowest decile 95% CI 0.63, 0.97). CONCLUSIONS: Veterans living in lower SES neighborhoods have poorer health status and a higher risk of mortality, independent of individual characteristics and health care access. Neighborhood walkability was associated with higher PCS scores. C1 [Nelson, Karin; Taylor, Leslie; Fihn, Stephan D.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Nelson, Karin; Fihn, Stephan D.] VA Puget Sound Hlth Care Syst, Gen Med Serv, Seattle, WA 98108 USA. [Nelson, Karin; McFarland, Lynne; Fihn, Stephan D.] Univ Washington, Dept Med, Seattle, WA USA. [Nelson, Karin] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. [Lurie, Nicole] US Dept Hlth & Human Serv, Washington, DC USA. [Escarce, Jose] RAND Hlth, Santa Monica, CA USA. RP Nelson, K (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98108 USA. EM Karin.Nelson@va.gov FU U.S. Department of Veterans Affairs, Office of Research and Development [IIR 04-436-3]; Seattle Epidemiologic Research and Information Center FX This material is based upon work supported by the U.S. Department of Veterans Affairs, Office of Research and Development VA Health Services Research and Development Program (IIR 04-436-3) and the Seattle Epidemiologic Research and Information Center. This work was presented at the Society for General Internal Medicine National Meeting (May, 2009) and at the VA HSR&D National Meeting (February, 2009). The views expressed in this article are those of the author and do not necessarily represent the views of the Department of Veterans Affairs. NR 40 TC 6 Z9 6 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2011 VL 26 IS 8 BP 862 EP 867 DI 10.1007/s11606-011-1710-0 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 794IO UT WOS:000292889000013 PM 21499826 ER PT J AU Rhodes, KV Kothari, CL Dichter, M Cerulli, C Wiley, J Marcus, S AF Rhodes, Karin V. Kothari, Catherine L. Dichter, Melissa Cerulli, Catherine Wiley, James Marcus, Steve TI Intimate Partner Violence Identification and Response: Time for a Change in Strategy SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE intimate partner violence; police incidents; health care screening; risk identification; interventions; emergency departments ID DOMESTIC VIOLENCE; PRIMARY-CARE; ALCOHOL INTERVENTIONS; WOMEN; EMERGENCY; EXPERIENCES; VICTIMS; INJURY; ABUSE; TRIAL AB BACKGROUND: While victims of intimate partner violence (IPV) present to health care settings for a variety of complaints; rates and predictors of case identification and intervention are unknown. OBJECTIVE: Examine emergency department (ED) case finding and response within a known population of abused women. DESIGN: Retrospective longitudinal cohort study. SUBJECTS: Police-involved female victims of IPV in a semi-rural Midwestern county. MAIN MEASURES: We linked police, prosecutor, and medical record data to examine characteristics of ED identification and response from 1999-2002; bivariate analyses and logistic regression analyses accounted for the nesting of subjects' with multiple visits. RESULTS: IPV victims (N = 993) generated 3,426 IPV-related police incidents (mean 3.61, median 3, range 1-17) over the 4-year study period; 785 (79%) generated 4,306 ED visits (mean 7.17, median 5, range 1-87), which occurred after the date of a documented IPV assault. Only 384 (9%) ED visits occurred within a week of a police-reported IPV incident. IPV identification in the ED was associated with higher violence severity, being childless and underinsured, more police incidents (mean: 4.2 vs 3.3), and more ED visits (mean: 10.6 vs 5.5) over the 4 years. The majority of ED visits occurring after a documented IPV incident were for medical complaints (3,378, 78.4%), and 72% of this cohort were never identified as victims of abuse. IPV identification was associated with the day of a police incident, transportation by police, self-disclosure of "domestic assault," and chart documentation of mental health and substance abuse issues. When IPV was identified, ED staff provided legally useful documentation (86%), police contact (50%), and social worker involvement (45%), but only assessed safety in 33% of the women and referred them to victim services 25% of the time. CONCLUSION: The majority of police-identified IPV victims frequently use the ED for health care, but are unlikely to be identified or receive any intervention in that setting. C1 [Rhodes, Karin V.] Univ Penn, Schools Med & Social Policy & Practice, Dept Emergency Med, Div Emergency Care Policy Res, Philadelphia, PA 19104 USA. [Kothari, Catherine L.] Michigan State Univ, Kalamazoo Ctr Med Studies, Kalamazoo, MI USA. [Dichter, Melissa] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Cerulli, Catherine] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Wiley, James] San Francisco State Univ, Publ Res Inst, San Francisco, CA 94132 USA. [Marcus, Steve] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Rhodes, KV (reprint author), Univ Penn, Schools Med & Social Policy & Practice, Dept Emergency Med, Div Emergency Care Policy Res, Philadelphia, PA 19104 USA. EM kvr@sp2.upenn.edu OI Kothari, Catherine/0000-0001-8072-8920 FU CDC [U17/CCU551067]; National Institute of Justice [NIJ 2006-WG-BX-0007]; NIMH [K23 MH64572, K01MH75965-01]; Center for Health Equity Research and Promotion, Philadelphia VA Medical Center FX The authors wish to thank Patricia Smith, Director, Violence Against Women Prevention Program, Michigan Department of Community Health; the Kalamazoo County Prosecutor's Office, all members of the Community Advisory Board, the YWCA Domestic Violence Program, and the many research assistants who worked on this project. This project builds on data collected for the MEDCIIN Projects under the CDC cooperative agreement U17/CCU551067.; None disclosed. Research support was primarily provided by a grant from the National Institute of Justice: NIJ 2006-WG-BX-0007; additional support for investigator time was provided by NIMH K23 MH64572 (Rhodes) and K01MH75965-01 (Cerulli) and the Center for Health Equity Research and Promotion, Philadelphia VA Medical Center (Dichter). Opinions or points of view expressed are those of the author(s) and do not necessarily reflect the official position or policies of the U.S. Department of Justice the Department of Veterans Affairs or the United States Government. NR 35 TC 20 Z9 20 U1 5 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2011 VL 26 IS 8 BP 894 EP 899 DI 10.1007/s11606-011-1662-4 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 794IO UT WOS:000292889000018 PM 21404130 ER PT J AU Goenka, R Barnett, LG Silver, JS O'Neill, PJ Hunter, CA Cancro, MP Laufer, TM AF Goenka, Radhika Barnett, Lisa G. Silver, Jonathan S. O'Neill, Patrick J. Hunter, Christopher A. Cancro, Michael P. Laufer, Terri M. TI Cutting Edge: Dendritic Cell-Restricted Antigen Presentation Initiates the Follicular Helper T Cell Program but Cannot Complete Ultimate Effector Differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CXC CHEMOKINE RECEPTOR-5; PLASMA-CELLS; B-CELLS; EXPRESSION; RESPONSES; IL-21; BCL6; ACTIVATION; FOLLICLES; BLIMP-1 AB Follicular helper T (TFH) cells are critical for germinal center ( GC) formation. The processes that drive their generation and effector potential remain unclear. In this study, we define requirements for MHC class II APCs in murine TFH cell formation by either transiently ablating or restricting Ag presentation to dendritic cells (DCs). We find that cognate interactions with DCs are necessary and sufficient to prime CD4(+) T cells toward a CXCR5(+)ICOS(+)Bcl6(+) T-FH cell intermediate. However, in the absence of additional APCs, these TFH cells fail to produce IL-21. Furthermore, in vitro priming of naive T cells by B cells engenders optimal production of IL-21, which induces a GC B cell transcriptional profile. These results support a multistep model for effector TFH cell priming and GC initiation, in which DCs are necessary and sufficient to induce a TFH cell intermediate that requires additional interactions with distinct APCs for full effector function. The Journal of Immunology, 2011, 187: 1091-1095. C1 [Laufer, Terri M.] Univ Penn Sch Med, BRB 2 3 753, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Barnett, Lisa G.] Univ Penn Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Silver, Jonathan S.; Hunter, Christopher A.; Laufer, Terri M.] Univ Penn Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. [Laufer, Terri M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Laufer, TM (reprint author), Univ Penn Sch Med, BRB 2 3 753, Dept Pathol & Lab Med, 421 Curie Blvd, Philadelphia, PA 19104 USA. EM cancro@mail.med.upenn.edu; tlaufer@mail.med.upenn.edu FU Veterans Administration Merit Award [BX000435]; National Institutes of Health [R01 AI 42334, R01 AI 073939, T32 AI 055428, T32 AI 007532] FX This work was supported by Veterans Administration Merit Award BX000435 (to T. M. L.), National Institutes of Health Grants R01 AI 42334 (to C. A. H.), and R01 AI 073939 (to M.P.C.). R.G. was supported by National Institutes of Health Training Grant T32 AI 055428. J.S.S. is supported by National Institutes of Health Training Grant T32 AI 007532. NR 26 TC 101 Z9 104 U1 0 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 AUG 1 PY 2011 VL 187 IS 3 BP 1091 EP 1095 DI 10.4049/jimmunol.1100853 PG 5 WC Immunology SC Immunology GA 794CY UT WOS:000292874200006 PM 21715693 ER PT J AU Freed, KA Blangero, J Howard, T Johnson, MP Curran, JE Garcia, YR Lan, HC Abboud, HE Moses, EK AF Freed, Katy A. Blangero, John Howard, Tom Johnson, Matthew P. Curran, Joanne E. Garcia, Yvonne R. Lan, Hao-Chang Abboud, Hanna E. Moses, Eric K. TI The 57 kb deletion in cystinosis patients extends into TRPV1 causing dysregulation of transcription in peripheral blood mononuclear cells SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID NEPHROPATHIC CYSTINOSIS; CTNS MUTATIONS; GENE; MICE; CAPSAICIN; RECEPTOR AB Background Cystinosis is an autosomal recessive disease characterised by the abnormal accumulation of lysosomal cystine. Mutations in the cystinosin gene (CTNS) represent known causes for the disease. The major cystinosis mutation is a 57 kb deletion on human chromosome 17p13 that removes the majority of CTNS and the entire adjacent gene, CARKL/SHPK. Objectives In order to identify other genes that may influence the cystinosis pathobiological pathway, peripheral blood mononuclear cells (PBMC) were collected from cystinosis family members, and DNA and RNA extracted. Results Using whole genome transcriptional profiling, transient receptor potential vanilloid 1 (TRPV1) was found to be differentially expressed in association with cystinosis. This was verified using TaqMan qRT-PCR. There was a 72% reduction in PBMC TRPV1 mRNA levels in cystinosis individuals homozygous for the 57 kb deletion (n = 6) compared to unaffected individuals without the deletion (n = 6) (p = 0.002). TRPV1 is a sensory receptor located on chromosome 17p13, adjacent to CARKL/SHPK. It was ascertained that the 57 kb deletion extends from exon 10 of CTNS, upstream through CARKL/SHPK, to intron 2 of TRPV1, thus deleting the first two non-coding exons. Conclusion This is the first study to report that the 57 kb deletion extends into the TRPV1 gene causing dysregulation of transcription in PBMC isolated from cystinosis patients. C1 [Freed, Katy A.; Blangero, John; Johnson, Matthew P.; Curran, Joanne E.; Garcia, Yvonne R.; Lan, Hao-Chang; Moses, Eric K.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX 78245 USA. [Howard, Tom] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. [Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Freed, KA (reprint author), Texas Biomed Res Inst, Dept Genet, POB 760549, San Antonio, TX 78245 USA. EM kfreed@txbiomedgenetics.org FU Cystinosis Research Foundation; National Center for Research Resources, National Institutes of Health [C06 RR017515]; Azar familiy of San Antonio; Shepperd family of San Antonio FX Financial support for this project has been generously provided by the Cystinosis Research Foundation and the Azar and Shepperd families of San Antonio. This investigation was conducted in facilities constructed with support from Research Facilities Improvement Program grants C06 RR017515 from the National Center for Research Resources, National Institutes of Health. There was no involvement in the study design, analysis or interpretation of the data by these funding sources. Cystinosis Research Foundation 18802 Bardeen AvenueIrvine, CA 92612. NR 20 TC 8 Z9 8 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD AUG PY 2011 VL 48 IS 8 BP 563 EP 566 DI 10.1136/jmg.2010.083303 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 795FK UT WOS:000292958800011 PM 21546516 ER PT J AU Yukl, SA Li, PL Fujimoto, K Lampiris, H Lu, CYM Hare, CB Deeks, SG Liegler, T Pandori, M Havlir, DV Wong, JK AF Yukl, Steven A. Li, Peilin Fujimoto, Katsuya Lampiris, Harry Lu, Chuanyi M. Hare, C. Bradley Deeks, Steven G. Liegler, Teri Pandori, Mark Havlir, Diane V. Wong, Joseph K. TI Modification of the Abbott RealTime assay for detection of HIV-1 plasma RNA viral loads less than one copy per milliliter SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HIV; Plasma RNA; Viral load; Single copy; Abbott ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE-CHAIN-REACTION; SUPPRESSIVE ANTIRETROVIRAL THERAPY; LOW-LEVEL VIREMIA; TYPE-1 RNA; INFECTED INDIVIDUALS; RESIDUAL VIREMIA; CLINICAL SPECIMENS; IMMUNE ACTIVATION; DNA-SEQUENCES AB Although commercial tests are approved for detection of HIV-1 plasma viral loads >= 20 copies per milliliter (ml), only one specialized research assay has been reported to detect plasma viral loads as low as 1 copy/ml. This manuscript describes a method of concentrating HIV-1 virions from up to 30 ml of plasma, which can be combined with a commercial viral load test to create a widely available, reproducible assay for quantifying plasma HIV RNA levels less than 1 copy/ml. Using this pre-analytically modified assay, samples with a known level of 0.5 copy/ml were detected in 8 of 12 replicates (mean 0.47 copy/ml; 95% confidence interval (CI) 0.14-0.81 copy/ml) and samples with a known level of 1.0 copy/ml were detected in 13 of 13 replicates (mean 1.96 copy/ml; 95% CI 1.42-2.50 copy/ml). By concentrating virus from 30 ml of plasma, HIV RNA could be measured in 16 of 19 samples (84%) from 12 of 12 subjects (mean 2.77 copy/ml; 95% CI 0.86-4.68 copy/ml). The measured viral load correlated inversely (r = -0.78; p = 0.028) with the total duration of viral suppression (viral load < 40 copies/ml). (C) 2011 Elsevier B.V. All rights reserved. C1 [Yukl, Steven A.; Li, Peilin; Fujimoto, Katsuya; Lampiris, Harry; Lu, Chuanyi M.; Wong, Joseph K.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Yukl, Steven A.; Lampiris, Harry; Lu, Chuanyi M.; Hare, C. Bradley; Deeks, Steven G.; Liegler, Teri; Havlir, Diane V.; Wong, Joseph K.] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94143 USA. [Hare, C. Bradley; Deeks, Steven G.; Liegler, Teri; Havlir, Diane V.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Pandori, Mark] Dept Publ Hlth, San Francisco, CA 94102 USA. RP Yukl, SA (reprint author), 4150 Clement St,111W3, San Francisco, CA 94121 USA. EM steven.yukl@ucsf.edu; peilin.li@va.gov; kfujimo@abelia.ocn.ne.jp; harry.lampiris@va.gov; Mark.lu@va.gov; Chare@php.ucsf.edu; Sdeeks@php.ucsf.edu; TLiegler@sfgh.ucsf.edu; Mark.Pandori@sfdph.org; havlir@php.ucsf.edu; joseph.wong@ucsf.edu RI Fujimoto, Katsuya/G-2835-2012 FU U.S. Department of Veterans Affairs; National Institute of Health [1K23AI089397, P30-AI027763, NS051145, T32 AI60530] FX The authors thank the following people and institutions: (1) the study participants; (2) the study nurses at the San Francisco VA ID Clinic (Sandra Charles and Linda Adams); (3) the PLUS study staff; and (4) the staff at the San Francisco Department of Public Health. This work was supported in part by the U.S. Department of Veterans Affairs (VA Merit Award [JW/SY]) and the National Institute of Health (NIH grants 1K23AI089397 (SY), P30-AI027763 (SY, JW, TL), NS051145 [JW/SY], and T32 AI60530 [DH/SY]). NR 49 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD AUG PY 2011 VL 175 IS 2 BP 261 EP 265 DI 10.1016/j.jviromet.2011.04.015 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 793BF UT WOS:000292794700017 PM 21536073 ER PT J AU Amari, W Zeringue, AL McDonald, JR Caplan, L Eisen, SA Ranganathan, P AF Amari, Wassila Zeringue, Angelique L. McDonald, Jay R. Caplan, Liron Eisen, Seth A. Ranganathan, Prabha TI Risk of non-melanoma skin cancer in a national cohort of veterans with rheumatoid arthritis SO RHEUMATOLOGY LA English DT Article DE Non-melanoma skin cancer; Non-biologic; TNF antagonist; DMARDs; Rheumatoid arthritis ID TUMOR-NECROSIS-FACTOR; CHRONIC LYMPHOCYTIC-LEUKEMIA; ADMINISTRATIVE DATA; FACTOR-ALPHA; MALIGNANCY; THERAPY; LYMPHOMA; MELANOMA; TRANSPLANTATION; METHOTREXATE AB Methods. We examined skin cancer risk in a cohort of 20 648 patients with RA derived from the Department of Veterans' Affairs (VA) national administrative databases. The cohort was divided into two medication groups: patients treated with non-biologic and TNF-alpha antagonist DMARDs. We defined skin cancer as the first occurrence of an International Classification of Disease, Version 9, Clinical Modification (ICD-9-CM) code for NMSC after initiation of a DMARD. Outcome risk was described using hazard ratios (HRs) with Cox proportional hazards regression for time-to-event analysis and logistic regression. We performed medical record review to validate the diagnosis of NMSC. Results. Incidence of NMSC was 18.9 and 12.7 per 1000 patient-years in patients on TNF-alpha antagonists and non-biologic DMARDs, respectively. Patients on TNF-alpha antagonists had a higher risk of developing NMSC (HR 1.42; 95% CI 1.24, 1.63). Risk factors for NMSC included older age, male gender, NSAID and glucocorticoid use and a history of prior malignancies. There was substantial agreement between ICD-9-CM diagnosis of NMSC and medical record validation (kappa = 0.61). Conclusion. TNF-alpha antagonist therapy in veterans with RA may be associated with an increased risk of NMSC, compared with therapy with non-biologic DMARDs. Rheumatologists should carefully screen patients receiving TNF-alpha antagonists for pre-cancerous skin lesions and skin cancer. C1 [Ranganathan, Prabha] Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63110 USA. [Zeringue, Angelique L.; McDonald, Jay R.; Eisen, Seth A.] St Louis Vet Affairs Med Ctr, Dept Med, St Louis, MO USA. [Caplan, Liron] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. [Caplan, Liron] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. RP Ranganathan, P (reprint author), Washington Univ, Sch Med, Dept Med, Div Rheumatol, 660 S Euclid Ave,Campus Box 8045, St Louis, MO 63110 USA. EM prangana@dom.wustl.edu RI Zeringue, Angelique/I-1755-2012 FU US Department of Veterans Affairs, Veterans Health Administration Health Services Research and Development Service [IAF 06-026] FX US Department of Veterans Affairs, Veterans Health Administration Health Services Research and Development Service project IAF 06-026. The views expressed in this article do not necessarily represent the views of the Department of Veterans Affairs. NR 45 TC 39 Z9 39 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD AUG PY 2011 VL 50 IS 8 BP 1431 EP 1439 DI 10.1093/rheumatology/ker113 PG 9 WC Rheumatology SC Rheumatology GA 793OD UT WOS:000292832100014 PM 21415022 ER PT J AU Rooney, T Scherzer, R Shigenaga, JK Graf, J Imboden, JB Grunfeld, C AF Rooney, Terence Scherzer, Rebecca Shigenaga, Judy K. Graf, Jonathan Imboden, John B. Grunfeld, Carl TI Levels of plasma fibrinogen are elevated in well-controlled rheumatoid arthritis SO RHEUMATOLOGY LA English DT Article DE Rheumatoid arthritis; Fibrinogen; Cardiovascular risk; 28-joint DAS; Clinical disease activity index; Simplified disease activity index; ESR; CRP; Serum amyloid A; IL-6 ID C-REACTIVE PROTEIN; ERYTHROCYTE SEDIMENTATION-RATE; CARDIOVASCULAR RISK-FACTORS; CORONARY-HEART-DISEASE; ACTIVITY SCORE; INFLAMMATION; RECOMMENDATIONS; ASSOCIATION; MORTALITY; MARKERS AB Methods. Patients with RA and controls were recruited at the University of California, San Francisco (UCSF). Disease activity was evaluated using standard composite indices. Fibrinogen, ESR, serum CRP, acute-phase serum amyloid A and levels of selected cytokines were quantified. Results. A total of 105 RA patients and 62 controls were studied. Among patients with RA, disease activity ranged from quiescent to highly active disease. Circulating fibrinogen levels were significantly higher in RA than in controls [median (interquartile range) 466 (391-575) vs 367 (309-419) mg/dl, respectively, P < 0.0001]. This difference remained highly statistically significant after adjustment for demographic variables and BMI. Although fibrinogen correlated significantly with clinical measures of disease activity, significantly elevated levels were observed at low levels of activity, even in RA patients with no detectable swollen or tender joints. In multivariable models, similar to 80% of the increased fibrinogen in RA was accounted for by increases in CRP and ESR. Conclusion. Circulating levels of fibrinogen are elevated in RA and correlated with markers of inflammation, but only modestly correlate with clinical assessments of disease activity. Even RA patients with excellent clinical disease control exhibit elevated levels compared with controls. C1 [Rooney, Terence] Univ Calif San Francisco, VA Med Ctr, Div Rheumatol, San Francisco, CA 94121 USA. [Scherzer, Rebecca; Shigenaga, Judy K.; Grunfeld, Carl] Univ Calif San Francisco, VA Med Ctr, Div Endocrinol & Metab, Dept Med, San Francisco, CA 94121 USA. [Graf, Jonathan; Imboden, John B.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Rheumatol, Dept Med, San Francisco, CA 94121 USA. RP Grunfeld, C (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Metab Sect, 111F,4150 Clement St, San Francisco, CA 94121 USA. EM carl.grunfeld@ucsf.edu FU ACR; Rosalind Russell Arthritis Research Center; Albert L. and Janet A. Schultz Supporting Foundation; Hellman Family Award for Early-Career Faculty at the UCSF FX This work was supported by an ACR Within our Reach Grant for RA, the Rosalind Russell Arthritis Research Center, the Albert L. and Janet A. Schultz Supporting Foundation, and a Hellman Family Award for Early-Career Faculty at the UCSF; and with resources and the use of facilities of the Veterans Affairs Medical Centers in San Francisco. NR 39 TC 7 Z9 8 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD AUG PY 2011 VL 50 IS 8 BP 1458 EP 1465 DI 10.1093/rheumatology/ker011 PG 8 WC Rheumatology SC Rheumatology GA 793OD UT WOS:000292832100018 PM 21441551 ER PT J AU Verellen, RM Cavazos, JE AF Verellen, Rebecca M. Cavazos, Jose E. TI Pathophysiological Considerations of Seizures, Epilepsy, and Status Epilepticus in the Elderly SO AGING AND DISEASE LA English DT Review DE Elderly; Seizures; Epilepsy; Status; Aging; Pathophysiology AB Acute seizures, epilepsy and status epilepticus have the highest incidences in those over the age of 60 as compared to all other age groups. The most common etiological factors for epilepsy in the elderly are related to cerebrovascular disease. Diagnosing epilepsy in the elderly is challenging because of the subtle manifestations of partial seizures and the presence of age related cognitive difficulties, co-morbid conditions, and medications. Epilepsy treatment in this population is also difficult due to age related changes in pharmacokinetics and pharmacodynamics as well as individual variability. There are considerable gaps of knowledge about the basic pathophysiological mechanisms of recurrent partial onset seizures in the aged brain. This article critically reviews pathophysiological considerations that might impact the scientific approach of experimental research modeling of unprovoked seizures and epilepsy in elderly individuals, and the limited experimental epilepsy research on aged models. C1 [Verellen, Rebecca M.; Cavazos, Jose E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. [Cavazos, Jose E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Cavazos, Jose E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Cavazos, Jose E.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio VA Epilepsy Ctr Excellence, San Antonio, TX 78229 USA. RP Cavazos, JE (reprint author), 8300 Floyd Curl Dr,MC 7883, San Antonio, TX 78229 USA. EM cavazosj@uthscsa.edu RI Cavazos, Jose/J-4122-2016 OI Cavazos, Jose/0000-0001-5777-2608 NR 58 TC 10 Z9 12 U1 0 U2 2 PU INT SOC AGING & DISEASE PI FORT WORTH PA EDITORIAL OFF, 3400 CAMP BOWIE BLVD, FORT WORTH, TX 76106 USA SN 2152-5250 J9 AGING DIS JI Aging Dis. PD AUG PY 2011 VL 2 IS 4 BP 278 EP 285 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA V32KP UT WOS:000208950400002 PM 22396879 ER PT J AU Anand, IS Rector, TS Cleland, JG Kckelvie, RS Persson, H Mcmurray, JJ Zile, M Komajda, M Massie, B Carson, P AF Anand, I. S. Rector, T. S. Cleland, J. G. Kckelvie, R. S. Persson, H. Mcmurray, J. J. Zile, M. Komajda, M. Massie, B. Carson, P. TI Prognostic value of baseline NT-proBNP and its interactions with irbesartan treatment in patients with heart failure and preserved ejection fraction: Findings from the I-PRESERVE trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Anand, I. S.; Rector, T. S.] Univ Minnesota, Minneapolis, MN USA. [Cleland, J. G.] Univ Hull, Castle Hill Hosp, Kingston Upon Hull, Yorks, England. [Kckelvie, R. S.] Populat Hlth Res Inst, Hamilton, ON, Canada. [Persson, H.] Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden. [Mcmurray, J. J.] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Zile, M.] Med Univ S Carolina, Charleston, SC USA. [Zile, M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Komajda, M.] Hosp Pitie Salpetriere, AP HP, Paris, France. [Massie, B.] Univ Calif San Francisco, Vet Adm Med Ctr, Cardiol Sect, San Francisco, CA USA. [Carson, P.] Vet Affairs Med Ctr, Washington, DC 20422 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2011 VL 32 SU 1 BP 495 EP 495 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TI UT WOS:000208702704079 ER PT J AU Ataya, B Tzeng, E Zuckerbraun, BS AF Ataya, Bilal Tzeng, Edith Zuckerbraun, Brian S. TI Nitrite-Generated Nitric Oxide to Protect Against Intimal Hyperplasia Formation SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID BLOOD-PRESSURE; L-ARGININE; MOLECULAR-MECHANISMS; DIETARY NITRATE; BIOLOGY; ENDOTHELIUM; PATHWAY; DISEASE; NO; PATHOPHYSIOLOGY AB Vascular disease is a leading cause of morbidity and mortality worldwide. Current vascular therapeutic interventions directed at diseased vessels are restricted in long-term efficacy by the development of intimal hyperplasia and the reformation of flow-limiting disease. The vascular injury and inflammation that ensues from the intervention, especially in the setting of an existing atherosclerotic vascular disease, results in further endothelial dysfunction and subsequent smooth muscle cell proliferation and migration. Although the etiology of intimal hyperplasia is multifactorial, impaired nitric oxide (NO) signaling has been implicated. The vasoprotective properties of NO have been intensely studied, and many investigations have focused on harnessing this biological system for therapeutic benefit. Continued studies investigate the role of impaired NO signaling via the classical arginine/NO synthase (NOS)/NO pathway in the setting of intimal hyperplasia. Furthermore, the possible protective effects of nitrate and nitrite-generated NO via non-NOS-mediated pathways to limit vascular injury have been recently appreciated and will likely prove to be an important vasoregulatory and vasoprotective signaling pathway. (Trends Cardiovasc Med 2011;21:157-162) (C) 2011 Published by Elsevier Inc. C1 [Ataya, Bilal; Tzeng, Edith; Zuckerbraun, Brian S.] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Tzeng, Edith; Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Zuckerbraun, BS (reprint author), Univ Pittsburgh, 200 Lothrop St,F1200 PUH, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu NR 40 TC 11 Z9 12 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD AUG PY 2011 VL 21 IS 6 BP 157 EP 162 AR PII S1050-1738(12)00113-2 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 981CI UT WOS:000306942700001 PM 22814422 ER PT J AU Bhattacharya, A Leonard, S Tardif, S Buffenstein, R Fischer, KE Richardson, A Austad, SN Chaudhuri, AR AF Bhattacharya, Arunabh Leonard, Shanique Tardif, Suzette Buffenstein, Rochelle Fischer, Kathleen E. Richardson, Arlan Austad, Steven N. Chaudhuri, Asish R. TI Attenuation of liver insoluble protein carbonyls: indicator of a longevity determinant? SO AGING CELL LA English DT Editorial Material DE naked mole-rat; marmoset; bats; protein carbonylation; dietary restriction; oxidative stress ID DIETARY RESTRICTION; OXIDATIVE DAMAGE; ANTIOXIDANT ENZYMES; LIFE-SPAN; DISEASE; RAT; METABOLISM; PROTEASOME; SENESCENCE; ANIMALS AB Oxidative damage affects protein structure and function. Progressive accumulation of oxidized proteins is considered a putative mechanism of aging; however, empirical evidence supporting their role in aging is inconsistent. This inconsistency may reflect a failure to distinguish damage to particular cellular compartments. We found a significant reduction of protein carbonyls in the insoluble, but not in the soluble, fraction of liver tissues of long-lived compared with their short-lived counterpart. Of cellular components analyzed, only nuclear protein carbonyl level was uniformly reduced in long-lived compared with short-lived animals. This observation suggests that attenuated accumulation of protein carbonyls in the nucleus, where they can affect multiple aspects of gene expression and DNA repair, might contribute to the longevity in mammalian species. C1 [Bhattacharya, Arunabh; Leonard, Shanique; Tardif, Suzette; Buffenstein, Rochelle; Fischer, Kathleen E.; Richardson, Arlan; Austad, Steven N.; Chaudhuri, Asish R.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Bhattacharya, Arunabh; Tardif, Suzette; Richardson, Arlan; Austad, Steven N.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Buffenstein, Rochelle; Fischer, Kathleen E.; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Fischer, Kathleen E.; Chaudhuri, Asish R.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Austad, Steven N.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Chaudhuri, Asish R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. RP Chaudhuri, AR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Texas Res Pk Campus,15355 Lambda Dr, San Antonio, TX 78245 USA. EM austad@uthscsa.edu; chaudhuria@uthscsa.edu FU NIA NIH HHS [AG-022891, K07 AG025063, K07 AG025063-04, AG022873, K07 AG02506304, R01 AG022873, R01 AG022891] NR 33 TC 10 Z9 10 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD AUG PY 2011 VL 10 IS 4 BP 720 EP 723 DI 10.1111/j.1474-9726.2011.00712.x PG 4 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 791FB UT WOS:000292648800015 PM 21463461 ER PT J AU Lockhart, SR Zimbeck, AJ Baddley, JW Marr, KA Andes, DR Walsh, TJ Kauffman, CA Kontoyiannis, DP Ito, JI Pappas, PG Chiller, T AF Lockhart, Shawn R. Zimbeck, Alicia J. Baddley, John W. Marr, Kieren A. Andes, David R. Walsh, Thomas J. Kauffman, Carol A. Kontoyiannis, Dimitrios P. Ito, James I. Pappas, Peter G. Chiller, Tom TI In Vitro Echinocandin Susceptibility of Aspergillus Isolates from Patients Enrolled in the Transplant-Associated Infection Surveillance Network SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; ANTIFUNGAL AGENTS; RECIPIENTS; ANIDULAFUNGIN; CASPOFUNGIN; TRANSNET AB We determined the echinocandin minimum effective concentration (MEC) values for caspofungin, micafungin, and anidulafungin against 288 Aspergillus isolates prospectively collected from transplant patients with proven or probable invasive aspergillosis between 2001 and 2006 as part of the Transplant-Associated Infection Surveillance Network (TRANSNET). We demonstrated that the vast majority of Aspergillus isolates had MEC values at or below the epidemiological cutoff values for caspofungin, micafungin, and anidulafungin, including those from patients who had received caspofungin. C1 [Lockhart, Shawn R.; Zimbeck, Alicia J.; Chiller, Tom] Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA 30333 USA. [Baddley, John W.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Dept Med, Infect Dis Sect, Birmingham, AL USA. [Marr, Kieren A.] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. [Andes, David R.] Univ Wisconsin, Dept Med, Div Infect Dis, Madison, WI USA. [Walsh, Thomas J.] Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA. [Walsh, Thomas J.] New York Presbyterian Hosp, New York, NY USA. [Walsh, Thomas J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Kauffman, Carol A.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Kauffman, Carol A.] Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Med, Houston, TX 77030 USA. [Ito, James I.] City Hope Natl Med Ctr, Dept Med, Div Infect Dis, Duarte, CA 91010 USA. [Pappas, Peter G.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. RP Lockhart, SR (reprint author), Ctr Dis Control & Prevent, Mycot Dis Branch, 1600 Clifton Rd,Mailstop G-11, Atlanta, GA 30333 USA. EM gyi2@cdc.gov FU Association of Public Health Laboratories (APHL); Astellas; Pfizer; Merck; Schering-Plough; Enzon FX A.J.Z. was supported by the Association of Public Health Laboratories (APHL). TRANSNET was sponsored by Astellas, Pfizer, Merck, and Schering-Plough. This work was funded by a grant from Merck. Potential conflicts of interest are as follows: P.G.P. receives research support and is an ad hoc advisor for Merck, Pfizer, and Astellas; J.W.B. received research grants from Merck, Astellas, and Pfizer and is a consultant/advisor for Merck and Pfizer; J.I.I. received honoraria for speakers' activities from Astellas, Cubist, Merck, and Pfizer and is a consultant for Sigma Tau; D.R.A. has received grants from and is a consultant for Merck, Astellas, and Pfizer; C.A.K. receives research support from Merck and chairs a data adjudication committee for Pfizer; K.A.M. received research grants from Merck, Astellas, and Pfizer and is on the advisory board or is consulting for Astellas, Basilea, Merck, and Pfizer; D.P.K. received research support and honoraria from Schering-Plough, Pfizer, Astellas, Enzon, and Merck; T.J.W. is in consultation with iCo, Vestagen, Trius, and Sigma Tau. All other authors have no potential conflicts. NR 17 TC 13 Z9 13 U1 0 U2 1 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 AUG PY 2011 VL 55 IS 8 BP 3944 EP 3946 DI 10.1128/AAC.00428-11 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 792HV UT WOS:000292733800040 PM 21670187 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Gambles of gastroenterology SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Article DE medical decision analysis; modeling; outcome research; probability theory; side-effects of medical interventions; threshold analysis AB Background Diagnostic and therapeutic procedures of gastroenterology can frequently tax a patient's health. In addition to the risk of side-effects such procedures may also reduce the patient's well-being. The probability of achieving cure depends on the interplay between the patient's initial health status and the expected efficacy of the gastroenterological interventions. Methods The mathematical concept of the 'gambler's ruin' from probability theory is used to model the interplay among the various factors affecting clinical outcome. Results The model illustrates in a quantitative manner how the physician's ultimate success in achieving cure depends on a given patient's initial health status, and the characteristics of the interventional procedures used. The analysis also illustrates that in some dire clinical situations, risking the patient's life in one single and bold step can yield a better overall outcome than trying to advance the patient's health by multiple small and cautious steps. Conclusion Using the gambler's ruin as a model for medical risk taking could contribute to medical teaching and promote the understanding of the some general principles that shape many clinical decisions in gastroenterology. Eur J Gastroenterol Hepatol 23: 651-655 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, 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 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 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD AUG PY 2011 VL 23 IS 8 BP 651 EP 655 DI 10.1097/MEG.0b013e328347afac PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 789GK UT WOS:000292503100003 PM 21623189 ER PT J AU Greenstein, RJ Cameron, W Brown, ST AF Greenstein, Robert J. Cameron, William Brown, Sheldon T. TI Considered "negative" for MAP, these results would be very "positive" for tuberculoid leprosy SO JOURNAL OF CROHNS & COLITIS LA English DT Letter ID MYCOBACTERIUM C1 [Greenstein, Robert J.; Brown, Sheldon T.] James J Peters VAMC, Dept Surg, Bronx, NY USA. [Cameron, William] Ottawa Hosp Res Inst, Div Infect Dis, Ottawa, ON, Canada. RP Greenstein, RJ (reprint author), James J Peters VAMC, Dept Surg, Bronx, NY USA. EM BGAxis@aol.com OI Cameron, Bill/0000-0002-0090-3539 NR 6 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-9946 J9 J CROHNS COLITIS JI J. Crohns Colitis PD AUG PY 2011 VL 5 IS 4 BP 373 EP 373 DI 10.1016/j.crohns.2011.03.013 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 792YJ UT WOS:000292786000015 PM 21683311 ER PT J AU Vance, D Larsen, KI Eagerton, G Wright, MA AF Vance, David Larsen, Kirsten I. Eagerton, Gregory Wright, Mary A. TI Comorbidities and Cognitive Functioning: Implications for Nursing Research and Practice SO JOURNAL OF NEUROSCIENCE NURSING LA English DT Article ID OLDER-ADULTS; DEPRESSIVE SYMPTOMS; ALZHEIMERS-DISEASE; BRAIN STRUCTURE; BLOOD-PRESSURE; PERFORMANCE; IMPAIRMENT; ASSOCIATION; MEMORY; HIV AB Optimal cognitive functioning is necessary to successfully negotiate one's environment, yet medical conditions can interfere with brain health, thus negatively impacting cognitive functioning. Such comorbidities include hypertension, heart disease, diabetes, depression, and HIV, as well as others. The physiological properties of these comorbidities can reduce one's cognitive reserve and limit one's cognitive efficiency. This article provides an overview of a few common comorbidities known to affect cognitive functioning and addresses ways in which cognitive functioning may be ameliorated and protected or mitigated in lieu of cognitive declines in such clinical populations. Implications for nursing practice and research are posited. C1 [Vance, David; Wright, Mary A.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA. [Larsen, Kirsten I.] Univ Alabama Birmingham, UAB Hosp, Birmingham, AL USA. [Eagerton, Gregory] Birmingham VA Med Ctr, Patient Nursing Serv, Birmingham, AL USA. RP Vance, D (reprint author), Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA. EM devance@uab.edu OI Vance, David/0000-0002-0498-6263 NR 51 TC 19 Z9 19 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0888-0395 J9 J NEUROSCI NURS JI J. Neurosci. Nurs. PD AUG PY 2011 VL 43 IS 4 BP 215 EP 224 DI 10.1097/JNN.0b013e3182212a04 PG 10 WC Clinical Neurology; Nursing SC Neurosciences & Neurology; Nursing GA 792QK UT WOS:000292763300008 PM 21796044 ER PT J AU Wulkersdorfer, B Kao, KK Agopian, VG Dunn, JC Wu, BM Stelzner, M AF Wulkersdorfer, Beatrix Kao, Kenneth K. Agopian, Vatche G. Dunn, James C. Wu, Ben M. Stelzner, Matthias TI Growth Factors Adsorbed on Polyglycolic Acid Mesh Augment Growth of Bioengineered Intestinal Neomucosa SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE tissue engineering; growth factors; scaffolds; Matrigel; small intestine; neomucosa ID GLUCAGON-LIKE PEPTIDE-2; SMALL-BOWEL RESECTION; STEM-CELL TRANSPLANTATION; ENGINEERED SMALL-INTESTINE; IN-VITRO; BASEMENT-MEMBRANE; EPITHELIAL-CELLS; TRANSFERRIN RECEPTOR; SGLT1 EXPRESSION; FACTOR RELEASE AB Production of tissue engineered small intestine (TESI) has been limited by the relatively large amount of native tissue required to generate neomucosa. The influence of growth factors and three-dimensional (3D) extracellular matrices on TESI has been studied both in vitro and in vivo, and positive growth effects on tissue mass and differentiation were noted. The present study investigates the impact of single doses of glucagon-like peptide-2 (GLP-2), hepatocyte growth factor (HGF), or holo-transferrin adsorbed onto a polyglycolic (PGA) mesh scaffold using a rat small-intestinal organoid transplant model. In Experiment I, intestinal organoids were seeded onto PGA mesh discs, suspended in either Matrigel (n = 8) or a vehicle control (n = 8), and implanted into syngenic recipients. In Experiment II, GLP-2 (n = 8), HGF (n = 8), or transferrin (n = 8) were adsorbed onto PGA mesh discs. Intestinal organoids were then suspended in Matrigel and seeded onto each growth factor-loaded PGA disc or onto control discs without growth factors (n = 12). In addition, organoids were suspended in vehicle and seeded onto control discs (n = 12). All discs were implanted into syngenic recipients. After 4 wk, histologic analysis of the samples revealed significantly greater neomucosal surface area (3.62 +/- 0.33 mm(2) versus 0.92 +/- 0.11 mm(2), P < 0.0001) and cyst diameter (2.83 +/- 0.14 mm versus 2.06 +/- 0.07 mm, P < 0.0001) in groups treated with Matrigel compared with vehicle controls. The addition of holo-transferrin to the scaffolds further augmented neomucosal surface area (9.11 +/- 0.66 mm(2) versus 3.01 +/- 0.22 mm(2), P < 0.01), whereas that of GLP-2 stimulated the formation of increased numbers of cysts (8.88 +/- 0.46 versus 4.18 +/- 0.25, P < 0.01). These data suggest that Matrigel and growth factors adsorbed to polymer scaffolds can be used to manipulate the morphology of TESI. Published by Elsevier Inc. C1 [Stelzner, Matthias] Univ Calif Los Angeles, Dept Surg, VA Greater Los Angeles, Hlth Care Syst, Los Angeles, CA 90073 USA. [Dunn, James C.; Wu, Ben M.] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90073 USA. RP Stelzner, M (reprint author), Univ Calif Los Angeles, Dept Surg, VA Greater Los Angeles, Hlth Care Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Matthias.Stelzner@va.gov NR 69 TC 8 Z9 8 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD AUG PY 2011 VL 169 IS 2 BP 169 EP 178 DI 10.1016/j.jss.2009.11.719 PG 10 WC Surgery SC Surgery GA 791BF UT WOS:000292634100009 PM 20444471 ER PT J AU Spurgeon, SE Pindyck, T Okada, C Chen, YY Chen, ZQ Mater, E Abbi, K Epner, EM AF Spurgeon, Stephen E. Pindyck, Talia Okada, Craig Chen, Yiyi Chen, Zunqiu Mater, Elana Abbi, Kamal Epner, Elliot M. TI Cladribine plus rituximab is an effective therapy for newly diagnosed mantle cell lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Article DE Mantle cell lymphoma; cladribine; rituximab; response ID INTERNATIONAL PROGNOSTIC INDEX; PROGRESSION-FREE SURVIVAL; CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; STUDY-GROUP GLSG; TERM-FOLLOW-UP; HAIRY-CELL; PHASE-II; 2-CHLORODEOXYADENOSINE; FLUDARABINE AB Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma that is incurable with standard chemotherapy. There is no consensus on the best initial therapy, especially for elderly patients, who are not candidates for aggressive treatment approaches. Current National Comprehensive Cancer Network (NCCN) treatment guidelines include rituximab (R) plus cladribine for the initial treatment of MCL. However, few data are available to substantiate this recommendation. Therefore, to further define the role of R-cladribine for the initial treatment of MCL, we performed a retrospective chart review of 31 patients with MCL (median age, 67) treated with R-cladribine. The majority of responding patients also received R maintenance. The overall response rate was 87%, with 61% of patients achieving a complete remission (CR/CRu). The estimated median follow-up was 32.5 months, median PFS was 37.5 months, and median OS was 85.2 months. One of 19 (5.3%) subjects in CR/CRu relapsed (median follow-up of 23 months). CR/CRu was associated with improved survival (p < 0.0001), while a high mantle cell international prognostic index (MIPI) was associated with worse survival (p = 0.05). There was one toxic death (neutropenic pseudomonal sepsis) related to treatment. R-cladribine is an effective therapy for previously untreated MCL, and these results validate the use of R-cladribine for the initial treatment of MCL. C1 [Spurgeon, Stephen E.] Oregon Hlth & Sci Univ, Knight Canc Ctr, Ctr Hematol Malignancies, Knight Canc Inst, Portland, OR 97239 USA. [Pindyck, Talia; Chen, Yiyi; Chen, Zunqiu] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Okada, Craig] Portland VA Med Ctr, Portland, OR USA. [Abbi, Kamal; Epner, Elliot M.] Penn State Hershey Canc Inst, Hershey, PA USA. RP Spurgeon, SE (reprint author), Oregon Hlth & Sci Univ, Knight Canc Ctr, Ctr Hematol Malignancies, Knight Canc Inst, Mailcode UHN 73C,3181 Sam Jackson Pk Rd, Portland, OR 97239 USA. EM spurgeos@ohsu.edu RI abbi, Kamal Kant Singh/M-4189-2014 OI abbi, Kamal Kant Singh/0000-0003-1186-7817 NR 40 TC 17 Z9 19 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD AUG PY 2011 VL 52 IS 8 BP 1488 EP 1494 DI 10.3109/10428194.2011.575489 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 792LU UT WOS:000292747300013 PM 21623691 ER PT J AU Li, YF Wong, ES Sales, AE Sharp, ND Needleman, J Maciejewski, ML Lowy, E Alt-White, AC Liu, CF AF Li, Yu-Fang Wong, Edwin S. Sales, Anne E. Sharp, Nancy D. Needleman, Jack Maciejewski, Matthew L. Lowy, Elliott Alt-White, Anna C. Liu, Chuan-Fen TI Nurse Staffing and Patient Care Costs in Acute Inpatient Nursing Units SO MEDICAL CARE LA English DT Article DE nurse staffing; patient outcomes; mortality; length of stay; health care costs ID VETERANS AFFAIRS HOSPITALS; ADVERSE EVENTS; ADMINISTRATIVE DATA; QUALITY; MORTALITY; OUTCOMES; CLINICS; SAMPLE AB Objective: Studies suggest that a business case for improving nurse staffing can be made to increase registered nurse (RN) skill mix without changing total licensed nursing hours. It is unclear whether a business case for increasing RN skill mix can be justified equally among patients of varying health needs. This study evaluated whether nursing hours per patient day (HPPD) and skill mix are associated with higher inpatient care costs within acute medical/surgical inpatient units using data from the Veterans Health Administration. Methods: Retrospective cross-sectional study, including 139,360 inpatient admissions to 292 acute medical/surgical units at 125 Veterans Health Administration medical centers between February and June 2003, was conducted. Dependent variables were inpatient costs per admission and costs per patient day. Results: The average costs per surgical and medical admission were $18,624 and $6,636, respectively. Costs per admission were positively associated with total nursing HPPD among medical admissions ($164.49 per additional HPPD, P < 0.001), but not among surgical admissions. Total nursing HPPD and RN skill mix were associated with higher costs per hospital day for both medical admissions ($79.02 per additional HPPD and $5.64 per 1% point increase in nursing skill mix, both P < 0.001) and surgical admissions ($112.47 per additional HPPD and $13.31 per 1% point increase in nursing skill mix, both P < 0.001). Patients experiencing complications or transferring to an intensive care unit had higher inpatient costs than other patients. Conclusions: The association of nurse staffing level with costs per admission differed for medical versus surgical admissions. C1 [Li, Yu-Fang; Wong, Edwin S.; Sharp, Nancy D.; Lowy, Elliott; Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA USA. [Li, Yu-Fang] Qual & Safety Analyt Ctr, VA Off, Seattle, WA USA. [Li, Yu-Fang] Univ Washington, Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. [Wong, Edwin S.; Sharp, Nancy D.; Lowy, Elliott; Liu, Chuan-Fen] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Sales, Anne E.] VA Inpatient Evaluat Ctr, Ann Arbor, MI USA. [Needleman, Jack] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Maciejewski, Matthew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27710 USA. [Alt-White, Anna C.] Dept Vet Affairs, Off Nursing Serv, Washington, DC USA. RP Li, YF (reprint author), VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA USA. EM yufang.li@va.gov RI Sales, Anne/D-9678-2012; Needleman, Jack/I-5461-2013 OI Needleman, Jack/0000-0002-2875-0589; Sales, Anne/0000-0001-9360-3334 FU Department of Veterans Affairs, Health Services Research and Development (HSRD) [ECI 04-186]; VA HSRD FX Supported by an Investigator Initiated Research Award (ECI 04-186) from the Department of Veterans Affairs, Health Services Research and Development (HSRD).; Dr Wong is currently supported by the VA HSRD post-doctoral fellowship program. NR 30 TC 5 Z9 5 U1 1 U2 3 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 AUG PY 2011 VL 49 IS 8 BP 708 EP 715 DI 10.1097/MLR.0b013e318223a9f1 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 792PH UT WOS:000292758500005 PM 21758025 ER PT J AU Hawkins, MS Sevick, MA Richardson, CR Fried, LF Arena, VC Kriska, AM AF Hawkins, Marquis S. Sevick, Mary Ann Richardson, Caroline R. Fried, Linda F. Arena, Vincent C. Kriska, Andrea M. TI Association between Physical Activity and Kidney Function: National Health and Nutrition Examination Survey SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE UNITED STATES; GLOMERULAR FILTRATION RATE; ACCELEROMETER; SURVEY ID GLOMERULAR-FILTRATION-RATE; EXAMINATION SURVEY NHANES; CARDIOVASCULAR-DISEASE; RACIAL/ETHNIC GROUPS; METABOLIC SYNDROME; DIABETES-MELLITUS; COMPUTER-SCIENCE; SERUM CREATININE; GLYCEMIC CONTROL; RENAL-FUNCTION AB HAWKINS, M. S., M. A. SEVICK, C. R. RICHARDSON, L. F. FRIED, V. C. ARENA, and A. M. KRISKA. Association between Physical Activity and Kidney Function: National Health and Nutrition Examination Survey. Med. Sci. Sports Exerc., Vol. 43, No. 8, pp. 1457-1464, 2011. Introduction: Chronic kidney disease is a condition characterized by the deterioration of the kidney's ability to remove waste products from the body. Although treatments to slow the progression of the disease are available, chronic kidney disease may eventually lead to a complete loss of kidney function. Previous studies have shown that physical activities of moderate intensity may have renal benefits. Few studies have examined the effects of total movement on kidney function. The purpose of this study was to determine the association between time spent at all levels of physical activity intensity and sedentary behavior and kidney function. Methods: Data were obtained from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Survey, a cross-sectional study of a complex, multistage probability sample of the US population. Physical activity was assessed using an accelerometer and questionnaire. Glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease study formula. To assess linear associations between levels of physical activity and sedentary behavior with log-transformed estimated GFR (eGFR), linear regression was used. Results: In general, physical activity (light and total) was related to log eGFR in females and males. For females, the association between light and total physical activity with log eGFR was consistent regardless of diabetes status. For males, the association between light and total physical activity and log eGFR was only significant in males without diabetes. Conclusions: When examining the association between physical activity, measured objectively with an accelerometer, and kidney function, total and light physical activities were found to be positively associated with kidney function. C1 [Hawkins, Marquis S.; Kriska, Andrea M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Sevick, Mary Ann; Fried, Linda F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Richardson, Caroline R.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Richardson, Caroline R.] Ann Arbor Vet Affairs Med Ctr, HSR&D VA Ctr Clin Management Res, Ann Arbor, MI USA. [Arena, Vincent C.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. RP Hawkins, MS (reprint author), 3512 5th Ave,Room 308, Pittsburgh, PA 15261 USA. EM hawkinsm@edc.pitt.edu OI Arena, Vincent/0000-0002-1634-7207; Kriska, Andrea/0000-0002-3522-0869 NR 38 TC 30 Z9 31 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD AUG PY 2011 VL 43 IS 8 BP 1457 EP 1464 DI 10.1249/MSS.0b013e31820c0130 PG 8 WC Sport Sciences SC Sport Sciences GA 792TM UT WOS:000292773000010 PM 21200336 ER PT J AU Gilden, D Mahalingam, R Nagel, MA Pugazhenthi, S Cohrs, RJ AF Gilden, D. Mahalingam, R. Nagel, M. A. Pugazhenthi, S. Cohrs, R. J. TI Review: The neurobiology of varicella zoster virus infection SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Review DE animal model; apoptosis; latency; neurological disease; VZV ID HUMAN TRIGEMINAL GANGLIA; HERPES-SIMPLEX-VIRUS; AFRICAN-GREEN MONKEYS; POLYMERASE-CHAIN-REACTION; DORSAL-ROOT GANGLIA; BLOOD MONONUCLEAR-CELLS; LATENCY-ASSOCIATED TRANSCRIPT; OUTER RETINAL NECROSIS; HUMAN SENSORY GANGLIA; VZV IGG ANTIBODY AB Varicella zoster virus (VZV) is a neurotropic herpesvirus that infects nearly all humans. Primary infection usually causes chickenpox (varicella), after which virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. Although VZV cannot be isolated from human ganglia, nucleic acid hybridization and, later, polymerase chain reaction proved that VZV is latent in ganglia. Declining VZV-specific host immunity decades after primary infection allows virus to reactivate spontaneously, resulting in shingles (zoster) characterized by pain and rash restricted to one to three dermatomes. Multiple other serious neurological and ocular disorders also result from VZV reactivation. This review summarizes the current state of knowledge of the clinical and pathological complications of neurological and ocular disease produced by VZV reactivation, molecular aspects of VZV latency, VZV virology and VZV-specific immunity, the role of apoptosis in VZV-induced cell death and the development of an animal model provided by simian varicella virus infection of monkeys. C1 [Gilden, D.; Mahalingam, R.; Nagel, M. A.; Cohrs, R. J.] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO 80045 USA. [Gilden, D.] Univ Colorado, Sch Med, Dept Microbiol, Aurora, CO 80045 USA. [Pugazhenthi, S.] Univ Colorado, Sch Med, Dept Med, Aurora, CO 80045 USA. [Pugazhenthi, S.] Denver VA Med Ctr, Denver, CO USA. RP Gilden, D (reprint author), Univ Colorado, Sch Med, Dept Neurol, 12700 E 19th Ave,Box B182, Aurora, CO 80045 USA. EM don.gilden@ucdenver.edu FU NIH [AG006127, AG032958, NS067070]; Veterans Administration [NEUD-004-07F] FX The authors' studies cited in this Review were funded by NIH grants AG006127 to DG, AG032958 to DG, SP, RJC and NS067070 to MAN; and Merit Review grant NEUD-004-07F from the Veterans Administration to SP. NR 202 TC 57 Z9 58 U1 3 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD AUG PY 2011 VL 37 IS 5 BP 441 EP 463 DI 10.1111/j.1365-2990.2011.01167.x PG 23 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 791VF UT WOS:000292694300001 PM 21342215 ER PT J AU Brady, KT Gray, KM Tolliver, BK AF Brady, Kathleen T. Gray, Kevin M. Tolliver, Bryan K. TI Cognitive enhancers in the treatment of substance use disorders: Clinical evidence SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Review DE Cognition; Addiction; Pharmacotherapy; Medications; Substance use disorders; Learning and memory ID PLACEBO-CONTROLLED TRIAL; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; COCAINE-DEPENDENT INDIVIDUALS; TOBACCO WITHDRAWAL SYNDROME; DRUG-SEEKING BEHAVIOR; DOUBLE-BLIND; D-CYCLOSERINE; METHAMPHETAMINE DEPENDENCE; PREFRONTAL CORTEX AB Attenuation of drug reward has been the major focus of medication development in the addiction area to date. With the growth of research in the area of cognitive neuroscience, the importance of executive function and inhibitory cognitive control in addictive disorders is becoming increasingly apparent. An emerging strategy in the pharmacotherapy of addictions and other psychiatric disorders involves the use of medications that improve cognitive function. In particular, agents that facilitate inhibitory and attentional control, improve abstraction, planning and mental flexibility could be beneficial in the treatment of substance use disorders. Because there are multiple neurotransmitter systems involved in the regulation of cognitive function, agents from a number of drug classes have been tested. In particular, agents acting through the cholinergic, adrenergic and glutamatergic systems have shown potential for improving cognitive function in a number of psychiatric and neurologic disorders, but most of these agents have not been tested in the treatment of individuals with substance use disorders. This manuscript provides a review of clinical data supporting the use of the major classes of cognitive enhancing agents in substance use disorders. Agents that have shown promise in cognitive enhancement in other disorders, and have a theoretical or mechanistic rationale for application to substance use disorders are also highlighted. (C) 2011 Elsevier Inc. All rights reserved. C1 [Brady, Kathleen T.; Gray, Kevin M.; Tolliver, Bryan K.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Brady, Kathleen T.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Brady, KT (reprint author), Med Univ S Carolina, Dept Psychiat, 67 President St, Charleston, SC 29425 USA. EM bradyk@musc.edu; graykm@musc.edu; tollive@musc.edu FU NIDA NIH HHS [R01 DA023188-03, R01 DA023188-04, R01 DA026777, R21 DA026085, R21 DA026085-02, R25 DA020537, R01 DA023188] NR 140 TC 37 Z9 39 U1 7 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD AUG PY 2011 VL 99 IS 2 SI SI BP 285 EP 294 DI 10.1016/j.pbb.2011.04.017 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 791OA UT WOS:000292673300015 PM 21557964 ER PT J AU Kearney, DJ McDermott, K Martinez, M Simpson, TL AF Kearney, D. J. McDermott, K. Martinez, M. Simpson, T. L. TI Association of participation in a mindfulness programme with bowel symptoms, gastrointestinal symptom-specific anxiety and quality of life SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID VISCERAL SENSITIVITY INDEX; PTSD CHECKLIST; HEALTH-STATUS; PSYCHOMETRIC PROPERTIES; PSYCHOLOGICAL TREATMENT; ALTERNATIVE MEDICINE; BEHAVIORAL TREATMENT; COGNITIVE THERAPY; CONTROLLED TRIAL; UNITED-STATES AB Background Stress perception and GI-specific anxiety play key roles in irritable bowel syndrome (IBS). Mindfulness-based stress reduction (MBSR) is a widely available stress reduction course, which has not been evaluated for IBS. Aim To determine whether participation in MBSR is associated with improvement in bowel symptoms, GI-specific anxiety, and IBS-Quality of Life. Methods This is a prospective study of 93 participants in MBSR. We applied measures of Rome III IBS status, bowel symptoms (IBS-Severity Scoring System, IBS-SSS), IBS-Quality of Life (IBS-QOL), GI-specific anxiety (Visceral Sensitivity Index, VSI), mindfulness (Five Facet Mindfulness Questionnaire-FFMQ), and functional status (SF-8) at baseline and 2 and 6 months after enrolment. Results At 2 months, participation in MBSR was associated with small nonsignificant changes in IBS-SSS, IBS-QOL and VSI: d = -0.25, d = 0.08, d = -0.16, respectively. At 6 months, there was no significant change in IBS-SSS (d = -0.36); whereas for IBS-QOL and VSI there were significant improvements (IBS-QOL: d = 0.33, P = 0.044; VSI: d = -0.40, P = 0.014). For patients meeting Rome III IBS criteria (n = 43), changes in IBS-SSS, IBS-QOL and VSI were not statistically significant, but there was a significant correlation between the change in VSI and the change in FFMQ across the three time periods (r = 0.33). Conclusions Participation in MBSR is associated with improvement IBS-related quality of life and GI-specific anxiety. Randomised controlled trials are warranted to further assess the role of MBSR for IBS symptomatology. C1 [Kearney, D. J.] Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. [McDermott, K.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Simpson, T. L.] VA Puget Sound Hlth Care Syst, CESATE, Seattle, WA USA. [Simpson, T. L.] VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA USA. [Simpson, T. L.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Kearney, DJ (reprint author), Seattle VAMC 111GI,1660 S Columbian Way, Seattle, WA 98108 USA. EM David.kearney@va.gov FU VA Puget Sound Health Care System FX Declaration of personal interests: This work was supported by resources from VA Puget Sound Health Care System. We wish to thank Kurt Hoelting, M. Div., who taught some of the MBSR courses for this study. We also wish to thank the Veterans who participated in this research. Declaration of funding interests: None. NR 64 TC 20 Z9 20 U1 2 U2 23 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD AUG PY 2011 VL 34 IS 3 BP 363 EP 373 DI 10.1111/j.1365-2036.2011.04731.x PG 11 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 787RQ UT WOS:000292394800011 PM 21651595 ER PT J AU Walker, RH AF Walker, Ruth H. TI Differential Diagnosis of Chorea SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Chorea; Huntington's disease; Basal ganglia; Neuroacanthocytosis; Huntington disease-like ID DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY; CALCIFICATION FAHR-DISEASE; CREUTZFELDT-JAKOB-DISEASE; BENIGN HEREDITARY CHOREA; DEEP BRAIN-STIMULATION; ADULT-ONSET CHOREA; TERM-FOLLOW-UP; HUNTINGTONS-DISEASE; BASAL GANGLIA; MOVEMENT-DISORDERS AB Chorea is a common movement disorder that can be caused by a large variety of structural, neurochemical (including pharmacologic), or metabolic disturbances to basal ganglia function, indicating the vulnerability of this brain region. The diagnosis is rarely indicated by the simple phenotypic appearance of chorea, and can be challenging, with many patients remaining undiagnosed. Clues to diagnosis may be found in the patient's family or medical history, on neurologic examination, or upon laboratory testing and neuroimaging. Increasingly, advances in genetic medicine are identifying new disorders and expanding the phenotype of recognized conditions. Although most therapies at present are supportive, correct diagnosis is essential for appropriate genetic counseling, and ultimately, for future molecular therapies. C1 [Walker, Ruth H.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY 10468 USA. [Walker, Ruth H.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. RP Walker, RH (reprint author), James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY 10468 USA. EM ruth.walker@mssm.edu NR 103 TC 6 Z9 6 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD AUG PY 2011 VL 11 IS 4 BP 385 EP 395 DI 10.1007/s11910-011-0202-2 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 788RU UT WOS:000292462900005 PM 21465146 ER PT J AU Lin, JC Guerrieri, JG Moore, AA AF Lin, James C. Guerrieri, Joy Gioia Moore, Alison A. TI Drinking Patterns and the Development of Functional Limitations in Older Adults: Longitudinal Analyses of the Health and Retirement Survey SO JOURNAL OF AGING AND HEALTH LA English DT Article DE alcohol; drinking patterns; functional limitations ID MODERATE ALCOHOL-CONSUMPTION; CORONARY-HEART-DISEASE; ISCHEMIC-STROKE; UNITED-STATES; US ADULTS; AGE 50; MORTALITY; RISK; MEN; PEOPLE AB Objective: To examine whether consistent low-risk drinking is associated with lower risk of developing functional limitations among older adults. Method: Data were obtained from five waves of the Health and Retirement Study. Function was assessed by questions measuring four physical abilities and five instrumental activities of daily living. Five different drinking patterns were determined using data over two consecutive survey periods. Results: Over the follow-up periods, 38.6% of older adults developed functional limitations. Consistent low-risk drinkers had lower odds of developing functional limitations compared with consistent abstainers, and the effect of consistent low-risk drinking was greater among those aged 50 to 64 years compared with those aged >= 65 years. Other drinking patterns were not associated with lower odds of incident functional limitation. Discussion: Consistent low-risk drinking was associated with lower odds of developing functional limitations, and this association was greater among older middle-aged adults aged 50 to 64 years. C1 [Lin, James C.] Cheng Ching Hosp, Dept Med, Taichung 40764, Taiwan. [Lin, James C.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Guerrieri, Joy Gioia] Mayo Clin, Rochester, MN USA. [Moore, Alison A.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Lin, JC (reprint author), Cheng Ching Hosp, Dept Med, 118 Sec 3,Chun Kang Rd, Taichung 40764, Taiwan. EM jlin1207@ucla.edu FU NIA NIH HHS [P30 AG021684, P30 AG021684-07, P30AG021684, T35 AG026736, T35 AG026736-06]; NIAAA NIH HHS [R01 AA013937, K24 AA015957, K24 AA015957-04, K24 AA15957] NR 37 TC 13 Z9 13 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD AUG PY 2011 VL 23 IS 5 BP 806 EP 821 DI 10.1177/0898264310397541 PG 16 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 788NE UT WOS:000292450900003 PM 21311049 ER PT J AU Banaszak-Holl, J Liang, J Quinones, A Cigolle, C Lee, IC Verbrugge, LM AF Banaszak-Holl, Jane Liang, Jersey Quinones, Ana Cigolle, Christine Lee, I-Cha Verbrugge, Lois M. TI Trajectories of Functional Change Among Long Stayers in Nursing Homes: Does Baseline Impairment Matter? SO JOURNAL OF AGING AND HEALTH LA English DT Article DE health services; nursing homes; physical function ID MINIMUM DATA SET; RESIDENT ASSESSMENT INSTRUMENT; SELF-RATED HEALTH; DISABLEMENT PROCESS; OLDER PERSONS; TERM-CARE; RELIABILITY; FRAILTY; MDS; DISABILITY AB Objectives: This study reports findings on functional change trajectories for long-stay residents by examining the effects of baseline medical conditions and functional status on changes in physical impairment across residents' length of stay (LOS). Method: A 5% sample of nursing home residents from Michigan from 1999 through 2003 was used to create longitudinal episodes of care including Minimum Data Set (MDS) assessments. Data were analyzed using hierarchical linear models. Results: On average, physical impairment increases throughout a resident's stay and is more rapid later in the stay. Greater physical and cognitive impairment at baseline leads to increasing impairment for residents whereas presence of baseline medical conditions, including heart disease and hip fracture, leads to slower rates of impairment. Discussion: Baseline functional status is critical to predicting changes in impairment while the impact of medical diagnoses is significant but weaker than the effect of baseline impairment. C1 [Banaszak-Holl, Jane] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Quinones, Ana] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Quinones, Ana] Portland VA Med Ctr, Portland, OR USA. [Cigolle, Christine] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Lee, I-Cha] Univ Calif Irvine, Irvine, CA USA. RP Banaszak-Holl, J (reprint author), Univ Michigan, Sch Publ Hlth, 1415 Washington Hts, Ann Arbor, MI 48109 USA. EM janebh@umich.edu FU NIA NIH HHS [K08 AG031837] NR 42 TC 3 Z9 3 U1 2 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD AUG PY 2011 VL 23 IS 5 BP 862 EP 882 DI 10.1177/0898264311399759 PG 21 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 788NE UT WOS:000292450900006 PM 21436394 ER PT J AU Blum, JL Kinsey, GR Monian, P Sun, B Cummings, BS McHowat, J Schnellmann, RG AF Blum, Jason L. Kinsey, Gilbert R. Monian, Prashant Sun, Bin Cummings, Brian S. McHowat, Jane Schnellmann, Rick G. TI Profiling of fatty acids released during calcium-induced mitochondrial permeability transition in isolated rabbit kidney cortex mitochondria SO TOXICOLOGY IN VITRO LA English DT Article DE Fatty acid profiling; Kidney; Calcium-independent phospholipase A(2) gamma; Mitochondrial swelling ID CA2+-INDEPENDENT PHOSPHOLIPASE A(2); CELL-DEATH; LIVER-MITOCHONDRIA; OXIDATIVE STRESS; INNER MEMBRANE; APOPTOSIS; METABOLISM; CA2+; IDENTIFICATION; ACCUMULATION AB Increases in intracellular Ca(2+) during cellular stress often lead to the mitochondrial permeability transition (MPT). We examined changes in fatty acids (FAs) released from isolated renal cortical mitochondria subjected to Ca(2+)-induced MPT. Exposing mitochondria to Ca(2+) stimulated mitochondrial swelling and release of FAs such as arachidonic (20:4) and docosahexenoic acids which increased 71% and 32%, respectively, and linoleic (18:2) which decreased 23% compared to controls. Stearic (18:0), oleic (18:1), and linoleic (18:3) acids were unchanged. To elucidate a mechanism for FA release, mitochondria were pre-treated with bromoenolactone (BEL) to inhibit Ca(2+)-independent phospholipase A(2) gamma activity (iPLA(2)gamma). BEL blocked Ca(2+)-induced release of arachidonic and behenic (22:0) acids. Finally, four FAs were released in the absence of Ca(2+) in a BEL-sensitive manner, including arachidonic and docosatrienoic acids. Thus, extensive FA release occurs during Ca(2+)-induced MPT, and that mitochondrial iPLA(2)gamma maintains mitochondrial arachidonic acid homeostasis under both basal and Ca(2+)-induced stress conditions. Published by Elsevier Ltd. C1 [Blum, Jason L.; Kinsey, Gilbert R.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Coll Pharm, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson VA Med Ctr Charleston, Charleston, SC 29401 USA. [Monian, Prashant; Sun, Bin; Cummings, Brian S.] Univ Georgia, Coll Pharm, Dept Pharmaceut & Biomed Sci, Athens, GA 30602 USA. [McHowat, Jane] St Louis Univ, Sch Med, Dept Pathol, St Louis, MO 63104 USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Coll Pharm, Ctr Cell Death Injury & Regenerat, POB 250140, Charleston, SC 29425 USA. EM schnell@musc.edu RI Kinsey, Gilbert/J-8322-2012 OI Blum, Jason/0000-0003-1381-6802 FU National Institutes of Health [DK-62028, C06 RR-015455, P20 RR-016461]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs; National Institutes of Health National Research Service [F32 DK-081267] FX This work was supported by a National Institutes of Health Grant No. DK-62028 and by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. to RGS. J.L.B. was supported by an individual National Institutes of Health National Research Service Award training fellowship (F32 DK-081267). The Medical University of South Carolina animal facilities were funded by National Institutes of Health Grant No. C06 RR-015455. The South Carolina INBRE was funded by National Institutes of Health Grant No. P20 RR-016461. The authors also thank Dr. Yefim Manevich (Medical University of South Carolina) for his advice and constructive discussions during the execution of these experiments and Dr. Jennifer Schnellmann for her assistance in preparing this manuscript. NR 36 TC 7 Z9 7 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD AUG PY 2011 VL 25 IS 5 BP 1001 EP 1006 DI 10.1016/j.tiv.2011.03.014 PG 6 WC Toxicology SC Toxicology GA 787HH UT WOS:000292366700001 PM 21443943 ER PT J AU De Costa, AM Young, MRI AF De Costa, Anna-Maria Young, M. Rita I. TI Immunotherapy for head and neck cancer: advances and deficiencies SO ANTI-CANCER DRUGS LA English DT Review DE head and neck cancer; head and neck squamous cell carcinomas; immunosuppression; immunotherapy; suppressor cells; tumor antigens ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; CD34(+) PROGENITOR CELLS; REGULATORY T-CELLS; PHASE-II TRIAL; REFRACTORY COLORECTAL-CANCER; PERIPHERAL-BLOOD; INTERFERON-ALPHA; CLINICAL-TRIAL; DENDRITIC CELLS AB The concept of immunotherapy as a treatment for cancer patients has been in existence for decades. However, more recent immune therapeutic approaches have involved targeting of tumor-specific antigens. Although improvements have been made in using such immune stimulatory treatment strategies for a variety of solid cancers, the use of these strategies for patients with head and neck squamous cell carcinoma (HNSCC) is lagging behind. Immunotherapeutic approaches for HNSCC are particularly complicated by the profound immune suppression that is induced by HNSCC, which potentially decreases the effectiveness of immune stimulatory efforts. Trials involving patients with various solid cancers have shown the enhanced effectiveness of combining various immunotherapeutic approaches or combining immunotherapy with chemotherapy or radiation therapy. Treatment of HNSCC with such combination approaches has not been extensively investigated and has the added challenge of the need to overcome the HNSCC-induced immune suppression. This study focuses on clinical trials that have tested immunotherapeutic approaches for HNSCC patients and the challenges associated with such approaches. In addition, it will call attention to immunotherapeutic strategies that have been shown to be successful in the treatment of other solid cancers to identify potential strategies that may apply to the treatment of HNSCC. Anti-Cancer Drugs 22: 674-681 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [De Costa, Anna-Maria; Young, M. Rita I.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. [De Costa, Anna-Maria] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Young, MRI (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Res Serv 151, Charleston, SC 29401 USA. EM rita.young@va.gov FU Clinical Science and Biomedical Laboratory Research and Development Services of the Department of Veterans Affairs; National Institutes of Health [R01 DE018168, R01CA128837] FX This study was supported by the Clinical Science and Biomedical Laboratory Research and Development Services of the Department of Veterans Affairs, and by Grants R01 DE018168 and R01CA128837 from the National Institutes of Health to MRIY. NR 85 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD AUG PY 2011 VL 22 IS 7 BP 674 EP 681 DI 10.1097/CAD.0b013e328340fd18 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 782SS UT WOS:000292032200014 PM 21037467 ER PT J AU Stein, DJ Craske, MG Friedman, MJ Phillips, KA AF Stein, Dan J. Craske, Michelle G. Friedman, Matthew J. Phillips, Katharine A. TI Meta-structure Issues for the DSM-5: How Do Anxiety Disorders, Obsessive-Compulsive and Related Disorders, Post-Traumatic Disorders, and Dissociative Disorders Fit Together? SO CURRENT PSYCHIATRY REPORTS LA English DT Editorial Material DE DSM-5; ICD-11; Anxiety disorders; Obsessive-compulsive disorder; Post-traumatic disorders; Dissociative disorders; Classification; Stereotypic disorders; Pathophysiology; Etiology; Category; Nosology AB The question of how to optimally organize into chapters and label the different categories of mental disorders is an important one for DSM-5 and ICD-11. The grouping of mental disorders, or meta-structure, should arguably reflect knowledge on the validity of different conditions and their relationships, and should ideally contribute to improving the clinical utility of the nosology by guiding clinical assessment and management. The DSM-5 Anxiety, Obsessive-Compulsive Spectrum, Posttraumatic, and Dissociative Disorders Workgroup has reviewed the nature of anxiety disorders, the possibility of including a new category of obsessive-compulsive spectrum disorders in the DSM-5, and the concept of traumatic stress disorders. It is difficult to devise a perfect nosology that dissects nature at her joints; instead, any particular approach to the meta-structure would seem to have pros and cons that must be carefully weighed. Despite the imperfections of any meta-structure, we are hopeful that each revision of the nosology will bring with it greater diagnostic validity and clinical utility. C1 [Stein, Dan J.] Univ Cape Town, Dept Psychiat, Groote Schuur Hosp J2, ZA-7925 Cape Town, South Africa. [Craske, Michelle G.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Craske, Michelle G.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Friedman, Matthew J.] US Dept Vet Affairs, Natl Ctr PTSD, Hanover, NH USA. [Friedman, Matthew J.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Psychiat, Hanover, NH 03756 USA. [Friedman, Matthew J.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03756 USA. [Phillips, Katharine A.] Brown Univ, Alpert Med Sch, Rhode Isl Hosp, Providence, RI 02912 USA. [Phillips, Katharine A.] Brown Univ, Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. RP Stein, DJ (reprint author), Univ Cape Town, Dept Psychiat, Groote Schuur Hosp J2, Anzio Rd, ZA-7925 Cape Town, South Africa. EM dan.stein@uct.ac.za RI Stein, Dan/A-1752-2008 OI Stein, Dan/0000-0001-7218-7810 NR 8 TC 24 Z9 25 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD AUG PY 2011 VL 13 IS 4 BP 248 EP 250 DI 10.1007/s11920-011-0207-1 PG 3 WC Psychiatry SC Psychiatry GA 786KY UT WOS:000292308400003 PM 21603904 ER PT J AU Das, F Dey, N Venkatesan, B Kasinath, BS Ghosh-Choudhury, N Choudhury, GG AF Das, Falguni Dey, Nirmalya Venkatesan, Balachandar Kasinath, Balakuntalam S. Ghosh-Choudhury, Nandini Choudhury, Goutam Ghosh TI High glucose upregulation of early-onset Parkinson's disease protein DJ-1 integrates the PRAS40/TORC1 axis to mesangial cell hypertrophy SO CELLULAR SIGNALLING LA English DT Article DE Akt kinase; Kidney; Diabetes; mTOR ID TUMOR-SUPPRESSOR PTEN; MESSENGER-RNA TRANSLATION; DIABETIC-NEPHROPATHY; OXIDATIVE STRESS; RENAL HYPERTROPHY; PI3K PATHWAY; AKT KINASE; GENE DJ-1; BINDING; RAPAMYCIN AB The Akt kinase signaling pathway is frequently deregulated in many human diseases including cancer, autoimmune disease and diabetes. In nephropathy, associated with diabetes, increased Akt signal transduction results in glomerular especially mesangial cell hypertrophy. The mechanism of Akt activation by elevated glucose is poorly understood. The oncogene DJ-1 prevents oxidative damage and apoptosis of dopaminergic neurons in animal models of Parkinson's disease and in culture. We identified DJ-1 to increase in response to high glucose in renal glomerular mesangial cells concomitant with an increase in phosphorylation of Akt in a time-dependent manner. Plasmid-derived overexpression as well as down-regulation of DJ-1 by siRNA showed the requirement of this protein in high glucose-stimulated Akt phosphorylation. The tumor suppressor protein PTEN acts as a negative regulator of Akt activation. Interestingly, DJ-1 was associated with PTEN and this interaction was significantly increased in response to high glucose. High glucose-induced increase in DJ-1 promoted phosphorylation of the PRAS40, a negative regulator of TORC1 kinase activity, resulting in activating and inactivating phosphorylation of S6 kinase and 4EBP-1, respectively. Furthermore, DJ-1 increased protein synthesis and hypertrophy of mesangial cells. Our results provide evidence for a unique mechanism whereby DJ-1 induces Akt/PRAS40/TORC1-mediated hypertrophy in response to high glucose. (C) 2011 Elsevier Inc. All rights reserved. C1 [Das, Falguni; Dey, Nirmalya; Venkatesan, Balachandar; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Kasinath, Balakuntalam S.; Ghosh-Choudhury, Nandini; Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, VA Res, San Antonio, TX USA. [Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Res, San Antonio, TX USA. [Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. RP Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu FU Juvenile Diabetes Research Foundation [1-2008-185]; NIH [RO1 DK50190, RO1 AR52425, DK 077295, RC2A 036613]; VA Research Service; Cancer Therapy and Research Center, San Antonio FX The authors thank Drs. Brent Wagner and Anthony J. Valente, Department of Medicine, University of Texas Health Science Center at San Antonio for critically reading the manuscript. This work was supported by The Juvenile Diabetes Research Foundation 1-2008-185 and NIH RO1 DK50190 grants to GGC. GGC is a recipient of VA Senior Research Career Scientist Award and is supported by VA Research Service Merit Review grant. NGC is supported by VA Merit Review, Ronald P Williams Orthopedic Oncology Developmental Research Award from Cancer Therapy and Research Center, San Antonio and NIH RO1 AR52425 grants. BSK is supported by grants from NIH (DK 077295 and RC2A 036613) and VA Research Service. NR 49 TC 24 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD AUG PY 2011 VL 23 IS 8 BP 1311 EP 1319 DI 10.1016/j.cellsig.2011.03.012 PG 9 WC Cell Biology SC Cell Biology GA 776BO UT WOS:000291509700010 PM 21426932 ER PT J AU Egan, GJ Hasenkamp, W Wilcox, L Green, A Hsu, N Boshoven, W Lewison, B Keyes, MD Duncan, E AF Egan, Glenn J. Hasenkamp, Wendy Wilcox, Lisette Green, Amanda Hsu, Nancy Boshoven, William Lewison, Barbara Keyes, Megan D. Duncan, Erica TI Declarative memory and WCST-64 performance in subjects with schizophrenia and healthy controls SO PSYCHIATRY RESEARCH LA English DT Article DE Wisconsin Card Sorting Test; Benton Visual Retention Test; California Verbal Learning Test; Executive functioning ID CARD-SORTING TEST; ASSOCIATE RECOGNITION TEST; NEUROCOGNITIVE DEFICITS; NEUROPSYCHOLOGICAL DEFICITS; DYSFUNCTION; RELIABILITY; VALIDITY; STIMULI; SCALE AB The Wisconsin Card Sorting Test (WCST) is a set-switching task used extensively to study impaired executive functioning in schizophrenia. Declarative memory deficits have also been associated with schizophrenia and may affect WCST performance because continued correct responding depends on remembering the outcome of previous responses. This study examined whether performance in visual and verbal declarative memory tasks were associated with WCST performance. Subjects comprised 30 patients with schizophrenia or schizoaffective disorder (SCZ) and 30 demographically matched healthy controls (CON) who were tested on the WCST, the Benton Visual Retention Test (BVRT), the California Verbal Learning Test (CVLT), and the Continuous Performance Test (CPT). SCZ subjects showed significant correlations between visual and verbal declarative memory and performance on the WCST-64 that were in the hypothesized direction such that worse memory performance was associated with worse performance on the WCST. CON subjects did not show a significant relationship between visual or verbal memory and WCST-64 performance. Fisher's r to z transformations indicated that the associations between declarative memory and WCST-64 performance in the SCZ subjects differed significantly from those of CON subjects. The findings suggest that interpretations of WCST-64 scores for subjects with schizophrenia should be considered in light of their declarative memory functioning. (C) 2011 Published by Elsevier Ireland Ltd. C1 [Egan, Glenn J.; Boshoven, William; Lewison, Barbara; Duncan, Erica] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30303 USA. [Egan, Glenn J.; Hasenkamp, Wendy; Wilcox, Lisette; Lewison, Barbara; Duncan, Erica] Atlanta VA Med Ctr, Decatur, GA USA. [Green, Amanda] Grady Mem Hosp, Atlanta, GA USA. [Hsu, Nancy] Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA. [Keyes, Megan D.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Egan, GJ (reprint author), Emory Univ, Sch Med, Dept Psychiat, 49 Jesse Hill Jr Dr SE, Atlanta, GA 30303 USA. EM glenn.egan@emory.edu RI Duncan, Erica/B-1671-2016 FU Veterans Affairs Merit Review Grant Program; National Institute on Drug Addiction [MH1R01DA018294-01A2]; Mental Health Service and Research and Development Service at the Atlanta Veterans Affairs Medical Center; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine FX This study was primarily supported by the Veterans Affairs Merit Review Grant Program (E. Duncan). Additional support was received from the National Institute on Drug Addiction (MH1R01DA018294-01A2, E. Duncan), the Mental Health Service and Research and Development Service at the Atlanta Veterans Affairs Medical Center, and the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine. The authors are grateful for the editorial assistance of Griffin Fry. NR 44 TC 5 Z9 5 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUL 30 PY 2011 VL 188 IS 2 BP 191 EP 196 DI 10.1016/j.psychres.2011.02.026 PG 6 WC Psychiatry SC Psychiatry GA 791OM UT WOS:000292674500003 PM 21481945 ER PT J AU Korb, MA Thakkar, U AF Korb, Michele A. Thakkar, Umesh TI Facilitating Scientific Investigations and Training Data Scientists SO SCIENCE LA English DT Editorial Material C1 [Korb, Michele A.] Calif State Univ Hayward, Dept Teacher Educ, Coll Educ & Allied Studies, Hayward, CA 94542 USA. [Thakkar, Umesh] Univ Illinois, Coordinated Sci Lab, Urbana, IL 61801 USA. [Thakkar, Umesh] Vet Hlth Adm, Off Publ Hlth, US Dept Vet Affairs, Washington, DC 20420 USA. RP Korb, MA (reprint author), Calif State Univ Hayward, Dept Teacher Educ, Coll Educ & Allied Studies, Hayward, CA 94542 USA. EM michele.korb@csueastbay.edu; uthakkar@illinois.edu NR 8 TC 0 Z9 0 U1 0 U2 2 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 JUL 29 PY 2011 VL 333 IS 6042 BP 534 EP 535 DI 10.1126/science.1196981 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 798PI UT WOS:000293222400032 PM 21798922 ER PT J AU Tugwell, P Singh, JA Wells, GA AF Tugwell, Peter Singh, Jasvinder A. Wells, George A. TI THERAPEUTICS Biologicals for rheumatoid arthritis SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID MODIFYING ANTIRHEUMATIC DRUGS; EULAR RECOMMENDATIONS; DISEASE; SAFETY; MANAGEMENT; INFLIXIMAB; AGENTS AB This is one of a series of occasional articles on therapeutics for common or serious conditions, covering new drugs and old drugs with important new indications or concerns. The series advisers are Robin Ferner, honorary professor of clinical pharmacology, University of Birmingham and Birmingham City Hospital, and Philip Routledge, professor of clinical pharmacology, Cardiff University. To suggest a topic for this series, please email us at practice@bmj.com. C1 [Tugwell, Peter] Univ Ottawa, Dept Med, Inst Populat Hlth, Ottawa, ON K1N 6N5, Canada. [Tugwell, Peter] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON K1N 6N5, Canada. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama, Birmingham, AL 35294 USA. [Wells, George A.] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. [Wells, George A.] Univ Ottawa, Inst Heart, Ottawa, ON, Canada. RP Tugwell, P (reprint author), Univ Ottawa, Dept Med, Inst Populat Hlth, Ottawa, ON K1N 6N5, Canada. EM tugwell.bb@uottawa.ca OI singh, jasvinder/0000-0003-3485-0006; Tugwell, Peter/0000-0001-5062-0556 FU Canadian Institutes of Health Research (CIHR); Takeda; Savient; Wyeth; Amgen; URL Pharma; Novartis; Bristol-Myers Squibb FX All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work. PT received honorariums for quality of life consultancy with Bristol-Myers Squibb; chairs data safety monitoring boards for Chelsea Therapeutics and UCB, mandated for the Food and Drug Administration; is a member of the executive of OMERACT, an organisation that develops outcome measures in rheumatology and receives "arms length" funding from 36 companies; co-chaired an industry board of six companies (Abbott, Bristol-Myers Squibb, Merck, Roche, Schering Plough, UCB) for a biologicals registry of the Ontario Rheumatology Association, the Ontario Biologics Research Initiative (an arms-length registry that independently collects information, supported by a grant from the Canadian Institutes of Health Research (CIHR) matched by funding from these drug companies); and receives an honorarium from the CIHR grant. JAS has received speaker honorariums from Abbott, research and travel grants from Takeda, Savient, Wyeth, and Amgen, and consultant fees from URL Pharma, Takeda, Savient, and Novartis; he is a member of the executive of OMERACT. GAW received honorariums for consultancy with Novartis, Bristol-Myers Squibb, and Abbott; a grant from Bristol-Myers Squibb; and speaker honorariums from Abbott; he is a member of the executive of OMERACT and of the Scientific Committee for the Ontario Biologics Research Initiative. NR 23 TC 7 Z9 7 U1 0 U2 4 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 JUL 28 PY 2011 VL 343 AR d4027 DI 10.1136/bmj.d4027 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 801LT UT WOS:000293441100001 PM 21798970 ER PT J AU Vaid, M Prasad, R Sun, Q Katiyar, SK AF Vaid, Mudit Prasad, Ram Sun, Qian Katiyar, Santosh K. TI Silymarin Targets beta-Catenin Signaling in Blocking Migration/Invasion of Human Melanoma Cells SO PLOS ONE LA English DT Article ID CUTANEOUS MELANOMA; COLORECTAL-CANCER; PATHWAY; EXPRESSION; CYCLOOXYGENASE-2; LOCALIZATION; INHIBITION; ACTIVATION; MUTATIONS; GROWTH AB Metastatic melanoma is a leading cause of death from skin diseases, and is often associated with activation of Wnt/beta-catenin signaling pathway. We have examined the inhibitory effect of silymarin, a plant flavanoid from Silybum marianum, on cell migration of metastasis-specific human melanoma cell lines (A375 and Hs294t) and assessed whether Wnt/beta-catenin signaling is the target of silymarin. Using an in vitro invasion assay, we found that treatment of human melanoma cell lines with silymarin resulted in concentration-dependent inhibition of cell migration, which was associated with accumulation of cytosolic beta-catenin, while reducing the nuclear accumulation of beta-catenin (i.e., b-catenin inactivation) and reducing the levels of matrix metalloproteinase (MMP)-2 and MMP-9 which are the down-stream targets of beta-catenin. Silymarin enhanced: (i) the levels of casein kinase 1 alpha, glycogen synthase kinase-3 beta and phosphorylated-beta-catenin on critical residues Ser(45), Ser(33/37) and Thr(41), and (ii) the binding of beta-transducin repeat-containing proteins (beta-TrCP) with phospho forms of beta-catenin in melanoma cells. These events play important roles in degradation or inactivation of beta-catenin. To verify whether beta-catenin is a potent molecular target of silymarin, the effect of silymarin was determined on beta-catenin-activated (Mel 1241) and beta-catenin-inactivated (Mel 1011) melanoma cells. Treatment of Mel 1241 cells with silymarin or FH535, an inhibitor of Wnt/beta-catenin pathway, significantly inhibited cell migration of Mel 1241 cells, which was associated with the elevated levels of casein kinase 1 alpha and glycogen synthase kinase-3 beta, and decreased accumulation of nuclear beta-catenin and inhibition of MMP-2 and MMP-9 levels. However, this effect of silymarin and FH535 was not found in Mel 1011 melanoma cells. These results indicate for the first time that silymarin inhibits melanoma cell migration by targeting beta-catenin signaling pathway. C1 [Vaid, Mudit; Prasad, Ram; Sun, Qian; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Vaid, M (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 31 TC 54 Z9 56 U1 0 U2 8 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 JUL 28 PY 2011 VL 6 IS 7 AR e23000 DI 10.1371/journal.pone.0023000 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 799KC UT WOS:000293284600070 PM 21829575 ER PT J AU Merkow, RP Ko, CY AF Merkow, Ryan P. Ko, Clifford Y. TI Evidence-Based Medicine in Surgery The Importance of Both Experimental and Observational Study Designs SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID RANDOMIZED CLINICAL-TRIAL; INVASIVE BREAST-CANCER; ANTIREFLUX SURGERY; FOLLOW-UP; TOTAL MASTECTOMY; IRRADIATION C1 [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Merkow, Ryan P.] Univ Colorado, Sch Med, Dept Surg, Aurora, CO USA. [Merkow, Ryan P.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Merkow, Ryan P.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. RP Ko, CY (reprint author), Univ Calif Los Angeles, Dept Surg, 10833 LeConte Ave 72-215 CHS, Los Angeles, CA 90095 USA. EM cko@mednet.ucla.edu NR 12 TC 23 Z9 23 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 JUL 27 PY 2011 VL 306 IS 4 BP 436 EP 437 DI 10.1001/jama.2011.1059 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 797KL UT WOS:000293125800033 PM 21791695 ER PT J AU Middleton, LE Manini, TM Simonsick, EM Harris, TB Barnes, DE Tylavsky, F Brach, JS Everhart, JE Yaffe, K AF Middleton, Laura E. Manini, Todd M. Simonsick, Eleanor M. Harris, Tamara B. Barnes, Deborah E. Tylavsky, Frances Brach, Jennifer S. Everhart, James E. Yaffe, Kristine TI Activity Energy Expenditure and Incident Cognitive Impairment in Older Adults SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PHYSICAL-ACTIVITY QUESTIONNAIRES; ALZHEIMERS-DISEASE; EXERCISE; DEMENTIA; DECLINE; HEALTH; RISK; WOMEN; VARIABILITY; POPULATION AB Background: Studies suggest that physically active people have reduced risk of incident cognitive impairment in late life. However, these studies are limited by reliance on self-reports of physical activity, which only moderately correlate with objective measures and often exclude activity not readily quantifiable by frequency and duration. The objective of this study was to investigate the relationship between activity energy expenditure (AEE), an objective measure of total activity, and incidence of cognitive impairment. Methods: We calculated AEE as 90% of total energy expenditure (assessed during 2 weeks using doubly labeled water) minus resting metabolic rate (measured using indirect calorimetry) in 197 men and women (mean age, 74.8 years) who were free of mobility and cognitive impairments at study baseline (1998-1999). Cognitive function was assessed at baseline and 2 or 5 years later using the Modified Mini-Mental State Examination. Cognitive impairment was defined as a decline of at least 1.0 SD (9 points) between baseline and follow-up evaluations. Results: After adjustment for baseline Modified Mini-Mental State Examination scores, demographics, fatfree mass, sleep duration, self-reported health, and diabetes mellitus, older adults in the highest sex-specific tertile of AEE had lower odds of incident cognitive impairment than those in the lowest tertile (odds ratio, 0.09; 95% confidence interval, 0.01-0.79). There was also a significant dose response between AEE and incidence of cognitive impairment (P=.05 for trend over tertiles). Conclusions: These findings indicate that greater AEE may be protective against cognitive impairment in a dose-response manner. The significance of overall activity in contrast to vigorous or light activity should be determined. C1 [Middleton, Laura E.] Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Heart & Stroke Fdn Ctr Stroke Recovery, Toronto, ON M4N 3M5, Canada. [Manini, Todd M.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. [Simonsick, Eleanor M.] NIA, Clin Res Branch, Bethesda, MD 20892 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Barnes, Deborah E.; Yaffe, Kristine] San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA USA. [Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Tylavsky, Frances] Univ Tennessee, Dept Biostat & Epidemiol, Memphis, TN USA. [Brach, Jennifer S.] Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA USA. [Everhart, James E.] NIDDK, Epidemiol & Data Syst Program, Bethesda, MD USA. RP Middleton, LE (reprint author), Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Heart & Stroke Fdn Ctr Stroke Recovery, 2075 Bayview Ave,A421, Toronto, ON M4N 3M5, Canada. EM Middleton_l@hotmail.com RI Middleton, Laura/C-6024-2009 OI Middleton, Laura/0000-0001-8624-3123 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, K01-AG-024069, AG 031155]; National Institutes of Health, National Institute on Aging; National Institute of Diabetes and Digestive and Kidney Diseases; Canadian Institute of Health Research fellowship; National Institute on Aging Claude D. Pepper Center [P30AG028740]; Alzheimer's Association [IIRG-06-27306]; American Federation of Aging Research Paul Beeson Career Development Award [K23 AG026766-01] FX This work was supported by National Institute on Aging (NIA) contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. This research was also supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging, and with additional support from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr Middleton is supported by a Canadian Institute of Health Research fellowship; Dr Manini is supported by grant P30AG028740 from the National Institute on Aging Claude D. Pepper Center; Dr Barnes was supported in part by grant K01-AG-024069 from the National Institute on Aging and grant IIRG-06-27306 from the Alzheimer's Association; Dr Brach is supported in part by a National Institutes on Aging and American Federation of Aging Research Paul Beeson Career Development Award (K23 AG026766-01); and Dr Yaffe is supported in part by NIA grant AG 031155 and an Independent Investigator Award from the Alzheimer's Association. NR 44 TC 59 Z9 62 U1 1 U2 21 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 25 PY 2011 VL 171 IS 14 BP 1251 EP 1257 DI 10.1001/archinternmed.2011.277 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 796WN UT WOS:000293084300007 PM 21771893 ER PT J AU Groeneveld, PW Polsky, D Yang, F Yang, L Epstein, AJ AF Groeneveld, Peter W. Polsky, Daniel Yang, Feifei Yang, Lin Epstein, Andrew J. TI The Impact of New Cardiovascular Device Technology on Health Care Costs SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID THERAPY; DISEASE C1 [Groeneveld, Peter W.; Polsky, Daniel; Yang, Feifei; Yang, Lin; Epstein, Andrew J.] Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Groeneveld, Peter W.; Epstein, Andrew J.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Dept Vet Affairs, Philadelphia, PA USA. [Groeneveld, Peter W.; Epstein, Andrew J.] Pittsburgh Vet Affairs Hlth Care Syst, Pittsburgh, PA USA. [Groeneveld, Peter W.; Polsky, Daniel; Epstein, Andrew J.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Groeneveld, PW (reprint author), Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, 1229 Blockley Hall,423 Serv Dr, Philadelphia, PA 19104 USA. EM petergro@mail.med.upenn.edu FU AHRQ HHS [R01 HS018403, 1R01HS018403]; NHLBI NIH HHS [R01 HL086919, 1R01HL086919, R01 HL086919-03] NR 8 TC 10 Z9 10 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 25 PY 2011 VL 171 IS 14 BP 1289 EP 1291 DI 10.1001/archinternmed.2011.141 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 796WN UT WOS:000293084300016 PM 21518936 ER PT J AU Helfrich, CD Blevins, D Smith, JL Kelly, PA Hogan, TP Hagedorn, H Dubbert, PM Sales, AE AF Helfrich, Christian D. Blevins, Dean Smith, Jeffrey L. Kelly, P. Adam Hogan, Timothy P. Hagedorn, Hildi Dubbert, Patricia M. Sales, Anne E. TI Predicting implementation from organizational readiness for change: a study protocol SO IMPLEMENTATION SCIENCE LA English DT Article ID HEPATITIS PREVENTION SERVICES; CHRONIC LIVER-DISEASE; PRIMARY-CARE; ATYPICAL ANTIPSYCHOTICS; SCHIZOPHRENIA; MODEL; DEPRESSION; CLINICS; RISK; INSTRUMENTS AB Background: There is widespread interest in measuring organizational readiness to implement evidence-based practices in clinical care. However, there are a number of challenges to validating organizational measures, including inferential bias arising from the halo effect and method bias - two threats to validity that, while well-documented by organizational scholars, are often ignored in health services research. We describe a protocol to comprehensively assess the psychometric properties of a previously developed survey, the Organizational Readiness to Change Assessment. Objectives: Our objective is to conduct a comprehensive assessment of the psychometric properties of the Organizational Readiness to Change Assessment incorporating methods specifically to address threats from halo effect and method bias. Methods and Design: We will conduct three sets of analyses using longitudinal, secondary data from four partner projects, each testing interventions to improve the implementation of an evidence-based clinical practice. Partner projects field the Organizational Readiness to Change Assessment at baseline (n = 208 respondents; 53 facilities), and prospectively assesses the degree to which the evidence-based practice is implemented. We will conduct predictive and concurrent validities using hierarchical linear modeling and multivariate regression, respectively. For predictive validity, the outcome is the change from baseline to follow-up in the use of the evidence-based practice. We will use intra-class correlations derived from hierarchical linear models to assess inter-rater reliability. Two partner projects will also field measures of job satisfaction for convergent and discriminant validity analyses, and will field Organizational Readiness to Change Assessment measures at follow-up for concurrent validity (n = 158 respondents; 33 facilities). Convergent and discriminant validities will test associations between organizational readiness and different aspects of job satisfaction: satisfaction with leadership, which should be highly correlated with readiness, versus satisfaction with salary, which should be less correlated with readiness. Content validity will be assessed using an expert panel and modified Delphi technique. Discussion: We propose a comprehensive protocol for validating a survey instrument for assessing organizational readiness to change that specifically addresses key threats of bias related to halo effect, method bias and questions of construct validity that often go unexplored in research using measures of organizational constructs. C1 [Helfrich, Christian D.] VA Puget Sound Healthcare Syst, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Helfrich, Christian D.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Blevins, Dean] Ctr Dis Control & Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Div HIV AIDS Prevent, Atlanta, GA USA. [Kelly, P. Adam] SE Louisiana Vet Hlth Care Network, Res Serv, New Orleans, LA USA. [Smith, Jeffrey L.] VA Mental Hlth Qual Enhancement Res Initiat, N Little Rock, AR USA. [Hogan, Timothy P.] Edward Hines Jr Vet Affairs Hosp, Ctr Management Complex Chron Care, eHlth Qual Enhancement Res Initiat, Hines, IL USA. [Hogan, Timothy P.] Edward Hines Jr Vet Affairs Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL USA. [Hogan, Timothy P.] Loyola Univ, Stritch Sch Med, Program Hlth Serv Res, Chicago, IL 60611 USA. [Hagedorn, Hildi] Minneapolis VA Healthcare Syst, VA Subst Use Disorders Qual Enhancement Res Initi, Minneapolis, MN USA. [Dubbert, Patricia M.] S Cent VA Mental Illness Res Educ & Clin Ctr MIRE, N Little Rock, AR USA. [Dubbert, Patricia M.] S Cent VA Geriatr Res Educ & Clin Ctr GRECC, N Little Rock, AR USA. [Sales, Anne E.] VA Inpatient Evaluat Ctr, Cincinnati, OH USA. [Sales, Anne E.] VA Hlth Serv Res & Dev Ctr Excellence, Ann Arbor, MI USA. RP Helfrich, CD (reprint author), VA Puget Sound Healthcare Syst, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. EM christian.helfrich@va.gov RI Sales, Anne/D-9678-2012; Helfrich, Christian/D-2382-2016 OI Helfrich, Christian/0000-0002-9827-4768; Sales, Anne/0000-0001-9360-3334 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [IIR 09-067] FX This study has been funded by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, project grant number IIR 09-067. We wish to thank Rachel Orlando and Penny White for project support for this research study. The views expressed in this article are the authors' and do not necessarily reflect the position or policy of the US Department of Veterans Affairs. NR 80 TC 10 Z9 10 U1 7 U2 29 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD JUL 22 PY 2011 VL 6 AR 76 DI 10.1186/1748-5908-6-76 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 808MU UT WOS:000293982600001 PM 21777479 ER PT J AU Dey, N Das, F Mariappan, MM Mandal, CC Ghosh-Choudhury, N Kasinath, BS Choudhury, GG AF Dey, Nirmalya Das, Falguni Mariappan, Meenalakshmi M. Mandal, Chandi Charan Ghosh-Choudhury, Nandini Kasinath, Balakuntalam S. Choudhury, Goutam Ghosh TI MicroRNA-21 Orchestrates High Glucose-induced Signals to TOR Complex 1, Resulting in Renal Cell Pathology in Diabetes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA TRANSLATION; INDUCED COLLAGEN EXPRESSION; GROWTH-FACTOR-BETA; MESANGIAL CELLS; FIBRONECTIN EXPRESSION; SUPEROXIDE-DISMUTASE; EPITHELIAL-CELLS; PROTEIN-SYNTHESIS; MAMMALIAN TARGET; TRANSGENIC MICE AB Hyperglycemia induces a wide array of signaling pathways in the kidney that lead to hypertrophy and matrix expansion, eventually culminating in progressive kidney failure. High glucose-induced reduction of the tumor suppressor protein phosphatase and tensin homolog deleted in chromosome 10 (PTEN) contributes to renal cell hypertrophy and matrix expansion. We identified microRNA-21 (miR-21) as the molecular link between high glucose and PTEN suppression. Renal cortices from OVE26 type 1 diabetic mice showed significantly elevated levels of miR-21 associated with reduced PTEN and increased fibronectin content. In renal mesangial cells, high glucose increased the expression of miR-21, which targeted the 3'-UTR of PTEN mRNA to inhibit PTEN protein expression. Overexpression of miR-21 mimicked the action of high glucose, which included a reduction in PTEN expression and a concomitant increase in Akt phosphorylation. In contrast, expression of miR-21 Sponge, to inhibit endogenous miR-21, prevented down-regulation of PTEN and phosphorylation of Akt induced by high glucose. Interestingly, high glucose-stimulated miR-21 inactivated PRAS40, a negative regulator of TORC1. Finally, miR-21 enhanced high glucose-induced TORC1 activity, resulting in renal cell hypertrophy and fibronectin expression. Thus, our results identify a previously unrecognized function of miR-21 that is the reciprocal regulation of PTEN levels and Akt/TORC1 activity that mediate critical pathologic features of diabetic kidney disease. C1 [Dey, Nirmalya; Das, Falguni; Mariappan, Meenalakshmi M.; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Mandal, Chandi Charan; Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Vet Affairs Res, San Antonio, TX USA. [Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu FU National Institutes of Health [RO1 DK50190, RO1 AR52425, DK077295, RC2A 036613]; Juvenile Diabetes Research Foundation [1-2008-185]; Veterans Affairs; Cancer Therapy and Research Center, San Antonio, TX; Veterans Affairs Research Service FX This work was supported, in whole or in part, by National Institutes of Health Grants RO1 DK50190 (to G. G. C.), RO1 AR52425 (to N. G. C.), and DK077295 and RC2A 036613 (to B. S. K.). This work was also supported by Juvenile Diabetes Research Foundation Grant 1-2008-185 (to G. G. C.).; Supported by a Veterans Affairs merit review grant and a Ronald P. Williams Orthopedic Oncology Developmental Research Award from the Cancer Therapy and Research Center, San Antonio, TX.; Supported by a grant from the Veterans Affairs Research Service. NR 81 TC 92 Z9 101 U1 0 U2 5 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 JUL 22 PY 2011 VL 286 IS 29 BP 25586 EP 25603 DI 10.1074/jbc.M110.208066 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 796SS UT WOS:000293073000021 PM 21613227 ER PT J AU Tokhtaeva, E Sachs, G Souda, P Bassilian, S Whitelegge, JP Shoshani, L Vagin, O AF Tokhtaeva, Elmira Sachs, George Souda, Puneet Bassilian, Sara Whitelegge, Julian P. Shoshani, Liora Vagin, Olga TI Epithelial Junctions Depend on Intercellular Trans-interactions between the Na,K-ATPase beta(1) Subunits SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CANINE KIDNEY-CELLS; E-CADHERIN; TIGHT JUNCTIONS; ADHESION; GLYCOSYLATION; ANKYRIN; ATPASE; IDENTIFICATION; NA+,K+-ATPASE; ORGANIZATION AB N-Glycans of the Na,K-ATPase beta(1) subunit are important for intercellular adhesion in epithelia, suggesting that epithelial junctions depend on N-glycan-mediated interactions between the beta(1) subunits of neighboring cells. The level of co-immunoprecipitation of the endogenous beta(1) subunit with various YFP-linked beta(1) subunits expressed in Madin-Darby canine kidney cells was used to assess beta(1)-beta(1) interactions. The amount of co-precipitated endogenous dog beta(1) was greater with dog YFP-beta(1) than with rat YFP-beta(1), showing that amino acid-mediated interactions are important for beta(1)-beta(1) binding. Co-precipitation of beta(1) was also less with the unglycosylated YFP-beta(1) than with glycosylated YFP-beta(1), indicating a role for N-glycans. Mixing cells expressing dog YFP-beta(1) with non-transfected cells increased the amount of co-precipitated beta(1), confirming the presence of intercellular (YFP-beta(1))-beta(1) complexes. Accordingly, disruption of intercellular junctions decreased the amount of co-precipitated beta(1) subunits. The decrease in beta(1) co-precipitation both with rat YFP-beta(1) and unglycosylated YFP-beta(1) was associated with decreased detergent stability of junctional proteins and increased paracellular permeability. Reducing N-glycan branching by specific inhibitors increased (YFP-beta(1))-beta(1) co-precipitation and strengthened intercellular junctions. Therefore, interactions between the beta(1) subunits of neighboring cells maintain integrity of intercellular junctions, and alterations in the beta(1) subunit N-glycan structure can regulate stability and tightness of intercellular junctions. C1 [Tokhtaeva, Elmira; Sachs, George; Bassilian, Sara; Vagin, Olga] Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. [Tokhtaeva, Elmira; Sachs, George; Bassilian, Sara; Vagin, Olga] Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. [Souda, Puneet; Whitelegge, Julian P.] Univ Calif Los Angeles, NPI Semel Inst, Pasarow Mass Spectrometry Lab, Los Angeles, CA 90024 USA. [Shoshani, Liora] IPN, CINVESTAV, Dept Physiol Biophys & Neurosci, Mexico City 07360, DF, Mexico. RP Vagin, O (reprint author), VAGLAHS W Los Angeles, 11301 Wilshire Blvd,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. EM olgav@ucla.edu FU National Institutes of Health [DK077149, DK058333]; National Institutes of Health-NCRR [S10 RR023045] FX This work was supported, in whole or in part, by National Institutes of Health Grants DK077149 and DK058333.; We thank Dr. Glenn Nagami (UCLA) and Dr. Ralf Jacob (Marburg University) for careful reading of the manuscript and helpful suggestions. The LTQ-FT was purchased with National Institutes of Health-NCRR support from Grant S10 RR023045. NR 31 TC 16 Z9 16 U1 0 U2 2 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 JUL 22 PY 2011 VL 286 IS 29 BP 25801 EP 25812 DI 10.1074/jbc.M111.252247 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 796SS UT WOS:000293073000042 PM 21642423 ER PT J AU Zhao, W Varghese, M Yemul, S Pan, Y Cheng, A Marano, P Hassan, S Vempati, P Chen, F Qian, XJ Pasinetti, GM AF Zhao, Wei Varghese, Merina Yemul, Shrishailam Pan, Yong Cheng, Alice Marano, Paul Hassan, Sadiq Vempati, Prashant Chen, Fei Qian, Xianjuan Pasinetti, Giulio M. TI Peroxisome proliferator activator receptor gamma coactivator-1alpha (PGC-1 alpha) improves motor performance and survival in a mouse model of amyotrophic lateral sclerosis SO MOLECULAR NEURODEGENERATION LA English DT Article ID NEURON DEGENERATION; TRANSGENIC MICE; MITOCHONDRIAL DYSFUNCTION; 3-NITROPROPIONIC ACID; HUNTINGTONS-DISEASE; AXONAL-TRANSPORT; PROTEIN-KINASE; ALS; NEURODEGENERATION; INHIBITION AB Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects spinal cord and cortical motor neurons. An increasing amount of evidence suggests that mitochondrial dysfunction contributes to motor neuron death in ALS. Peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC-1 alpha) is a principal regulator of mitochondrial biogenesis and oxidative metabolism. Results: In this study, we examined whether PGC-1 alpha plays a protective role in ALS by using a double transgenic mouse model where PGC-1 alpha is over-expressed in an SOD1 transgenic mouse (TgSOD1-G93A/PGC-1 alpha). Our results indicate that PGC-1 alpha significantly improves motor function and survival of SOD1-G93A mice. The behavioral improvements were accompanied by reduced blood glucose level and by protection of motor neuron loss, restoration of mitochondrial electron transport chain activities and inhibition of stress signaling in the spinal cord. Conclusion: Our results demonstrate that PGC-1 alpha plays a beneficial role in a mouse model of ALS, suggesting that PGC-1 alpha may be a potential therapeutic target for ALS therapy. C1 [Zhao, Wei; Varghese, Merina; Yemul, Shrishailam; Pan, Yong; Cheng, Alice; Marano, Paul; Hassan, Sadiq; Vempati, Prashant; Chen, Fei; Qian, Xianjuan; Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Zhao, Wei; Varghese, Merina; Yemul, Shrishailam; Pan, Yong; Cheng, Alice; Vempati, Prashant; Chen, Fei; Qian, Xianjuan; Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, GRECC, Bronx, NY 10468 USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, New York, NY USA. EM giulio.pasinetti@mssm.edu NR 34 TC 48 Z9 48 U1 2 U2 11 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 JUL 19 PY 2011 VL 6 AR 51 DI 10.1186/1750-1326-6-51 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 808AB UT WOS:000293943800001 PM 21771318 ER PT J AU Kwon, S Dong, ZM Wu, PC AF Kwon, Steve Dong, Zhao Ming Wu, Peter C. TI Sentinel lymph node biopsy for high-risk cutaneous squamous cell carcinoma: clinical experience and review of literature SO WORLD JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE sentinel lymph node; squamous cell carcinoma; cutaneous; staging ID EARLY-STAGE MELANOMA; EPIDERMOLYSIS-BULLOSA; PROGNOSTIC-FACTORS; MULTICENTER TRIAL; BREAST-CANCER; SKIN; LYMPHADENECTOMY; VALIDATION; NECK; DISSECTION AB High-risk cutaneous squamous cell carcinoma (SCC) is associated with an increased risk of metastases. The role of sentinel lymph node (SLN) biopsy in these patients remains unclear. To address this uncertainty, we collected clinical data on six patients with clinical N0 high-risk SCC that underwent SLN biopsy between 1999 and 2006 and performed a literature review of SLN procedures for SCC to study the utility of SLN biopsy. There were no positive SLN identified among six cases and there was one local and one distant recurrence on follow-up. Literature review identified 130 reported cases of SLN biopsy for SCC. The SLN positivity rate was 14.1%, 10.1%, and 18.6%; false negative rate was 15.4%, 0%, and 22.2%; and the negative predictive value was 97.8%, 100%, and 95.2% for all sites, head/neck, and truncal/extremity sites, respectively. SLN biopsy remains an investigational staging tool in clinically node-negative high-risk SCC patients. The higher false negative rate and lower negative predictive value among SCC of the trunk/extremity compared to SCC of the head/neck sites suggests a more cautious approach when treating patients with the former. Given the paucity of long-term follow up, an emphasis is placed upon the need for close surveillance regardless of SLN status. C1 [Kwon, Steve; Wu, Peter C.] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Dong, Zhao Ming] VA Puget Sound Hlth Care Syst, Dept Pathol, Seattle, WA USA. [Wu, Peter C.] VA Puget Sound Hlth Care Syst, Dept Surg, Seattle, WA USA. RP Wu, PC (reprint author), Univ Washington, Dept Surg, Seattle, WA 98195 USA. EM pcwu@uw.edu NR 40 TC 26 Z9 28 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1477-7819 J9 WORLD J SURG ONCOL JI World J. Surg. Oncol. PD JUL 19 PY 2011 VL 9 AR 80 DI 10.1186/1477-7819-9-80 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 808HB UT WOS:000293967200002 PM 21771334 ER PT J AU Abrams, TE Vaughan-Sarrazin, M Fan, VS Kaboli, PJ AF Abrams, Thad E. Vaughan-Sarrazin, Mary Fan, Vincent S. Kaboli, Peter J. TI Geographic Isolation and the Risk for Chronic Obstructive Pulmonary Disease-Related Mortality SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-LIFE; HOSPITAL MORTALITY; 30-DAY MORTALITY; FUEL COMBUSTION; HEART-FAILURE; BIOMASS SMOKE; HEALTH; VETERANS; CARE AB Background: Little is known about the possible differences in outcomes between patients with chronic obstructive pulmonary disease (COPD) who live in rural areas and those who live in urban areas of the United States. Objective: To determine whether COPD-related mortality is higher in persons living in rural areas, and to assess whether hospital characteristics influence any observed associations. Design: Retrospective cohort study. Setting: 129 acute care Veterans Affairs hospitals. Patients: Hospitalized patients with a COPD exacerbation. Measurements: Patient rurality (primary exposure); 30-day mortality (primary outcome); and hospital volume and hospital rurality, defined as the mean proportion of hospital admissions coming from rural areas (secondary exposures). Results: 18 809 patients (71% of the study population) lived in urban areas, 5671 (21%) in rural areas, and 1919 (7%) in isolated rural areas. Mortality was increased in patients living in isolated rural areas compared with urban areas (5.0% vs. 3.8%; P = 0.002). The increase in mortality associated with living in an isolated rural area persisted after adjustment for patient characteristics and hospital rurality and volume (odds ratio [OR], 1.42 [95% CI, 1.07 to 1.89]; P = 0.016). Adjusted mortality did not seem to be higher in patients living in nonisolated rural areas (OR, 1.09 [CI, 0.90 to 1.32]; P = 0.47). Results were unchanged in analyses assessing the influence of an omitted confounder on estimates. Limitations: The study population was limited to mostly male inpatients who were veterans. Results were based on administrative data. Conclusion: Patients with COPD living in isolated rural areas of the United States seem to be at greater risk for COPD exacerbation-related mortality than those living in urban areas, independent of hospital rurality and volume. Mortality was not increased for patients living in nonisolated rural areas. C1 [Abrams, Thad E.] Iowa City Vet Affairs Healthcare Syst, Vet Rural Hlth Resource Center Cent Reg, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City Vet Affairs Med Ctr,Vet Hlth Adm Off Ru, Iowa City, IA 52246 USA. Univ Iowa, Iowa City, IA USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP Abrams, TE (reprint author), Iowa City Vet Affairs Healthcare Syst, Vet Rural Hlth Resource Center Cent Reg, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City Vet Affairs Med Ctr,Vet Hlth Adm Off Ru, 601 Highway 6 W,Mailstop 152, Iowa City, IA 52246 USA. EM Thad-Abrams@va.gov FU Veterans Health Administration Office of Rural Health; Veterans Rural Health Resource Center-Central Region; Health Services Research and Development Service through the Center for Comprehensive Access and Delivery Research and Evaluation at the Iowa City Veterans Affairs Healthcare System, U. S. Department of Veterans Affairs [HFP 04-149] FX By the Veterans Health Administration Office of Rural Health, Veterans Rural Health Resource Center-Central Region, and the Health Services Research and Development Service, through the Center for Comprehensive Access and Delivery Research and Evaluation at the Iowa City Veterans Affairs Healthcare System, U. S. Department of Veterans Affairs (grant HFP 04-149). NR 0 TC 14 Z9 14 U1 0 U2 6 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 19 PY 2011 VL 155 IS 2 BP 80 EP + DI 10.7326/0003-4819-155-2-201107190-00003 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 793KW UT WOS:000292822000014 PM 21768581 ER PT J AU Williams, BA Sudore, RL Greifinger, R Morrison, RS AF Williams, Brie A. Sudore, Rebecca L. Greifinger, Robert Morrison, R. Sean TI Balancing Punishment and Compassion for Seriously III Prisoners SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID PALLIATIVE CARE; LIFE; DISABILITY; END AB Compassionate release is a program that allows some eligible, seriously ill prisoners to die outside of prison before sentence completion. It became a matter of federal statute in 1984 and has been adopted by most U. S. prison jurisdictions. Incarceration is justified on 4 principles: retribution, rehabilitation, deterrence, and incapacitation. Compassionate release derives from the theory that changes in health status may affect these principles and thus alter justification for incarceration and sentence completion. The medical profession is intricately involved in this process because eligibility for consideration for compassionate release is generally based on medical evidence. Many policy experts are calling for broader use of compassionate release because of many factors, such as an aging prison population, overcrowding, the increasing deaths in custody, and the soaring medical costs of the criminal justice system. Even so, the medical eligibility criteria of many compassionate-release guidelines-which often assume a definitive prognosis-are clinically flawed, and procedural barriers may further limit their rational application. We propose changes to address these flaws. C1 [Williams, Brie A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA USA. CUNY, Mt Sinai Sch Med, John Jay Coll Criminal Justice, New York, NY 10021 USA. Natl Palliat Care Res Ctr, New York, NY USA. James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Williams, BA (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement St,Box 181-G, San Francisco, CA 94121 USA. EM brie.williams@ucsf.edu FU Brookdale Leadership in Aging Fellowship; National Institute on Aging [K23AG033102, K24 AG022345]; National Palliative Care Research Center; Pfizer FX By a grant from the Brookdale Leadership in Aging Fellowship and the National Institute on Aging (K23AG033102) (Dr. Williams), from Mid-Career-Investigator Award in Patient-Oriented Research from the National Institute on Aging (K24 AG022345) and the National Palliative Care Research Center (Dr. Morrison), and a Pfizer Fellowship in Clear Health Communication (Dr. Sudore). NR 0 TC 13 Z9 13 U1 3 U2 18 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 19 PY 2011 VL 155 IS 2 BP 122 EP 126 DI 10.7326/0003-4819-155-2-201107190-00348 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 793KW UT WOS:000292822000019 PM 21628351 ER PT J AU Bansal, N Hsu, CY Zhao, SJ Whooley, MA Ix, JH AF Bansal, Nisha Hsu, Chi-yuan Zhao, Shoujun Whooley, Mary A. Ix, Joachim H. TI Relation of Body Mass Index to Urinary Creatinine Excretion Rate in Patients With Coronary Heart Disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; LEFT-VENTRICULAR HYPERTROPHY; ARTERY-DISEASE; HEMODIALYSIS-PATIENTS; NUTRITIONAL-STATUS; PROGNOSTIC VALUE; CYSTATIN-C; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; ALL-CAUSE AB In patients with prevalent coronary heart disease (CHD), studies have found a paradoxical relation in that patients with higher body mass indexes (BMIs) have lower mortality. One possibility is that patients with higher BMIs have greater muscle mass, and higher BMI may be a marker of better overall health status. The aim of this study was to evaluate whether the paradoxical association of BMI with mortality in patients with CHD is attenuated when accounting for urinary creatinine excretion, a marker of muscle mass. The Heart and Soul Study is an observational study of outpatients with stable CHD. Outpatient 24-hour timed urine collections were obtained. Participants were followed up for death for 5.9 +/- 1.9 years. Cox proportional-hazards models were used to evaluate the association between gender-specific BMI quintiles and mortality. There were 886 participants in the study population. Participants in higher quintiles of BMI were younger, were more likely to have diabetes mellitus and hypertension, and had higher urinary creatinine excretion rate. Compared to the lowest BMI quintile, subjects in higher BMI quintiles were less likely to die during follow-up. Adjustment for major demographic variables, traditional cardiovascular risk factors, and kidney function did not attenuate the relation. Additional adjustment for urinary creatinine excretion rate did not materially change the association between BMI and all-cause mortality. In conclusion, low muscle mass and low BMI are each associated with greater all-cause mortality, but low muscle mass does not appear to explain why CHD patients with low BMIs have worse prognosis. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:179-184) C1 [Bansal, Nisha; Hsu, Chi-yuan; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94112 USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Zhao, Shoujun; Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Family & Preventat Med, Div Prevent Med, San Diego, CA 92103 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Dept Med, Nephrol Sect, San Diego, CA USA. RP Bansal, N (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94112 USA. EM nisha.bansal@ucsf.edu FU American Kidney Fund, Rockville, Maryland; National Heart, Lung, and Blood Institute, Bethesda, Maryland [1R01HL096851]; American Heart Association, Dallas, Texas; National Institute of Diabetes and Digestive and Kidney Diseases [1 K23DK088865]; United States Department of Veterans Affairs, Washington, District of Columbia; American Federation for Aging Research, New York, New York; Robert Wood Johnson Foundation, Princeton, New Jersey; Nancy Kirwan Heart Research Fund, San Francisco, California; Ischemia Research and Education Foundation, San Bruno, California; National Heart, Lung, and Blood Institute [R01 HL079235] FX This study was supported by a grant from the American Kidney Fund, Rockville, Maryland, to Dr. Bansal; Grant 1R01HL096851 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland, to Dr. Ix; and a Fellow-to-Faculty Transition Award from the American Heart Association, Dallas, Texas, to Dr. Ix. The study was also supported by Grant 1 K23DK088865 from the National Institute of Diabetes and Digestive and Kidney Diseases to Dr. Bansal. The Heart and Soul Study was funded by the United States Department of Veterans Affairs, Washington, District of Columbia; the American Federation for Aging Research, New York, New York; the Robert Wood Johnson Foundation, Princeton, New Jersey; the Nancy Kirwan Heart Research Fund, San Francisco, California; the Ischemia Research and Education Foundation, San Bruno, California; and Grant R01 HL079235 from the National Heart, Lung, and Blood Institute. NR 29 TC 4 Z9 5 U1 0 U2 3 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 JUL 15 PY 2011 VL 108 IS 2 BP 179 EP 184 DI 10.1016/j.amjcard.2011.03.020 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 809DH UT WOS:000294031500002 PM 21529727 ER PT J AU Sun, HY Singh, N AF Sun, Hsin-Yun Singh, Nina TI Opportunistic Infection-Associated Immune Reconstitution Syndrome in Transplant Recipients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID REGULATORY T-CELLS; INFLAMMATORY SYNDROME IRIS; VERSUS-HOST-DISEASE; CRYPTOCOCCAL MENINGITIS; CEREBROSPINAL-FLUID; CORTICOSTEROID-THERAPY; LIVER-TRANSPLANTATION; CALCINEURIN INHIBITOR; INTERLEUKIN-12 FAMILY; PARADOXICAL RESPONSE AB Reversal of pathogen-induced immunosuppression upon employment of effective antimicrobial therapy and withdrawal of iatrogenic immunosuppression has the potential to shift the host immune repertoire towards pathologic inflammatory responses conducive to immune reconstitution syndrome (IRS). Posttransplant IRS has been observed with fungi, M. tuberculosis, cytomegalovirus, and polyoma virus nephropathy. This review discusses the existing state of knowledge regarding IRS and the immune mechanisms that underlie its pathogenesis, with significant implications for developing reliable diagnostic biomarkers and optimal management strategies for post-transplant opportunistic infection-associated IRS. C1 [Sun, Hsin-Yun; Singh, Nina] VA Pittsburgh Healthcare Syst, Infect Dis Sect, Pittsburgh, PA USA. [Singh, Nina] Univ Pittsburgh, Pittsburgh, PA USA. [Sun, Hsin-Yun] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Sun, Hsin-Yun] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. RP Singh, N (reprint author), VA Med Ctr, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. EM nis5@pitt.edu OI SUN, HSIN-YUN/0000-0003-0074-7721 FU Pfizer FX N. S. has received investigator-initiated research support from Pfizer. H.-Y. S.: No reported conflicts. NR 101 TC 30 Z9 30 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 15 PY 2011 VL 53 IS 2 BP 168 EP 176 DI 10.1093/cid/cir276 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 796BA UT WOS:000293024000011 PM 21690625 ER PT J AU Mann, SL Hazlett, EA Byne, W Hof, PR Buchsbaum, MS Cohen, BH Goldstein, KE Haznedar, MM Mitsis, EM Siever, LJ Chu, KW AF Mann, Sarah L. Hazlett, Erin A. Byne, William Hof, Patrick R. Buchsbaum, Monte S. Cohen, Barry H. Goldstein, Kim E. Haznedar, M. Mehmet Mitsis, Effie M. Siever, Larry J. Chu, King-Wai TI Anterior and posterior cingulate cortex volume in healthy adults: Effects of aging and gender differences SO BRAIN RESEARCH LA English DT Article DE Cingulate cortex; Aging; Gender differences; MRI; Gray matter; Morphometry ID COMORBIDITY SURVEY REPLICATION; AGE-RELATED DIFFERENCES; GRAY-MATTER VOLUME; SEX-DIFFERENCES; CEREBRAL-CORTEX; BRAIN STRUCTURE; MEMORY PERFORMANCE; ALZHEIMER-DISEASE; SIGNAL INTENSITY; BIPOLAR DISORDER AB The cingulate cortex frequently shows gray matter loss with age as well as gender differences in structure and function, but little is known about whether individual cingulate Brodmann areas show gender-specific patterns of age-related volume decline. This study examined age-related changes, gender differences, and the interaction of age and gender in the relative volume of cingulate gray matter in areas 25, 24, 31, 23, and 29, over seven decades of adulthood. Participants included healthy, age-matched men and women, aged 20-87 (n=70). Main findings were as follows: (1) The whole cingulate showed significant age-related volume declines (averaging 5.54% decline between decades, 20s-80s). Each of the five cingulate areas also showed a significant decline with age, and individual areas showed different patterns of decline across the decades: Smaller volume with age was most evident in area 31, followed by 25 and 24. (2) Women had relatively larger cingulate gray matter volume than men overall and in area 24. (3) Men and women showed different patterns of age-related volume decline in area 31, at midlife and late in life. By delineating normal gender differences and age-related morphometric changes in the cingulate cortex over seven decades of adulthood, this study improves the baseline for comparison with structural irregularities in the cingulate cortex associated with psychopathology. The Brodmann area-based approach also facilitates comparisons across studies that aim to draw inferences between age- and gender-related structural differences in the cingulate gyrus and corresponding differences in cingulate function. Published by Elsevier B.V. C1 [Hazlett, Erin A.; Byne, William; Haznedar, M. Mehmet; Siever, Larry J.; Chu, King-Wai] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY 10468 USA. [Mann, Sarah L.; Hazlett, Erin A.; Byne, William; Goldstein, Kim E.; Haznedar, M. Mehmet; Mitsis, Effie M.; Siever, Larry J.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Hof, Patrick R.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Buchsbaum, Monte S.] Univ Calif San Diego, Dept Psychiat & Radiol, La Jolla, CA 92093 USA. [Cohen, Barry H.] NYU, Dept Psychol, New York, NY 10003 USA. RP Hazlett, EA (reprint author), James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, 130 W Kingsbridge Rd,Room 6A-45, Bronx, NY 10468 USA. EM erin.hazlett@mssm.edu FU Charles A. Dana Foundation; NIMH [MH073911]; VISN 3 Mental Illness Research, Education, and Clinical Center, Department of Veterans Affairs FX The collection of the MRI data was supported by a grant from the Charles A. Dana Foundation to Drs. Mohs and Buchsbaum. This research was supported in part by a NIMH grant to Dr. Hazlett (MH073911) and the VISN 3 Mental Illness Research, Education, and Clinical Center, Department of Veterans Affairs. NR 90 TC 19 Z9 22 U1 3 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 15 PY 2011 VL 1401 BP 18 EP 29 DI 10.1016/j.brainres.2011.05.050 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 794ZN UT WOS:000292941400003 PM 21669408 ER PT J AU Habib, SL AF Habib, Samy L. TI Tuberin and mTOR A key apoptotic pathway in diabetes SO CELL CYCLE LA English DT Editorial Material ID TUBULAR EPITHELIAL-CELLS; MOLECULE BAD; EXPRESSION; GLUCOSE C1 Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, S Texas Vet Healthcare Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Habib, SL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, S Texas Vet Healthcare Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. EM habib@uthscsa.edu NR 10 TC 3 Z9 3 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 JUL 15 PY 2011 VL 10 IS 14 BP 2237 EP 2238 DI 10.4161/cc.10.14.15849 PG 2 WC Cell Biology SC Cell Biology GA 792ST UT WOS:000292770400001 PM 21673498 ER PT J AU Baldys, A Raymond, JR AF Baldys, Aleksander Raymond, John R. TI Role of c-Cbl Carboxyl Terminus in Serotonin 5-HT2A Receptor Recycling and Resensitization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTOR; INDEPENDENT INTERNALIZATION; DOWN-REGULATION; TRAFFICKING; ENDOCYTOSIS; UBIQUITINATION; HRS; DEGRADATION; ENDOSOMES; MECHANISM AB The 5-hydroxytryptamine 2A receptor (5-HT2AR) undergoes constitutive and agonist-dependent internalization. Despite many advances in our understanding of G protein-coupled receptor trafficking, the exact mechanism of endocytic sorting of G protein-coupled receptors remains obscure. Recently, we have reported a novel finding documenting a global role for the ubiquitin ligase c-Cbl in regulating vesicular sorting of epidermal growth factor receptor (Baldys, A., Gooz, M., Morinelli, T. A., Lee, M. H., Raymond, J. R., Jr., Luttrell, L. M., and Raymond, J. R., Sr. (2009) Biochemistry 48, 1462-1473). Thus, we tested the hypothesis that c-Cbl might play a role in 5-HT2AR recycling. In this study, we demonstrated an association of 5-HT2AR with c-Cbl. Furthermore, down-regulation of c-Cbl by RNA interference blocked efficient recycling of 5-HT2AR to the plasma membrane. Immunofluorescence microscopy revealed that 5-HT2A receptors were trapped in early endosome antigen 1- and Rab11-positive sorting endosomes in cells overexpressing c-Cbl mutants lacking carboxyl termini. This inhibitory effect was associated with a relative decrease in association of c-Cbl truncation proteins with the 5-HT2AR, compared with that observed for the full-length c-Cbl fusion protein. Consistent with the delayed recycling, 5-HT2AR resensitization was greatly attenuated in the presence of c-Cbl mutants lacking carboxyl termini, as detected by changes in the cytosolic calcium. Taken together, these studies have led to the discovery that the C-terminal region of c-Cbl plays a crucial role in the temporal and spatial control of 5-HT2AR recycling. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29425 USA. RP Raymond, JR (reprint author), Med Coll Wisconsin, Off President, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM jraymondj@mcw.edu FU National Institutes of Health [DK052448, GM063909]; Department of Veterans Affairs; American Heart Association; Medical University of South Carolina Division of Nephrology and Dialysis Clinics, Inc. FX This work was supported, in whole or in part, by National Institutes of Health Grants DK052448 and GM063909 (to J. R. R.), Department of Veterans Affairs Merit and Research Enhancement Award Program grants (to J. R. R.), a American Heart Association (Mid-Atlantic) fellowship (to A. B.), and laboratory endowments jointly supported by the Medical University of South Carolina Division of Nephrology and Dialysis Clinics, Inc. (to J. R. R.). NR 28 TC 1 Z9 1 U1 0 U2 0 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 JUL 15 PY 2011 VL 286 IS 28 BP 24656 EP 24665 DI 10.1074/jbc.M110.119891 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 789WD UT WOS:000292547900016 PM 21464131 ER PT J AU Rahmaniyan, M Curley, RW Obeid, LM Hannun, YA Kraveka, JM AF Rahmaniyan, Mehrdad Curley, Robert W. Obeid, Lina M. Hannun, Yusuf A. Kraveka, Jacqueline M. TI Identification of Dihydroceramide Desaturase as a Direct in Vitro Target for Fenretinide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID METABOLITE 4-OXO-FENRETINIDE; IRREVERSIBLE INHIBITION; ORAL FENRETINIDE; BREAST-CANCER; CELL-DEATH; CERAMIDE; SPHINGOLIPIDS; APOPTOSIS; CHEMOPREVENTION; BIOSYNTHESIS AB The dihydroceramide desaturase (DES) enzyme is responsible for inserting the 4,5-trans-double bond to the sphingolipid backbone of dihydroceramide. We previously demonstrated that fenretinide (4-HPR) inhibited DES activity in SMS-KCNR neuroblastoma cells. In this study, we investigated whether 4-HPR acted directly on the enzyme in vitro. N-C8:0-D-erythro-dihydroceramide (C-8-dhCer) was used as a substrate to study the conversion of dihydroceramide into ceramide in vitro using rat liver microsomes, and the formation of tritiated water after the addition of the tritiated substrate was detected and used to measure DES activity. NADH served as a cofactor. The apparent K-m for C-8-dhCer and NADH were 1.92 +/- 0.36 mu M and 43.4 +/- 6.47 mu M, respectively; and the V-max was 3.16 +/- 0.24 and 4.11 +/- 0.18 nmol/min/g protein. Next, the effects of 4-HPR and its metabolites on DES activity were investigated. 4-HPR was found to inhibit DES in a dose-dependent manner. At 20 min, the inhibition was competitive; however, longer incubation times demonstrated the inhibition to be irreversible. Among the major metabolites of 4-HPR, 4-oxo-N-(4-hydroxyphenyl) retinamide (4-oxo-4-HPR) showed the highest inhibitory effect with substrate concentration of 0.5 mu M, with an IC50 of 1.68 mu M as compared with an IC50 of 2.32 mu M for 4-HPR. N-(4-Methoxyphenyl) retinamide (4-MPR) and 4-Oxo-N-(4-methoxyphenyl) retinamide (4-oxo-4-MPR) had minimal effects on DES activity. A known competitive inhibitor of DES, C-8-cyclopropenylceramide was used as a positive control. These studies define for the first time a direct in vitro target for 4-HPR and suggest that inhibitors of DES may be used as therapeutic interventions to regulate ceramide desaturation and consequent function. C1 [Rahmaniyan, Mehrdad; Kraveka, Jacqueline M.] Med Univ S Carolina, Dept Pediat, Div Hematol Oncol, Charleston, SC USA. [Curley, Robert W.] Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA. [Obeid, Lina M.; Hannun, Yusuf A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Obeid, Lina M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Kraveka, JM (reprint author), Med Univ S Carolina, Dept Pediat Hematol Oncol, 135 Rutledge Ave,MSC 558, Charleston, SC 29425 USA. EM kravekjm@musc.edu OI obeid, lina/0000-0002-0734-0847 FU National Institutes of Health [K01-CA100767, P01-CA97132, R01-AG016583, R01-CA49837, C06-RR018823]; Office of Research and Development; Department of Veterans Affairs; Ralph H. Johnson VA Medical Center (Charleston, SC) from the National Center for Research Resources [P20-RR17677]; Rally Foundation for Childhood Cancer Research; Monica Kreber Golf Tournament; Chase After a Cure Foundation; Hyundai Hope on Wheels FX This work was supported, in whole or in part, by National Institutes of Health Grants K01-CA100767 (to J. M. K.), P01-CA97132 (to Y. A. H. and L. M. O.), R01-AG016583 (to L. M. O.), R01-CA49837 (to R. W. C.), C06-RR018823 (Lipidomics Core), and by a MERIT award by the Office of Research and Development (to L. M. O.). This work was also supported by the Department of Veterans Affairs, Ralph H. Johnson VA Medical Center (Charleston, SC) by Grant P20-RR17677 from the National Center for Research Resources and by grants from the Rally Foundation for Childhood Cancer Research, the Monica Kreber Golf Tournament, the Chase After a Cure Foundation, and Hyundai Hope on Wheels (to J. M. K.). NR 41 TC 36 Z9 37 U1 0 U2 0 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 JUL 15 PY 2011 VL 286 IS 28 BP 24754 EP 24764 DI 10.1074/jbc.M111.250779 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 789WD UT WOS:000292547900026 PM 21543327 ER PT J AU Yuan, KY Jing, G Chen, JF Liu, H Zhang, K Li, YB Wu, H McDonald, JM Chen, YB AF Yuan, Kaiyu Jing, Gu Chen, Jianfeng Liu, Hui Zhang, Kui Li, Yuebin Wu, Hui McDonald, Jay M. Chen, Yabing TI Calmodulin Mediates Fas-induced FADD-independent Survival Signaling in Pancreatic Cancer Cells via Activation of Src-Extracellular Signal-regulated Kinase (ERK) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; GASTROINTESTINAL TUMOR-CELLS; DEATH DOMAIN PROTEIN; INDUCED APOPTOSIS; CHOLANGIOCARCINOMA CELLS; INHIBITORY PROTEIN; GROWTH-FACTORS; IMMUNE-SYSTEM; CD95 LIGAND; PROLIFERATION AB Pancreatic cancer remains a devastating malignancy with a poor prognosis and is largely resistant to current therapies. To understand the resistance of pancreatic tumors to Fas death receptor-induced apoptosis, we investigated the molecular mechanisms of Fas-activated survival signaling in pancreatic cancer cells. We found that knockdown of the Fas-associated protein with death domain (FADD), the adaptor that mediates downstream signaling upon Fas activation, rendered Fas-sensitive MiaPaCa-2 and BxPC-3 pancreatic cells resistant to Fas-induced apoptosis. By contrast, Fas activation promoted the survival of the FADD knockdown MiaPaCa-2 and BxPC-3 cells in a concentration-dependent manner. The pharmacological inhibitor of ERK, PD98059, abrogated Fas-promoted cell survival in FADD knockdown MiaPaCa-2 and BxPC-3 cells. Furthermore, increased phosphorylation of Src was demonstrated to mediate Fas-induced ERK activation and cell survival. Immunoprecipitation of Fas in the FADD knockdown cells identified the presence of increased calmodulin, Src, and phosphorylated Src in the Fas-associated protein complex upon Fas activation. Trifluoperazine, a calmodulin antagonist, inhibited Fas-induced recruitment of calmodulin, Src, and phosphorylated Src. Consistently, trifluoperazine blocked Fas-promoted cell survival. A direct interaction of calmodulin and Src and their binding site were identified with recombinant proteins. These results support an essential role of calmodulin in mediating Fas-induced FADD-independent activation of Src-ERK signaling pathways, which promote survival signaling in pancreatic cancer cells. Understanding the molecular mechanisms responsible for the resistance of pancreatic cells to apoptosis induced by Fas-death receptor signaling may provide molecular insights into designing novel therapies to treat pancreatic tumors. C1 [Yuan, Kaiyu; Jing, Gu; Chen, Jianfeng; McDonald, Jay M.; Chen, Yabing] Univ Alabama, Sch Dent, Dept Pathol, Birmingham, AL 35294 USA. [Liu, Hui] Univ Alabama, Sch Dent, Dept Physiol, Birmingham, AL 35294 USA. [Zhang, Kui] Univ Alabama, Sch Dent, Dept Biostat, Birmingham, AL 35294 USA. [Li, Yuebin; Wu, Hui] Univ Alabama, Sch Dent, Dept Pediat Dent, Birmingham, AL 35294 USA. [Li, Yuebin; Wu, Hui] Univ Alabama, Sch Med, Dept Pediat Dent, Birmingham, AL 35294 USA. [Yuan, Kaiyu; Jing, Gu; Chen, Jianfeng; McDonald, Jay M.; Chen, Yabing] Univ Alabama, Sch Med, Dept Pathol, Birmingham, AL 35294 USA. [Liu, Hui] Univ Alabama, Sch Med, Dept Physiol, Birmingham, AL 35294 USA. [Zhang, Kui] Univ Alabama, Sch Med, Dept Biostat, Birmingham, AL 35294 USA. [McDonald, Jay M.; Chen, Yabing] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Chen, YB (reprint author), Univ Alabama, Sch Dent, Dept Pathol, 710 Shelby Res Bldg,1825 Univ Blvd, Birmingham, AL 35294 USA. EM ybchen@uab.edu FU Department of Pathology, University of Alabama at Birmingham; Veterans Affairs merit review award FX This work was supported in part by start-up funds from the Department of Pathology, University of Alabama at Birmingham (to Y. C.), and a Veterans Affairs merit review award (to J. M. M.). NR 59 TC 20 Z9 21 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 JUL 15 PY 2011 VL 286 IS 28 BP 24776 EP 24784 DI 10.1074/jbc.M110.202804 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 789WD UT WOS:000292547900028 PM 21613217 ER PT J AU Novgorodov, SA Wu, BX Gudz, TI Bielawski, J Ovchinnikova, TV Hannun, YA Obeid, LM AF Novgorodov, Sergei A. Wu, Bill X. Gudz, Tatyana I. Bielawski, Jacek Ovchinnikova, Tatiana V. Hannun, Yusuf A. Obeid, Lina M. TI Novel Pathway of Ceramide Production in Mitochondria THIOESTERASE AND NEUTRAL CERAMIDASE PRODUCE CERAMIDE FROM SPHINGOSINE AND ACYL-CoA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT-LIVER MITOCHONDRIA; PERMEABILITY TRANSITION PORE; RADIATION-INDUCED APOPTOSIS; LONG-CHAIN; SPHINGOLIPID METABOLISM; COA THIOESTERASES; MOLECULAR-CLONING; ENDOPLASMIC-RETICULUM; ENZYMATIC HYDROLYSIS; RESPIRATORY-CHAIN AB Reports suggest that excessive ceramide accumulation in mitochondria is required to initiate the intrinsic apoptotic pathway and subsequent cell death, but how ceramide accumulates is unclear. Here we report that liver mitochondria exhibit ceramide formation from sphingosine and palmitoyl-CoA and from sphingosine and palmitate. Importantly, this activity was markedly decreased in liver from neutral ceramidase (NCDase)-deficient mice. Moreover, the levels of ceramide were dissimilar in liver mitochondria of WT and NCDase KO mice. These results suggest that NCDase is a key participant of ceramide formation in liver mitochondria. We also report that highly purified liver mitochondria have ceramidase, reverse ceramidase, and thioesterase activities. Increased accessibility of palmitoyl-CoA to the mitochondrial matrix with the pore-forming peptide zervamicin IIB resulted in 2-fold increases in palmitoyl-CoA hydrolysis by thioesterase. This increased hydrolysis was accompanied by an increase in ceramide formation, demonstrating that both outer membrane and matrix localized thioesterases can regulate ceramide formation. Also, ceramide formation might occur both in the outer mitochondrial membrane and in the mitochondrial matrix, suggesting the existence of distinct ceramide pools. Taken together, these results suggest that the reverse activity of NCDase contributes to sphingolipid homeostasis in this organelle in vivo. C1 [Novgorodov, Sergei A.; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Gudz, Tatyana I.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Novgorodov, Sergei A.; Wu, Bill X.; Bielawski, Jacek; Hannun, Yusuf A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Gudz, Tatyana I.; Obeid, Lina M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Ovchinnikova, Tatiana V.] Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,MSC779, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU National Institutes of Health [AG16583, CA87584, P20RR17677-04]; Russian Federal Target Program [NK-602P/19, P1159]; Office of Research and Development, Department of Veterans Affairs, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina; National Center for Research Resources [C06 RR018823] FX This work was supported, in whole or in part, by National Institutes of Health Grants AG16583 (to L.M.O.), CA87584 (to Y.A.H.), and P20RR17677-04 (to T.I.G.). This work was also supported by the Russian Federal Target Program "Scientific and Science-Educational Personnel of Innovative Russia" (project NK-602P/19, state contract P1159) (to T.V.O.). This manuscript is based upon work supported in part by a MERIT Awards by the Office of Research and Development, Department of Veterans Affairs, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina (to L.M.O. and T.I.G.).; We thank Kathy Wiita-Fisk for administrative assistance, Stefka Spassieva for critical reading of the manuscript, and Christian Frezza for valuable advice related to isolation of mouse mitochondria. We thank Dr. Richard Proia for generously providing anti-NCDase antibody. We thank Dr. Jennifer G. Schnellmann for help with preparation of the manuscript. Measurement of sphingolipids was conducted by the Lipidomics Core of MUSC in a facility constructed with support from the National Institutes of Health Grant C06 RR018823 from the Extramural Research Facilities Program of the National Center for Research Resources. NR 96 TC 39 Z9 41 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 15 PY 2011 VL 286 IS 28 BP 25352 EP 25362 DI 10.1074/jbc.M110.214866 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 789WD UT WOS:000292547900081 PM 21613224 ER PT J AU Doyle, T Chen, ZM Obeid, LM Salvemini, D AF Doyle, Tim Chen, Zhoumou Obeid, Lina M. Salvemini, Daniela TI Sphingosine-1-phosphate acting via the S1P(1) receptor is a downstream signaling pathway in ceramide-induced hyperalgesia SO NEUROSCIENCE LETTERS LA English DT Article DE Ceramide; Sphingosine-1-phosphate; Sphingosine kinase; Hyperalgesia; Sphingosine-1-phosphate receptor subtype 1 (S1PR(1)) ID RAT SENSORY NEURONS; NERVE GROWTH-FACTOR; MORPHINE ANTINOCICEPTIVE TOLERANCE; SPHINGOSINE KINASE; THERAPEUTIC TARGETS; INFLAMMATORY PAIN; SPINAL CERAMIDE; IN-VIVO; SPHINGOLIPIDS; EXCITABILITY AB Ceramide is a potent pro-inflammatory sphingolipid recently shown to exert potent hyperalgesic responses in rats. Once generated, ceramide is converted by sphingosine kinase (SphK) 1 and/or 2 to one of its active metabolite sphingosine-1-phosphate (SIP), which in turn signals through G-protein coupled S1P receptors. The objectives of this paper were to define whether ceramide-induced hyperalgesia is driven by S1P. Our results show that intraplantar injection of ceramide in rats led to a time-dependent development of thermal hyperalgesia that was associated with an increase in tumor necrosis factor-a (TNF-alpha) in paw tissues. The development of hyperalgesia was significantly attenuated by a soluble TNF receptor I. TNF-alpha is known to activate SphK1, thus SIP production, and our results demonstrate that, the development of hyperalgesia was attenuated in a dose-dependent fashion by a well characterized inhibitor of SphK1 and SphK2 (SK-I) and by a murine monoclonal anti-SI P antibody (LT1002). LT1017, the isotype-matched control monoclonal antibody for LT1002, had no effect. Our results further demonstrate that SIP contributes to the development of hyperalgesia via the SIP receptor 1 subtype (S1PR(1)), since responses were blocked by a well characterized S1PR(1) antagonist, W146, but not by its inactive enantiomer, W140. Collectively, these results provide mechanistic evidence implicating the S1P-to-S1PR(1) pathway as a downstream signaling pathway in ceramide-induced hyperalgesia. Targeting SIP may be a novel therapeutic approach in pain management. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Doyle, Tim; Chen, Zhoumou; Salvemini, Daniela] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA. [Obeid, Lina M.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Salvemini, D (reprint author), St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, 1402 S Grand Blvd, St Louis, MO 63104 USA. EM salvemd@slu.edu OI obeid, lina/0000-0002-0734-0847 FU VA Merit Award [R01 GM062887]; [R01 DA024074]; [R21 DA023056] FX Supported by R01 DA024074 and R21 DA023056 (DS), and VA Merit Award and R01 GM062887 (LO). We would like to thank Amgen (Thousand Oaks, CA) for their kind gift of the soluble TNF receptor I (sTNFR1) and Lpath (San Diego, CA) for their kind gift of the murine monoclonal anti-S1P antibody. LT1002 and LT1017 (isotype-matched control mAb). NR 33 TC 12 Z9 13 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 15 PY 2011 VL 499 IS 1 BP 4 EP 8 DI 10.1016/j.neulet.2011.05.018 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 793EW UT WOS:000292804200002 PM 21605625 ER PT J AU Enestvedt, BK Sonnenberg, A AF Enestvedt, B. K. Sonnenberg, A. TI Practice patterns for achalasia - room for improvement? authors' reply SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Letter ID FATTY LIVER-DISEASE; TRANSIENT ELASTOGRAPHY; STIFFNESS MEASUREMENT; FIBROSIS; DIAGNOSIS; CHINESE C1 [Enestvedt, B. K.] Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR 97201 USA. Portland VA Med Ctr P3 GI, Portland VA Med Ctr, Portland, OR USA. RP Enestvedt, BK (reprint author), Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR 97201 USA. EM sonnenbe@ohsu.edu 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 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD JUL 15 PY 2011 VL 34 IS 2 BP 253 EP 254 DI 10.1111/j.1365-2036.2011.04696.x PG 4 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 784JD UT WOS:000292152300016 ER PT J AU Dombrovski, AY Szanto, K Siegle, GJ Wallace, ML Forman, SD Sahakian, B Reynolds, CF Clark, L AF Dombrovski, Alexandre Y. Szanto, Katalin Siegle, Greg J. Wallace, Meredith L. Forman, Steven D. Sahakian, Barbara Reynolds, Charles F., III Clark, Luke TI Lethal Forethought: Delayed Reward Discounting Differentiates High- and Low-Lethality Suicide Attempts in Old Age SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Aged; choice behavior; cognition; decision making; depressive disorder; executive function; reward; suicide; time perception ID AGGRESSIVE BEHAVIORS; INTERTEMPORAL CHOICE; COMPLETED SUICIDE; DECISION-MAKING; WORKING-MEMORY; RATING-SCALE; IMPULSIVITY; DEPRESSION; THINKING; ADDICTS AB Background: The decision to commit suicide may be impulsive, but lethal suicidal acts often involve planning and forethought. People who attempt suicide make disadvantageous decisions in other contexts, but nothing is known about the way they decide about the future. Can the willingness to postpone future gratification differentiate between individuals prone to serious, premeditated and less serious, unplanned suicidal acts? Methods: Four groups of depressed participants aged 60 and older made choices between smaller immediate and larger delayed monetary rewards: 15 who had made high-lethality suicide attempts, 14 who had made low-lethality suicide attempts, 12 who seriously contemplated suicide, and 42 people with depression, but no history of suicidal thoughts. The reference group was 31 psychiatrically healthy elders. Results: Individuals who had made low-lethality attempts displayed an exaggerated preference for immediate rewards compared with nonsuicidal depressed and healthy control subjects. Those who had carried out high-lethality suicide attempts were more willing to delay future rewards, compared with low-lethality attempters. Better planned suicide attempts were also associated with willingness to wait for larger rewards. These effects were unchanged after accounting for education, global cognitive function, substance use disorders, psychotropic medications, and possible brain injury from attempts. Discount rates were correlated with having debt, but were not significantly associated with income, hopelessness, depressive severity, premorbid IQ, age at first attempt, or choice of violent means. Conclusions: Although clinicians often focus on impulsivity in patients at risk for suicide, these data suggest that identifying biological characteristics and treatments for nonimpulsive suicidal older people may be even more important. C1 [Dombrovski, Alexandre Y.; Szanto, Katalin; Siegle, Greg J.; Wallace, Meredith L.; Forman, Steven D.; Reynolds, Charles F., III] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. [Forman, Steven D.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sahakian, Barbara; Clark, Luke] Univ Cambridge, Dept Expt Psychol, Behav & Clin Neurosci Inst, Cambridge CB2 1TN, England. RP Dombrovski, AY (reprint author), Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. EM dombrovskia@upmc.edu RI Szanto, Katalin/B-8389-2014 OI Dombrovski, Alexandre/0000-0002-2054-4772 FU National Institute of Mental Health [K23 MH086620, K23 MH070471, P30MH52247, T32 MH016804]; Center for Injury Research and Control/Centers for Disease Control; American Foundation for Suicide Prevention; John A. Hartford Foundation; University of Pittsburgh Medical Center Endowment in Geriatric Psychiatry; Forest Laboratories; Pfizer; Bristol-Myers Squibb; Wyeth; Eli Lilly FX This work was supported by National Institute of Mental Health Grant Nos. K23 MH086620, K23 MH070471, P30MH52247, and T32 MH016804; Center for Injury Research and Control/Centers for Disease Control; the American Foundation for Suicide Prevention; the John A. Hartford Foundation, and the University of Pittsburgh Medical Center Endowment in Geriatric Psychiatry.; Dr. Sahakian has served as a consultant to Boehringer-Ingelheim, Cambridge Cognition, GlaxoSmithKline, Eli Lilly, Novartis, and Shire. Dr. Reynolds has received pharmaceutical supplies for his National Institutes of Health-sponsored work from Forest Laboratories, Pfizer, Bristol-Myers Squibb, Wyeth, and Eli Lilly. Dr. Clark has served as a consultant to Cambridge Cognition. Dr. Forman was employed as a Staff Physician, Behavioral Health Service, department of Veterans Affairs Medical Center, Pittsburgh, Pennsylvania, during the conduct of this study. The study contents do not represent the views of the Department of Veteran Affairs or the U. S. government. All other authors have no biomedical financial interests or potential conflicts of interest. NR 50 TC 53 Z9 53 U1 2 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 15 PY 2011 VL 70 IS 2 BP 138 EP 144 DI 10.1016/j.biopsych.2010.12.025 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 782UC UT WOS:000292036600008 PM 21329911 ER PT J AU Lange, S Gogel, S Leung, KY Vernay, B Nicholas, AP Causey, CP Thompson, PR Greene, NDE Ferretti, P AF Lange, Sigrun Goegel, Stefanie Leung, Kit-Yi Vernay, Bertrand Nicholas, Anthony P. Causey, Corey P. Thompson, Paul R. Greene, Nicholas D. E. Ferretti, Patrizia TI Protein deiminases: New players in the developmentally regulated loss of neural regenerative ability SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Apoptosis; Deimination/citrullination; Development; Peptidyl arginine deiminase; Regeneration; Spinal cord ID SPINAL-CORD-INJURY; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PEPTIDYLARGININE DEIMINASE; CITRULLINATED PROTEINS; ARGININE METHYLATION; MULTIPLE-SCLEROSIS; GENETIC INFLUENCES; FUNCTIONAL REPAIR; MOUSE-BRAIN; CELL-DEATH AB Spinal cord regenerative ability is lost with development, but the mechanisms underlying this loss are still poorly understood. In chick embryos, effective regeneration does not occur after E13, when spinal cord injury induces extensive apoptotic response and tissue damage. As initial experiments showed that treatment with a calcium chelator after spinal cord injury reduced apoptosis and cavitation, we hypothesized that developmentally regulated mediators of calcium-dependent processes in secondary injury response may contribute to loss of regenerative ability. To this purpose we screened for such changes in chick spinal cords at stages of development permissive (E11) and non-permissive (E15) for regeneration. Among the developmentally regulated calcium-dependent proteins identified was PAD3, a member of the peptidylarginine deiminase (PAD) enzyme family that converts protein arginine residues to citrulline, a process known as deimination or citrullination. This post-translational modification has not been previously associated with response to injury. Following injury, PAD3 up-regulation was greater in spinal cords injured at E15 than at E11. Consistent with these differences in gene expression, deimination was more extensive at the non-regenerating stage, E15, both in the gray and white matter. As deimination paralleled the extent of apoptosis, we investigated the effect of blocking PAD activity on cell death and deiminated-histone 3, one of the PAD targets we identified by mass-spectrometry analysis of spinal cord deiminated proteins. Treatment with the PAD inhibitor, Cl-amidine, reduced the abundance of deiminated-histone 3, consistent with inhibition of PAD activity, and significantly reduced apoptosis and tissue loss following injury at E15. Altogether, our findings identify PADs and deimination as developmentally regulated modulators of secondary injury response, and suggest that PADs might be valuable therapeutic targets for spinal cord injury. (C) 2011 Elsevier Inc. All rights reserved. C1 [Lange, Sigrun; Goegel, Stefanie; Vernay, Bertrand; Ferretti, Patrizia] UCL Inst Child Hlth, Dev Biol Unit, London WC1N 1EH, England. [Leung, Kit-Yi; Greene, Nicholas D. E.] UCL Inst Child Hlth, Neural Dev Unit, London WC1N 1EH, England. [Nicholas, Anthony P.] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. [Nicholas, Anthony P.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Causey, Corey P.] Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA. [Thompson, Paul R.] Scripps Res Inst, Dept Chem, Scripps Florida, FL 33458 USA. RP Ferretti, P (reprint author), UCL Inst Child Hlth, Dev Biol Unit, 30 Guilford St, London WC1N 1EH, England. EM ferretti@ich.ucl.ac.uk OI Ferretti, Patrizia/0000-0002-3590-6772; Vernay, Bertrand/0000-0002-7843-3872; Greene, Nicholas/0000-0002-4170-5248 FU BBSRC FX This work was supported by the BBSRC. NR 55 TC 33 Z9 34 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2011 VL 355 IS 2 BP 205 EP 214 DI 10.1016/j.ydbio.2011.04.015 PG 10 WC Developmental Biology SC Developmental Biology GA 787EN UT WOS:000292359500004 PM 21539830 ER PT J AU Gandy, S AF Gandy, Sam TI PERSPECTIVE Prevention is better than cure SO NATURE LA English DT Editorial Material ID ALZHEIMERS-DISEASE; COMPOUND-B C1 [Gandy, Sam] Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Gandy, Sam] James J Peters VA Med Ctr, New York, NY USA. RP Gandy, S (reprint author), Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY 10029 USA. EM samuel.gandy@mssm.edu FU NIA NIH HHS [P50 AG005138] NR 7 TC 15 Z9 16 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 14 PY 2011 VL 475 IS 7355 BP S15 EP S15 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 791UA UT WOS:000292690500007 PM 21760576 ER PT J AU Linefsky, JP O'Brien, KD Katz, R de Boer, IH Barasch, E Jenny, NS Siscovick, DS Kestenbaum, B AF Linefsky, Jason P. O'Brien, Kevin D. Katz, Ronit de Boer, Ian H. Barasch, Eddy Jenny, Nancy S. Siscovick, David S. Kestenbaum, Bryan TI Association of Serum Phosphate Levels With Aortic Valve Sclerosis and Annular Calcification The Cardiovascular Health Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE aortic valve; calcification; epidemiology; mitral valve; phosphate ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; VITAMIN-D LEVELS; PARATHYROID-HORMONE; VALVULAR CALCIFICATION; KIDNEY-FUNCTION; RENAL-FUNCTION; FETUIN-A; STENOSIS; ATHEROSCLEROSIS AB Objectives This study was conducted to evaluate mineral metabolism markers as potential risk factors for calcific aortic valve disease. Background Mineral metabolism disturbances are common among older people and may contribute to cardiac valvular calcification. Associations of serum mineral metabolism markers with cardiac valvular calcification have not been evaluated in a well-characterized general population of older adults. Methods We measured serum levels of phosphate, calcium, parathyroid hormone, and 25-hydroxyvitamin D in 1,938 Cardiovascular Health Study participants who were free of clinical cardiovascular disease and who underwent echo-cardiographic measurements of aortic valve sclerosis (AVS), mitral annular calcification (MAC), and aortic annular calcification (AAC). We used logistic regression models to estimate associations of mineral metabolism markers with AVS, MAC, and AAC after adjustment for relevant confounding variables, including kidney function. Results The respective prevalences of AVS, MAC, and AAC were 54%, 39%, and 44%. Each 0.5 mg/dl higher serum phosphate concentration was associated with greater adjusted odds of AVS (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.04 to 1.31, p = 0.01), MAC (OR: 1.12, 95% CI: 1.00 to 1.26, p = 0.05), and AAC (OR: 1.12, 95% CI: 0.99 to 1.25, p = 0.05). In contrast, serum calcium, parathyroid hormone, and 25-hydroxyvitamin D concentrations were not associated with aortic or mitral calcification. Conclusions Higher serum phosphate levels within the normal range were associated with valvular and annular calcification in a community-based cohort of older adults. Phosphate may be a novel risk factor for calcific aortic valve disease and warrants further study. (J Am Coll Cardiol 2011;58:291-7) (C) 2011 by the American College of Cardiology Foundation C1 [Linefsky, Jason P.; O'Brien, Kevin D.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Linefsky, Jason P.] Vet Affairs Puget Sound Hlth Care Syst, NW Ctr Excellence, Hlth Serv Res & Dev, Seattle, WA USA. [Katz, Ronit] Univ Washington, Dept Biostat, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [de Boer, Ian H.; Kestenbaum, Bryan] Univ Washington, Kidney Res Inst, Div Nephrol, Harborview Med Ctr, Seattle, WA 98195 USA. [Barasch, Eddy] St Francis Hosp, Dept Res & Educ, Roslyn, NY USA. [Jenny, Nancy S.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Siscovick, David S.] Univ Washington, Dept Med & Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. RP Linefsky, JP (reprint author), Univ Washington, Div Cardiol, 1959 NE Pacific St,Box 356422, Seattle, WA 98195 USA. EM linefsky@u.washington.edu FU National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295]; Department of Veterans Affairs Health Services Research and Development Service [TPM 61-034]; National Institutes of Health [R01 HL084443, R01 AG 027002] FX 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. The research reported in this article was supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, and N01-HC-45133, and grant number U01 HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additionally, the research reported here was supported by the Department of Veterans Affairs Health Services Research and Development Service, TPM 61-034. Funding for this study was also provided by National Institutes of Health R01 HL084443 and R01 AG 027002. Dr. O'Brien has received honoraria from Astra-Zeneca and Merck. The other authors have reported that they have no relationships to disclose. Dr. Linefsky is presently the post doc fellow at the Veterans Affairs Health Services Research and Development Northwest Center for Excellence. NR 47 TC 45 Z9 50 U1 0 U2 15 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 JUL 12 PY 2011 VL 58 IS 3 BP 291 EP 297 DI 10.1016/j.jacc.2010.11.073 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 788OB UT WOS:000292453200013 PM 21737022 ER PT J AU Bradley, SM Bryson, CL Maynard, C Maddox, TM Fihn, SD AF Bradley, Steven M. Bryson, Chris L. Maynard, Charles Maddox, Thomas M. Fihn, Stephan D. TI Recent hospitalization for Non-coronary events and use of preventive medications for coronary artery disease: An observational cohort study SO BMC CARDIOVASCULAR DISORDERS LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; LONG-TERM ADHERENCE; INFLUENZA VACCINATION RATES; OF-VETERANS-AFFAIRS; SECONDARY PREVENTION; FOLLOW-UP; CARE; QUALITY; RISK; GUIDELINES AB Background: High-quality systems have adopted a comprehensive approach to preventive care instead of diagnosis or procedure driven care. The current emphasis on prescribing medications to prevent complications of coronary artery disease (CAD) at discharge following an acute coronary syndrome (ACS) may exclude high-risk patients who are hospitalized with conditions other than ACS. Methods: Among a sample of patients with CAD treated at Veterans Affairs medical centers between January, 2005 and November, 2006, we investigated whether recent non-ACS hospitalization was associated with prescriptions of preventive medications as compared with patients recently hospitalized with ACS. Results: Of 13,211 patients with CAD, 58% received aspirin, 70% beta-blocker, 60% angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB), and 65% lipid-lowering therapy. Twenty-five percent of eligible patients were receiving all four medications. Having been hospitalized for a non-ACS event in the prior 6 months did not substantially affect the adjusted proportion on preventive medications. In contrast, among patients hospitalized for ACS in the prior 6 months, the adjusted proportion prescribed aspirin was 21% higher (p < 0.001), beta-blocker was 14% higher (p < 0.001), ACE-I or ARB was 9% higher (p < 0.001), lipid therapy was 12% higher (p < 0.001), and prescribed all four medications was 18% higher (p < 0.001) than among patients hospitalized for ACS more than 2 years earlier. Conclusions: Being hospitalized for a non-ACS condition did not appear to influence preventive medication use among patients with CAD and represents a missed opportunity to improve patient care. The same protocols employed to improve use of preventive medications in patients discharged for ACS might be extended to CAD patients discharged for other conditions as well. C1 [Bradley, Steven M.; Bryson, Chris L.; Maynard, Charles; Fihn, Stephan D.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev NW Ctr Excellence, Seattle, WA USA. [Bradley, Steven M.; Bryson, Chris L.; Maynard, Charles; Fihn, Stephan D.] Univ Washington, Seattle, WA 98195 USA. [Maddox, Thomas M.] Univ Colorado, Denver, CO 80202 USA. [Maddox, Thomas M.] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. RP Bradley, SM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev NW Ctr Excellence, Seattle, WA USA. EM Steve.Bradley@va.gov RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU Health Services Research and Development (HSRD); HSR&D's Quality Enhancement Research Initiative, Department of Veterans Affairs [IHD 98-001, MRC 03-334] FX This material is based upon work supported by Health Services Research and Development (HSR&D) and HSR&D's Quality Enhancement Research Initiative, Department of Veterans Affairs (Project#: IHD 98-001 and MRC 03-334). 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 32 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2261 J9 BMC CARDIOVASC DISOR JI BMC Cardiovasc. Disord. PD JUL 9 PY 2011 VL 11 AR 42 DI 10.1186/1471-2261-11-42 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 799FX UT WOS:000293271900001 PM 21740591 ER PT J AU Ting, TC Miyazaki-Anzai, S Masuda, M Levi, M Demer, LL Tintut, Y Miyazaki, M AF Ting, Tabitha C. Miyazaki-Anzai, Shinobu Masuda, Masashi Levi, Moshe Demer, Linda L. Tintut, Yin Miyazaki, Makoto TI Increased Lipogenesis and Stearate Accelerate Vascular Calcification in Calcifying Vascular Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC KIDNEY-DISEASE; DESATURASE-1 DEFICIENCY PROTECTS; DENSITY-LIPOPROTEIN CHOLESTEROL; ENDOPLASMIC-RETICULUM STRESS; POLYUNSATURATED FATTY-ACIDS; TOLL-LIKE RECEPTOR-4; X-RECEPTOR; BETA-CELLS; GENE-EXPRESSION; INDUCED LIPOTOXICITY AB Vascular calcification is recognized as an independent predictor of cardiovascular mortality, particularly in subjects with chronic kidney disease. However, the pathways by which dysregulation of lipid and mineral metabolism simultaneously occur in this particular population remain unclear. We have shown that activation of the farnesoid X receptor (FXR) blocks mineralization of bovine calcifying vascular cells (CVCs) and in ApoE knock-out mice with 5/6 nephrectomy. In contrast to FXR, this study showed that liver X receptor (LXR) activation by LXR agonists and adenovirus-mediated LXR overexpression by VP16-LXR alpha and VP16-LXR beta accelerated mineralization of CVCs. Conversely, LXR inhibition by dominant negative (DN) forms of LXR alpha and LXR beta reduced calcium content in CVCs. The regulation of mineralization by FXR and LXR agonists was highly correlated with changes in lipid accumulation, fatty acid synthesis, and the expression of sterol regulatory element binding protein-1 (SREBP-1). The rate of lipogenesis in CVCs through the SREBP-1c dependent pathway was reduced by FXR activation, but increased by LXR activation. SREBP-1c overexpression augmented mineralization in CVCs, whereas SREBP-1c DN inhibited alkaline phosphatase activity and mineralization induced by LXR agonists. LXR and SREBP-1c activations increased, whereas FXR activation decreased, saturated and monounsaturated fatty acids derived from lipogenesis. In addition, we found that stearate markedly promoted mineralization of CVCs as compared with other fatty acids. Furthermore, inhibition of either acetyl-CoA carboxylase or acyl-CoA synthetase reduced mineralization of CVCs, whereas inhibition of stearoyl-CoA desaturase induced mineralization. Therefore, a stearate metabolite derived from lipogenesis might be a risk factor for the development of vascular calcification. C1 [Miyazaki, Makoto] Univ Colorado Denver, Dept Med, Div Renal Dis & Hypertens, Aurora, CO 80045 USA. [Ting, Tabitha C.; Miyazaki-Anzai, Shinobu; Masuda, Masashi; Levi, Moshe; Miyazaki, Makoto] Denver VA Med Ctr, Div Renal Dis & Hypertens, Dept Med, Aurora, CO 80045 USA. [Miyazaki, Makoto] Denver VA Med Ctr, Div Endocrinol Diabet & Metab, Dept Med, Aurora, CO 80045 USA. [Demer, Linda L.; Tintut, Yin] Univ Calif Los Angeles, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA. RP Miyazaki, M (reprint author), Univ Colorado Denver, Dept Med, Div Renal Dis & Hypertens, 12700 E 19th Ave,C281, Aurora, CO 80045 USA. EM Makoto.Miyazaki@ucdenver.edu RI Demer, Linda/I-5770-2013 OI Demer, Linda/0000-0002-9618-6895; Levi, Moshe/0000-0002-6225-946X FU National Institutes of Health [HL081202, DK081346]; American Heart Association [10BGIA458005]; Colorado Clinical Nutrition Research Unit (National Institutes of Health) [5P30DK048520]; UCHSC Diabetes and Endocrinology Research Center (National Institutes of Health) [P30DK57516]; NIGMS-IMSD [R25GM083333] FX This work was supported, in whole or in part, by National Institutes of Health Grants HL081202 and DK081346, the American Heart Association Grant 10BGIA458005, as well as the Colorado Clinical Nutrition Research Unit (National Institutes of Health Grant 5P30DK048520), and the UCHSC Diabetes and Endocrinology Research Center (National Institutes of Health Grant P30DK57516). T. C. T. was supported by NIGMS-IMSD #R25GM083333. NR 48 TC 13 Z9 14 U1 0 U2 10 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 JUL 8 PY 2011 VL 286 IS 27 BP 23938 EP 23949 DI 10.1074/jbc.M111.237065 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 786HO UT WOS:000292294900036 PM 21596756 ER PT J AU Pereira, RI Wang, CCL Hosokawa, P Dickinson, LM Chonchol, M Krantz, MJ Steiner, JF Bessesen, DH Havranek, EP Long, CS AF Pereira, Rocio I. Wang, Cecilia C. L. Hosokawa, Patrick Dickinson, L. Miriam Chonchol, Michel Krantz, Mori J. Steiner, John F. Bessesen, Daniel H. Havranek, Edward P. Long, Carlin S. TI Circulating adiponectin levels are lower in Latino versus non-Latino white patients at risk for cardiovascular disease, independent of adiposity measures SO BMC ENDOCRINE DISORDERS LA English DT Article ID BODY-FAT DISTRIBUTION; TYPE-2 DIABETIC-PATIENTS; INSULIN SENSITIVITY; MEXICAN-AMERICANS; ESSENTIAL-HYPERTENSION; AFRICAN-AMERICANS; PROTEIN ACRP30; PLASMA; OBESITY; RESISTANCE AB Background: Latinos in the United States have a higher prevalence of type 2 diabetes than non-Latino whites, even after controlling for adiposity. Decreased adiponectin is associated with insulin resistance and predicts T2DM, and therefore may mediate this ethnic difference. We compared total and high-molecular-weight (HMW) adiponectin in Latino versus white individuals, identified factors associated with adiponectin in each ethnic group, and measured the contribution of adiponectin to ethnic differences in insulin resistance. Methods: We utilized cross-sectional data from subjects in the Latinos Using Cardio Health Actions to reduce Risk study. Participants were Latino (n = 119) and non-Latino white (n = 60) men and women with hypertension and at least one other risk factor for CVD (age 61 +/- 10 yrs, 49% with T2DM), seen at an integrated community health and hospital system in Denver, Colorado. Total and HMW adiponectin was measured by RIA and ELISA respectively. Fasting glucose and insulin were used to calculate the homeostasis model insulin resistance index (HOMA-IR). Variables independently associated with adiponectin levels were identified by linear regression analyses. Adiponectin's contribution to ethnic differences in insulin resistance was assessed in multivariate linear regression models of Latino ethnicity, with logHOMA-IR as a dependent variable, adjusting for possible confounders including age, gender, adiposity, and renal function. Results: Mean adiponectin levels were lower in Latino than white patients (beta estimates: -4.5 (-6.4, -2.5), p < 0.001 and -1.6 (-2.7, -0.5), p < 0.005 for total and HMW adiponectin), independent of age, gender, BMI/waist circumference, thiazolidinedione use, diabetes status, and renal function. An expected negative association between adiponectin and waist circumference was seen among women and non- Latino white men, but no relationship between these two variables was observed among Latino men. Ethnic differences in logHOMA- IR were no longer observed after controlling for adiponectin levels. Conclusions: Among patients with CVD risk, total and HMW adiponectin is lower in Latinos, independent of adiposity and other known regulators of adiponectin. Ethnic differences in adiponectin regulation may exist and future research in this area is warranted. Adiponectin levels accounted for the observed variability in insulin resistance, suggesting a contribution of decreased adiponectin to insulin resistance in Latino populations. C1 [Pereira, Rocio I.; Krantz, Mori J.; Bessesen, Daniel H.; Havranek, Edward P.; Long, Carlin S.] Denver Hlth Med Ctr, Denver, CO 80204 USA. [Pereira, Rocio I.; Wang, Cecilia C. L.; Hosokawa, Patrick; Dickinson, L. Miriam; Chonchol, Michel; Bessesen, Daniel H.] Univ Colorado Denver, Aurora, CO 80045 USA. [Wang, Cecilia C. L.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. [Steiner, John F.] Kaiser Permanente, Inst Hlth Res, Denver, CO 80237 USA. RP Pereira, RI (reprint author), Denver Hlth Med Ctr, 660 Bannock St, Denver, CO 80204 USA. EM rocio.pereira@ucdenver.edu FU National Heart Lung and Blood Institute (NHLBI), component of the National Institutes of Health (NIH) [U01 HL079160, U01 HL079208]; National Center for Research Resources, component of the National Institutes of Health (NIH) [K23 RR0222238] FX The project described was supported by Grant Numbers U01 HL079160 and U01 HL079208 from the National Heart Lung and Blood Institute (NHLBI) and Grant Number K23 RR0222238 from the National Center for Research Resources, both components of the National Institutes of Health (NIH). The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of NCRR, NHLBI, or NIH. NR 36 TC 7 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6823 J9 BMC ENDOCR DISORD JI BMC Endocr. Disord. PD JUL 7 PY 2011 VL 11 AR 13 DI 10.1186/1472-6823-11-13 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 851SI UT WOS:000297290800001 PM 21736747 ER PT J AU O'Connor, CM Starling, RC Hernandez, AF Armstrong, PW Dickstein, K Hasselblad, V Heizer, GM Komajda, M Massie, BM McMurray, JJV Nieminen, MS Reist, CJ Rouleau, JL Swedberg, K Adams, KF Anker, SD Atar, D Battler, A Botero, R Bohidar, NR Butler, J Clausell, N Corbalan, R Costanzo, MR Dahlstrom, U Deckelbaum, LI Diaz, R Dunlap, ME Ezekowitz, JA Feldman, D Felker, GM Fonarow, GC Gennevois, D Gottlieb, SS Hill, JA Hollander, JE Howlett, JG Hudson, MP Kociol, RD Krum, H Laucevicius, A Levy, WC Mendez, GF Metra, M Mittal, S Oh, BH Pereira, NL Ponikowski, P Wilson, WH Tanomsup, S Teerlink, JR Triposkiadis, F Troughton, RW Voors, AA Whellan, DJ Zannad, F Califf, RM AF O'Connor, C. M. Starling, R. C. Hernandez, A. F. Armstrong, P. W. Dickstein, K. Hasselblad, V. Heizer, G. M. Komajda, M. Massie, B. M. McMurray, J. J. V. Nieminen, M. S. Reist, C. J. Rouleau, J. L. Swedberg, K. Adams, K. F., Jr. Anker, S. D. Atar, D. Battler, A. Botero, R. Bohidar, N. R. Butler, J. Clausell, N. Corbalan, R. Costanzo, M. R. Dahlstrom, U. Deckelbaum, L. I. Diaz, R. Dunlap, M. E. Ezekowitz, J. A. Feldman, D. Felker, G. M. Fonarow, G. C. Gennevois, D. Gottlieb, S. S. Hill, J. A. Hollander, J. E. Howlett, J. G. Hudson, M. P. Kociol, R. D. Krum, H. Laucevicius, A. Levy, W. C. Mendez, G. F. Metra, M. Mittal, S. Oh, B. -H. Pereira, N. L. Ponikowski, P. Wilson, W. H. Tanomsup, S. Teerlink, J. R. Triposkiadis, F. Troughton, R. W. Voors, A. A. Whellan, D. J. Zannad, F. Califf, R. M. TI Effect of Nesiritide in Patients with Acute Decompensated Heart Failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; NATIONAL REGISTRY ADHERE; HOSPITALIZED-PATIENTS; OUTCOMES; POPULATION; DIURETICS; RISK AB Background Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. Methods We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. Results Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P = 0.03) and 24 hours (68.2% vs. 66.1%, P = 0.007), but the prespecified level for significance (P = 0.005 for both assessments or Pd <= 0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P = 0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P = 0.11). Conclusions Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. C1 [O'Connor, C. M.; Hernandez, A. F.; Hasselblad, V.; Heizer, G. M.; Reist, C. J.; Felker, G. M.; Kociol, R. D.; Califf, R. M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA. [Adams, K. F., Jr.] Univ N Carolina, Heart Failure Program, Chapel Hill, NC USA. [Starling, R. C.; Wilson, W. H.] Cleveland Clin, Cleveland, OH USA. [Dunlap, M. E.] MetroHlth Med Ctr, Heart & Vasc Ctr, Cleveland, OH USA. [Rouleau, J. L.] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Armstrong, P. W.; Ezekowitz, J. A.] Univ Alberta, Edmonton, AB, Canada. [Howlett, J. G.] Dalhousie Univ, Halifax, NS, Canada. [Dickstein, K.] Univ Bergen, Stavenger Univ Hosp, Bergen, Norway. [Komajda, M.] Univ Paris 06, Paris, France. [Komajda, M.] Hop La Pitie Salpetriere, Paris, France. [Massie, B. M.; Teerlink, J. R.] Univ Calif San Francisco, San Francisco Vet Affairs VA Hosp, San Francisco, CA 94143 USA. [Massie, B. M.; Teerlink, J. R.] San Francisco VA Med Ctr, San Francisco, CA USA. [McMurray, J. J. V.] Univ Glasgow, Western Infirm, Glasgow G11 6NT, Lanark, Scotland. [Nieminen, M. S.] Meilahti Hosp, Helsinki, Finland. [Swedberg, K.] Univ Gothenburg, Dept Emergency & Cardiovasc Med, Gothenburg, Sweden. [Dahlstrom, U.] Linkoping Univ, Div Cardiovasc Med, Dept Med & Hlth Sci, Linkoping, Sweden. [Anker, S. D.] IRCCS, Ctr Clin & Basic Res, Rome, Italy. [Anker, S. D.] Charite, Dept Cardiol, D-13353 Berlin, Germany. [Atar, D.] Aker Univ Hosp, Oslo, Norway. [Battler, A.] Rabin Med Ctr, Dept Cardiol, Petah Tiqwa, Israel. [Botero, R.] Clin Medellin, Medellin, Colombia. [Bohidar, N. R.; Deckelbaum, L. I.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Butler, J.] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. [Clausell, N.] Hosp Clin Porto Alegre, Serv Cardiol, Porto Alegre, RS, Brazil. [Corbalan, R.] Pontificia Univ Catolica Chile, Div Cardiovasc, Santiago, Chile. [Costanzo, M. R.] Edward Heart Hosp, Naperville, IL USA. [Diaz, R.] Estudios Cardiol Latino Amer, Rosario, Santa Fe, Argentina. [Fonarow, G. C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Feldman, D.] Minneapolis Heart Inst, Minneapolis, MN USA. [Gennevois, D.] Janssen Alzheimer Immunotherapy, San Francisco, CA USA. [Gottlieb, S. S.] Univ Maryland Hosp, Div Cardiol, Baltimore, MD 21201 USA. [Hill, J. A.] Univ Florida, Gainesville, FL USA. [Hollander, J. E.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Whellan, D. J.] Thomas Jefferson Univ, Jefferson Med Coll, Div Cardiol, Philadelphia, PA 19107 USA. [Hudson, M. P.] Edith & Benson Ford Heart & Vasc Inst, Detroit, MI USA. [Krum, H.] Monash Univ, Prahran, Vic, Australia. [Krum, H.] Alfred Hosp, Dept Epidemiol & Prevent Med, Prahran, Vic, Australia. [Laucevicius, A.] Vilnius Univ Hosp, Santariskiu Klin, Dept Cardiol & Angiol, Vilnius, Lithuania. [Levy, W. C.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Mendez, G. F.] Alta Especialidad Hosp Especialidades, Inst Mexicano Seguro Social 14, Unidades Med, Cordoba, Veracruz, Mexico. [Metra, M.] Univ Brescia, Dept Cardiol, Brescia, Italy. [Mittal, S.] Escorts Heart Inst & Res Ctr, Dept Cardiol, New Delhi, India. [Oh, B. -H.] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul Natl Univ Hosp, Seoul 151, South Korea. [Pereira, N. L.] Mayo Clin, Rochester, MN USA. [Ponikowski, P.] Med Univ, Dept Heart Dis, Wroclaw, Poland. [Tanomsup, S.] Mahidol Univ, Ramathibodi Hosp, Fac Med, Div Cardiol, Bangkok 10400, Thailand. [Triposkiadis, F.] Univ Hosp Larissa, Dept Cardiol, Larisa, Greece. [Troughton, R. W.] Univ Otago, Christchurch, New Zealand. [Voors, A. A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Zannad, F.] Ctr Hosp Univ, INSERM, Ctr Invest Clin 9501, Nancy, France. [Zannad, F.] Ctr Hosp Univ, Inst Lorrain Coeur & Vaisseaux, U961, Nancy, France. RP O'Connor, CM (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Box 3356, Durham, NC 27710 USA. EM oconn002@mc.duke.edu RI Teerlink, John/D-2986-2012; Ezekowitz, Justin/C-4579-2013; Oh, Byung-Hee/G-9875-2011; Clausell, Nadine /C-7813-2016; Ponikowski, Piotr/O-6454-2015; Hernandez, Adrian F./A-7818-2016 OI Ezekowitz, Justin/0000-0002-2724-4086; Clausell, Nadine /0000-0003-4207-3809; Ponikowski, Piotr/0000-0002-3391-7064; Hollander, Judd/0000-0002-1318-2785; Hernandez, Adrian F./0000-0003-3387-9616; Metra, Marco/0000-0001-6691-8568; mcmurray, john/0000-0002-6317-3975 FU Scios FX Funded by Scios NR 26 TC 453 Z9 472 U1 2 U2 25 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 JUL 7 PY 2011 VL 365 IS 1 BP 32 EP 43 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 788QL UT WOS:000292459400007 PM 21732835 ER PT J AU Khan, M Sakakima, H Dhammu, TS Shunmugavel, A Im, YB Gilg, AG Singh, AK Singh, I AF Khan, Mushfiquddin Sakakima, Harutoshi Dhammu, Tajinder S. Shunmugavel, Anandakumar Im, Yeong-Bin Gilg, Anne G. Singh, Avtar K. Singh, Inderjit TI S-Nitrosoglutathione reduces oxidative injury and promotes mechanisms of neurorepair following traumatic brain injury in rats SO JOURNAL OF NEUROINFLAMMATION LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; NITRIC-OXIDE SYNTHASE; SPINAL-CORD-INJURY; NF-KAPPA-B; RECEPTOR AGONIST 8-OH-DPAT; THERAPEUTIC TIME WINDOW; CORTICAL IMPACT INJURY; ENDOTHELIAL DYSFUNCTION; EXPERIMENTAL STROKE; PROTECTS BRAIN AB Background: Traumatic brain injury (TBI) induces primary and secondary damage in both the endothelium and the brain parenchyma, collectively termed the neurovascular unit. While neurons die quickly by necrosis, a vicious cycle of secondary injury in endothelial cells exacerbates the initial injury in the neurovascular unit following TBI. In activated endothelial cells, excessive superoxide reacts with nitric oxide (NO) to form peroxynitrite. Peroxynitrite has been implicated in blood brain barrier (BBB) leakage, altered metabolic function, and neurobehavioral impairment. S-nitrosoglutathione (GSNO), a nitrosylation-based signaling molecule, was reported not only to reduce brain levels of peroxynitrite and oxidative metabolites but also to improve neurological function in TBI, stroke, and spinal cord injury. Therefore, we investigated whether GSNO promotes the neurorepair process by reducing the levels of peroxynitrite and the degree of oxidative injury. Methods: TBI was induced by controlled cortical impact (CCI) in adult male rats. GSNO or 3-Morpholinosydnonimine (SIN-1) (50 mu g/kg body weight) was administered orally two hours following CCI. The same dose was repeated daily until endpoints. GSNO-treated (GSNO group) or SIN-1-treated (SIN-1 group) injured animals were compared with vehicle-treated injured animals (TBI group) and vehicle-treated sham-operated animals (Sham group) in terms of peroxynitrite, NO, glutathione (GSH), lipid peroxidation, blood brain barrier (BBB) leakage, edema, inflammation, tissue structure, axon/myelin integrity, and neurotrophic factors. Results: SIN-1 treatment of TBI increased whereas GSNO treatment decreased peroxynitrite, lipid peroxides/aldehydes, BBB leakage, inflammation and edema in a short-term treatment (4-48 hours). GSNO also reduced brain infarctions and enhanced the levels of NO and GSH. In a long-term treatment (14 days), GSNO protected axonal integrity, maintained myelin levels, promoted synaptic plasticity, and enhanced the expression of neurotrophic factors. Conclusion: Our findings indicate the participation of peroxynitrite in the pathobiology of TBI. GSNO treatment of TBI not only reduces peroxynitrite but also protects the integrity of the neurovascular unit, indicating that GSNO blunts the deleterious effects of peroxynitrite. A long-term treatment of TBI with the same low dose of GSNO promotes synaptic plasticity and enhances the expression of neurotrophic factors. These results support that GSNO reduces the levels of oxidative metabolites, protects the neurovascular unit, and promotes neurorepair mechanisms in TBI. C1 [Khan, Mushfiquddin; Sakakima, Harutoshi; Dhammu, Tajinder S.; Shunmugavel, Anandakumar; Im, Yeong-Bin; Gilg, Anne G.; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Singh, Avtar K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 171 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu FU National Institutes of Health [NS-72511, NS-22576, NS-37766]; Betty L. Beatty Foundation; Guy E. Beatty Foundation; Veteran Administration; NIH National Center for Research Resources [C06 RR018823, C06 RR015455] FX These studies were supported by grants from National Institutes of Health (NS-72511, NS-22576 and NS-37766), Betty L. Beatty and Guy E. Beatty Foundations, and Veteran Administration merit awards. This work was also supported by the NIH, Grants C06 RR018823 and No C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources. We are grateful to Dr Tom Smith and Dr Melissa A Crofton from the MUSC Writing Center for their valuable editing and correction of the manuscript. We would like to thank Ms Joyce Bryan for procurement of animals and chemicals, and Ms Chara Williams for secretarial assistance. NR 97 TC 31 Z9 35 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD JUL 6 PY 2011 VL 8 AR 78 DI 10.1186/1742-2094-8-78 PG 17 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 810UH UT WOS:000294152500001 PM 21733162 ER PT J AU Frei, CR Bell, AM Traugott, KA Jaso, TC Daniels, KR Mortensen, EM Restrepo, MI Oramasionwu, CU Ruiz, AD Mylchreest, WR Sikirica, V Raut, MR Fisher, A Schein, JR AF Frei, Christopher R. Bell, Allison M. Traugott, Kristi A. Jaso, Terry C. Daniels, Kelly R. Mortensen, Eric M. Restrepo, Marcos I. Oramasionwu, Christine U. Ruiz, Andres D. Mylchreest, William R. Sikirica, Vanja Raut, Monika R. Fisher, Alan Schein, Jeff R. TI A clinical pathway for community-acquired pneumonia: an observational cohort study SO BMC INFECTIOUS DISEASES LA English DT Article ID AZITHROMYCIN PLUS CEFTRIAXONE; STREPTOCOCCUS-PNEUMONIAE; HOSPITALIZED-PATIENTS; OPEN-LABEL; 500 MG; LEVOFLOXACIN; PHARMACODYNAMICS; MULTICENTER; CLARITHROMYCIN; GUIDELINES AB Background: Six hospitals instituted a voluntary, system-wide, pathway for community acquired pneumonia (CAP). We proposed this study to determine the impact of pathway antibiotics on patient survival, hospital length of stay (LOS), and total hospital cost. Methods: Data were collected for adults from six U. S. hospitals with a principal CAP discharge diagnosis code, a chest infiltrate, and medical notes indicative of CAP from 2005-2007. Pathway and non-pathway cohorts were assigned according to antibiotics received within 48 hours of admission. Pathway antibiotics included levofloxacin 750 mg monotherapy or ceftriaxone 1000 mg plus azithromycin 500 mg daily. Multivariable regression models assessed 90-day mortality, hospital LOS, total hospital cost, and total pharmacy cost. Results: Overall, 792 patients met study criteria. Of these, 505 (64%) received pathway antibiotics and 287 (36%) received non-pathway antibiotics. Adjusted means and p-values were derived from Least Squares regression models that included Pneumonia Severity Index risk class, patient age, heart failure, chronic obstructive pulmonary disease, and admitting hospital as covariates. After adjustment, patients who received pathway antibiotics experienced lower adjusted 90-day mortality (p = 0.02), shorter mean hospital LOS (3.9 vs. 5.0 days, p < 0.01), lower mean hospital costs ($2,485 vs. $3,281, p = 0.02), and similar mean pharmacy costs ($356 vs. $442, p = 0.11). Conclusions: Pathway antibiotics were associated with improved patient survival, hospital LOS, and total hospital cost for patients admitted to the hospital with CAP. C1 [Frei, Christopher R.; Bell, Allison M.; Traugott, Kristi A.; Jaso, Terry C.; Daniels, Kelly R.; Oramasionwu, Christine U.; Ruiz, Andres D.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Frei, Christopher R.; Bell, Allison M.; Traugott, Kristi A.; Daniels, Kelly R.; Oramasionwu, Christine U.; Ruiz, Andres D.] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. [Traugott, Kristi A.] ALMD UTHSCSA, S Texas Vet Healthcare Syst, Dept Pharm, San Antonio, TX 78229 USA. [Jaso, Terry C.; Mylchreest, William R.] Seton Family Hosp, Austin, TX 78720 USA. [Daniels, Kelly R.; Ruiz, Andres D.] Oakdell Pharm Inc, San Antonio, TX 78229 USA. [Mortensen, Eric M.; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Mortensen, Eric M.; Restrepo, Marcos I.] ALMD UTHSCSA, S Texas Vet Healthcare Syst, VERDICT, San Antonio, TX 78229 USA. [Sikirica, Vanja; Raut, Monika R.; Fisher, Alan; Schein, Jeff R.] Ortho McNeil Janssen Sci Affairs LLC, Raritan, NJ 08869 USA. RP Frei, CR (reprint author), Univ Texas Austin, Coll Pharm, 1 Univ Stn A1900, Austin, TX 78712 USA. EM freic@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 OI Mortensen, Eric/0000-0002-3880-5563 FU NIH; AstraZeneca; Elan; Ortho McNeil Janssen Pharmaceuticals; Pfizer FX CRF has received research grants and/or served as a scientific consultant/advisor for the NIH, AstraZeneca, Elan, Ortho McNeil Janssen Pharmaceuticals, and Pfizer. MIR is on the speaker's bureaus of Ortho-McNeil Janssen, Johnson & Johnson, Pfizer, and BARD, Inc. He has also served on Advisory Boards for Forest, Ortho-McNeil Janssen, Johnson & Johnson, Pfizer, and BARD, Inc. VS, MRR, AF, and JRS are current or former employees of Ortho McNeil Janssen Scientific Affairs, LLC. AMB, KAT, TCJ, KRD, EMM, CUO, ADR, and WRM have nothing to disclose related to the content of this manuscript. NR 26 TC 5 Z9 5 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD JUL 6 PY 2011 VL 11 AR 188 DI 10.1186/1471-2334-11-188 PG 6 WC Infectious Diseases SC Infectious Diseases GA 795WJ UT WOS:000293008500001 PM 21733161 ER PT J AU Taborsky, GJ AF Taborsky, Gerald J., Jr. TI Islets Have a Lot of Nerve! Or Do They? SO CELL METABOLISM LA English DT Editorial Material ID GLUCAGON-SECRETION; ENDOCRINE PANCREAS; ACTIVATION; HYPOGLYCEMIA; DOG C1 [Taborsky, Gerald J., Jr.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Taborsky, Gerald J., Jr.] Univ Washington, Seattle, WA 98108 USA. RP Taborsky, GJ (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. EM taborsky@u.washington.edu FU NIDDK NIH HHS [R01 DK050154] NR 10 TC 9 Z9 10 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 JUL 6 PY 2011 VL 14 IS 1 BP 5 EP 6 DI 10.1016/j.cmet.2011.06.004 PG 2 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 790JB UT WOS:000292583200003 PM 21723498 ER PT J AU Zile, MR Gaasch, WH AF Zile, Michael R. Gaasch, William H. TI Abnormal Calcium Homeostasis One Mechanism in Diastolic Heart Failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE calcium; diastole; heart failure; hypertrophy; tachycardia ID VENTRICULAR EJECTION FRACTION; DISEASE; INSIGHTS C1 [Zile, Michael R.] Med Univ S Carolina, Div Cardiol, Charleston, SC 29425 USA. [Zile, Michael R.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. [Gaasch, William H.] Lahey Clin Fdn, Dept Cardiovasc Med, Burlington, MA USA. RP Zile, MR (reprint author), Med Univ S Carolina, Div Cardiol, Ashley River Towers,Room 7067,25 Courtenay Dr, Charleston, SC 29425 USA. EM zilem@musc.edu NR 13 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 5 PY 2011 VL 58 IS 2 BP 155 EP 157 DI 10.1016/j.jacc.2010.10.068 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 784WN UT WOS:000292189300010 PM 21718912 ER PT J AU Aujesky, D Roy, PM Verschuren, F Righini, M Osterwalder, J Egloff, M Renaud, B Verhamme, P Stone, RA Legal, C Sanchez, O Pugh, NA N'gako, A Cornuz, J Hugii, O Beer, HJ Perrier, A Fine, MJ Yealy, DM AF Aujesky, Drahomir Roy, Pierre-Marie Verschuren, Franck Righini, Marc Osterwalder, Joseph Egloff, Michael Renaud, Bertrand Verhamme, Peter Stone, Roslyn A. Legal, Catherine Sanchez, Olivier Pugh, Nathan A. N'gako, Alfred Cornuz, Jacques Hugii, Olivier Beer, Hans-Juerg Perrier, Arnaud Fine, Michael J. Yealy, Donald M. TI Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial SO LANCET LA English DT Article ID MOLECULAR-WEIGHT HEPARIN; DEEP-VEIN THROMBOSIS; INTRAVENOUS UNFRACTIONATED HEPARIN; VENOUS THROMBOEMBOLIC DISEASE; CLINICAL PROGNOSTIC MODEL; LOW-RISK PATIENTS; EARLY DISCHARGE; ANTICOAGULANT-THERAPY; INITIAL TREATMENT; SEVERITY INDEX AB Background Although practice guidelines recommend outpatient care for selected, haemodynamically stable patients with pulmonary embolism, most treatment is presently inpatient based. We aimed to assess non-inferiority of outpatient care compared with inpatient care. Methods We undertook an open-label, randomised non-inferiority trial at 19 emergency departments in Switzerland, France, Belgium, and the USA. We randomly assigned patients with acute, symptomatic pulmonary embolism and a low risk of death (pulmonary embolism severity index risk classes I or II) with a computer-generated randomisation sequence (blocks of 2-4) in a 1:1 ratio to initial outpatient (ie, discharged from hospital <= 24 h after randomisation) or inpatient treatment with subcutaneous enoxaparin (>= 5 days) followed by oral anticoagulation (>= 90 days). The primary outcome was symptomatic, recurrent venous thromboembolism within 90 days; safety outcomes included major bleeding within 14 or 90 days and mortality within 90 days. We used a non-inferiority margin of 4% for a difference between inpatient and outpatient groups. We included all enrolled patients in the primary analysis, excluding those lost to follow-up. This trial is registered with ClinicalTrials.gov, number NCT00425542. Findings Between February, 2007, and June, 2010, we enrolled 344 eligible patients. In the primary analysis, one (0.6%) of 171 outpatients developed recurrent venous thromboembolism within 90 days compared with none of 168 inpatients (95% upper confidence limit [UCL] 2-7%; p=0.011). Only one (0.6%) patient in each treatment group died within 90 days (95% UCL 2.1%; p=0.005), and two (1.2%) of 171 outpatients and no inpatients had major bleeding within 14 days (95% UCL 3.6%; p=0.031). By 90 days, three (1.8%) outpatients but no inpatients had developed major bleeding (95% UCL 4.5%; p=0.086). Mean length of stay was 0.5 days (SD 1.0) for outpatients and 3.9 days (SD 3.1) for inpatients. Interpretation In selected low-risk patients with pulmonary embolism, outpatient care can safely and effectively be used in place of inpatient care. C1 [Aujesky, Drahomir] Univ Hosp Bern, Univ Klin Allgemeine Innere Med, Inselspital, CH-3010 Bern, Switzerland. [Roy, Pierre-Marie] LUNAM Univ, Angers, France. [Roy, Pierre-Marie] Univ Angers, Angers, France. [Verschuren, Franck] Univ Louvain, Brussels, Belgium. [Righini, Marc; Perrier, Arnaud] Univ Geneva, Geneva, Switzerland. [Osterwalder, Joseph] Cantonal Hosp St Gallen, St Gallen, Switzerland. [Egloff, Michael; Beer, Hans-Juerg] Cantonal Hosp Baden, Baden, Switzerland. [Renaud, Bertrand; N'gako, Alfred] Univ Hosp Henri Mondor, Creteil, France. [Verhamme, Peter] Univ Louvain, Louvain, Belgium. [Fine, Michael J.] Univ Pittsburgh, VA Ctr Hlth Equity Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Fine, Michael J.] Univ Pittsburgh, Div Gen Internal Med, Sch Med, Pittsburgh, PA 15260 USA. [Stone, Roslyn A.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15260 USA. [Yealy, Donald M.] Univ Pittsburgh, Dept Emergency Med, Pittsburgh, PA 15260 USA. [Legal, Catherine] Univ Argenteuil, Argenteuil, France. [Sanchez, Olivier] Hop Europeen Georges Pompidou, Paris, France. [Cornuz, Jacques; Hugii, Olivier] Univ Lausanne, Lausanne, Switzerland. RP Aujesky, D (reprint author), Univ Hosp Bern, Univ Klin Allgemeine Innere Med, Inselspital, CH-3010 Bern, Switzerland. EM drahomir.aujesky@insel.ch RI Perrier, Arnaud/M-2263-2014 OI Hugli, Olivier/0000-0003-2312-1625 FU Swiss National Science Foundation [3200B0-1121]; Programme Hospitalier de Recherche Clinique [21-03]; US National Heart, Lung, and Blood Institute [1R01HL085565-01A2]; GlaxoSmithKline; Sanofi-Aventis; Bayer; Biomerieux; Boehringer Ingelheim; Eli Lilly; LFB Biomedicaments; Daiichi-Sankyo; ThromboGenics; Leo; Pfizer; MSD; Menarini FX Swiss National Science Foundation, Programme Hospitalier de Recherche Clinique, and the US National Heart, Lung, and Blood Institute. Sanofi-Aventis provided free drug supply in the participating European centres.; DA has received honoraria from Sanofi-Aventis and Bayer. PM R has received grants, honoraria, consultancy fees, and payments from GlaxoSmithKline, Sanofi-Aventis, Bayer, Biomerieux, Boehringer Ingelheim, Eli Lilly, and LFB Biomedicaments. PV has received grants, consultancy fees, and payments from Sanofi-Aventis, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, ThromboGenics, Leo, and Pfizer. OH has received grants from Pfizer and MSD. HJB has received honoraria from Sariofi-Aventis, Bayer, Boehringer Ingelheim, Menarini, and GlaxoSmithKline.; This study was supported by grants from the Swiss National Science Foundation (3200B0-1121), the Programme Hospitalier de Recherche Clinique 2007 (21-03), and the US National Heart, Lung, and Blood Institute (1R01HL085565-01A2). Sanofi-Aventis provided free drug supply in the participating European centres. We thank Emmanuelle Le Moigne (Brest, France), David Elkharrat (Boulogne, France), Dominique Elkouri (Nantes, France), Mark Courtney (Chicago, IL, USA), Didier Honnart (Dijon, France), Jeannot Schmidt (Clermont-Ferrand, France), Jeffrey Kline (Charlotte, NC, USA), Yves Poitrineau (Thiers, France), and Bertrand Yersin (Lausanne, Switzerland). NR 43 TC 190 Z9 192 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JUL 2 PY 2011 VL 378 IS 9785 BP 41 EP 48 DI 10.1016/S0140-6736(11)60824-6 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 791IU UT WOS:000292659700032 PM 21703676 ER PT J AU Buxbaum, LU DeRitis, PC Chu, NS Conti, PA AF Buxbaum, Laurence U. DeRitis, Pierina C. Chu, Niansheng Conti, Pierre A. TI Eliminating Murine Norovirus by Cross-Fostering SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID MICE; INFECTION; VIRUS; ERADICATION; PREVALENCE; IMMUNITY AB Murine norovirus (MNV) is a newly discovered and extremely prevalent pathogen of laboratory mouse colonies. MNV causes severe disease in some immunocompromised mouse strains and can cause persistent infections even in immunocompetent mice. Despite the fact that immunocompetent mice are generally asymptomatic, the possibility that MNV infection might alter immune responses makes its eradication a potentially useful goal for many facilities. Initial attempts by others to use a strategy of testing and culling were unsuccessful, whereas complete depopulation and facility decontamination was successful. However, these measures may be impractical, and finding less drastic approaches seemed prudent. Based on a report that cross-fostering of pups from MNV-positive mothers to MNV-negative ones could be successful in experimental MNV infection, we undertook a comprehensive fostering program using Swiss Webster mothers, careful sanitary measures, and fecal PCR testing to eradicate the virus from a mouse colony recently infected with MNV. We successfully decontaminated 17 of 18 (94%) litters and managed to prevent spread when a new MNV-infected mouse strain entered quarantine at our facility. These results suggest that cross-fostering, when performed in a setting of excellent sanitary procedures, may be practical for the large number of mouse facilities in which MNV is endemic. C1 [Buxbaum, Laurence U.; DeRitis, Pierina C.; Chu, Niansheng; Conti, Pierre A.] Univ Penn, Sch Med, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Buxbaum, Laurence U.; Chu, Niansheng] Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. RP Buxbaum, LU (reprint author), Univ Penn, Sch Med, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. EM buxbaum@mail.med.upenn.edu FU Veterans Affairs Merit Award; Veterans Affairs Medical Center FX This work was funded by a Veterans Affairs Merit Award and by Veterans Affairs Medical Center facilities funding. We thank the Animal Research Facility staff for their careful attention to protocol in allowing our efforts to be successful. We also thank Dr Susan R Compton for advice on fostering procedures. The content of this article does not necessarily reflect the views of the Department of Veterans Affairs or of the US Government. NR 13 TC 6 Z9 6 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2011 VL 50 IS 4 BP 495 EP 499 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 875JP UT WOS:000299026500011 PM 21838978 ER PT J AU Lee, CG Boyko, EJ Strotmeyer, ES Lewis, CE Cawthon, PM Hoffman, AR Everson-Rose, SA Barrett-Connor, E Orwoll, ES AF Lee, Christine G. Boyko, Edward J. Strotmeyer, Elsa S. Lewis, Cora E. Cawthon, Peggy Mannen Hoffman, Andrew R. Everson-Rose, Susan A. Barrett-Connor, Elizabeth Orwoll, Eric S. CA Osteoporotic Fractures Men Study TI Association Between Insulin Resistance and Lean Mass Loss and Fat Mass Gain in Older Men without Diabetes Mellitus SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE older men; lean mass; fat mass; insulin resistance; body composition ID HOMEOSTASIS MODEL ASSESSMENT; HIGH FASTING INSULIN; BODY-COMPOSITION; WEIGHT-GAIN; OSTEOPOROTIC FRACTURES; METABOLIC SYNDROME; GLUCOSE-TOLERANCE; ELDERLY-MEN; LOWER RATES; AMINO-ACID AB OBJECTIVES: To examine the associations between insulin resistance and changes in body composition in older men without diabetes mellitus. DESIGN: Longitudinal cohort study of older men participating in the Osteoporotic Fractures in Men (MrOS) study. SETTING: Six U.S. clinical centers. PARTICIPANTS: Three thousand one hundred thirty-two ambulatory men aged 65 and older at baseline. MEASUREMENTS: Baseline insulin resistance was calculated for men without diabetes mellitus using the homeostasis model assessment of insulin resistance (HOMA-IR). Total lean, appendicular lean, total fat, and truncal fat mass were measured using dual energy X-ray absorptiometry scans at baseline and 4.6 perpendicular to 0.3 years later in 3,132 men with HOMA-IR measurements. RESULTS: There was greater loss of weight, total lean mass, and appendicular lean mass and less gain in total fat mass and truncal fat mass with increasing quartiles of HOMA-IR (P<.001 for trend). Insulin-resistant men in the highest quartile had higher odds of 5% or more loss of weight (odds ratio (OR) = 1.88, 95% confidence interval (CI) = 1.46-2.43), total lean mass (OR = 2.09, 95% CI = 1.60-2.73) and appendicular lean mass (OR = 1.57, 95% CI = 1.27-1.95) and lower odds of 5% or more gain in total fat mass (OR = 0.56, 95% CI = 0.45-0.68) and truncal fat mass (OR = 0.52, 95% CI = 0.42-0.64) than those in the lowest quartile. These findings remained significant after accounting for age, site, baseline weight, physical activity, and change in physical activity. These associations were also independent of other metabolic syndrome features and medications. CONCLUSION: Greater lean mass loss and lower fat mass gain occurred in insulin-resistant men without diabetes mellitus than in insulin-sensitive men. Insulin resistance may accelerate age-related sarcopenia. J Am Geriatr Soc 59:1217-1224, 2011. C1 [Lee, Christine G.; Orwoll, Eric S.] Oregon Hlth & Sci Univ, Dept Med, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97239 USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gen Internal Med, Seattle, WA USA. [Strotmeyer, Elsa S.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Lewis, Cora E.] Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. [Cawthon, Peggy Mannen] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Hoffman, Andrew R.] Stanford Univ, Dept Med, Div Endocrinol Gerontol & Metab, Palo Alto, CA 94304 USA. [Everson-Rose, Susan A.] Univ Minnesota, Dept Med, Div Gen Internal Med, Minneapolis, MN 55455 USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family & Prevent Med, Div Epidemiol, La Jolla, CA 92093 USA. RP Lee, CG (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Endocrinol Diabet & Clin Nutr, 3181 SW Sam Jackson Pk Rd,CR 113, Portland, OR 97239 USA. EM leechr@ohsu.edu RI Strotmeyer, Elsa/F-3015-2014 OI Strotmeyer, Elsa/0000-0002-4093-6036; Orwoll, Eric/0000-0002-8520-7355; Boyko, Edward/0000-0002-3695-192X FU National Institutes of Health [P30DK17047]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institute on Aging (NIA); National Center for Research Resources (NCRR); NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01 AG027810, UL1 RR024140]; American Diabetes Association [1-04-JF-46] FX MrOS is supported by funding from the National Institutes of Health. The following institutes provide 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 NIH Roadmap for Medical Research under Grants U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01 AG027810, and UL1 RR024140. Additional support was provided by the Veterans Affairs Puget Sound and Diabetes Endocrinology Research Center at the University of Washington supported by NIH Grant P30DK17047 to E.J.B. and American Diabetes Association Grant 1-04-JF-46 to E.S.S. NR 38 TC 44 Z9 46 U1 2 U2 4 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 JUL PY 2011 VL 59 IS 7 BP 1217 EP 1224 DI 10.1111/j.1532-5415.2011.03472.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 791VT UT WOS:000292696100007 PM 21718263 ER PT J AU Chung, B Dopheide, JA Gregerson, P AF Chung, Bosun Dopheide, Julie A. Gregerson, Paul TI Psychiatric Pharmacist and Primary Care Collaboration at a Skid-Row Safety-Net Clinic SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE primary care; psychiatry; pharmacist; safety-net practices ID OUTCOMES; SERVICES; IMPACT AB Purpose: There is limited access to psychiatric medication follow-up services at safety-net clinics serving the largely homeless minority population of Los Angeles' skid-row district. This paper describes the process of establishing a pharmacist-run psychiatric medication management service, the types of interventions provided by the psychiatric pharmacist, and patient and provider satisfaction with the service. Methods: The establishment of a collaborative practice agreement between primary care physicians and psychiatric pharmacists is described along with the patient demographics and types of pharmacist interventions. Primary care physicians were surveyed regarding their comfort level with managing psychiatric illness and prescribing psychotropic medications. They were also asked about their opinion of psychiatric pharmacist medication management services. An anonymous patient satisfaction survey was also administered. Results: The development of psychiatric pharmacy services is described. The types of interventions included initiating drug therapy, adjusting dosages, discontinuing drug therapy, and providing medication education. Primary care providers were not comfortable in providing psychiatric medication follow-up for patients beyond uncomplicated depression and anxiety disorders. They expressed an overall positive view of psychiatric pharmacist services for their patients with established psychiatric diagnoses. Patient satisfaction ratings were high. Conclusions: A psychiatric pharmacist-run medication management service in collaboration with primary care providers can improve access to mental health services in safety-net clinics with good provider and patient satisfaction. C1 [Chung, Bosun; Dopheide, Julie A.] Univ So Calif, Sch Pharm, Los Angeles, CA 90089 USA. [Chung, Bosun] Healthcare, Vet Adm Greater Los Angeles, Los Angeles, CA USA. [Gregerson, Paul] JWCH Inc Weingart, Ctr Community Hlth, Los Angeles, CA USA. RP Dopheide, JA (reprint author), Univ So Calif, Sch Pharm, 1985 Zonal Ave, Los Angeles, CA 90089 USA. EM dopheide@usc.edu NR 12 TC 1 Z9 1 U1 1 U2 3 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD JUL PY 2011 VL 103 IS 7 BP 567 EP 574 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 829SY UT WOS:000295605800003 PM 21999031 ER PT J AU Pizer, SD Prentice, JC AF Pizer, Steven D. Prentice, Julia C. TI Time is money: Outpatient waiting times and health insurance choices of elderly veterans in the United States SO JOURNAL OF HEALTH ECONOMICS LA English DT Article DE Outpatient waiting times; Insurance choice; Medicare ID CARE SERVICES; MEDICARE; ACCESS; BENEFITS; QUALITY; DEMAND; DESIGN; MARKET; IMPACT; COSTS AB Growth in the number of days between an appointment request and the actual appointment reduces demand. Although such waiting times are relatively low in the US, current policy initiatives could cause them to increase. We estimate multiple-equation models of physician utilization and insurance plan choice for Medicare-eligible veterans. We find that a 10% increase in VA waiting times increases demand for Medigap insurance by 5%, implying that a representative patient would be indifferent between waiting an average of 5 more days for VA appointments and paying $300 more in annual premium. Published by Elsevier B.V. C1 [Pizer, Steven D.; Prentice, Julia C.] US Dept Vet Affairs, Boston, MA 02130 USA. [Pizer, Steven D.; Prentice, Julia C.] Boston Univ, Boston, MA 02130 USA. RP Pizer, SD (reprint author), US Dept Vet Affairs, 150 S Huntington Ave,Mail Stop 152H, Boston, MA 02130 USA. EM pizer@bu.edu FU Health Services Research and Development Service of the U.S. Department of Veterans Affairs [IAD 06-112]; Changes in Health Care Financing and Organization (HCFO) Initiative of the Robert Wood Johnson Foundation [62967] FX This research was supported by grants from the Health Services Research and Development Service of the U.S. Department of Veterans Affairs (Grant No. IAD 06-112) and from the Changes in Health Care Financing and Organization (HCFO) Initiative of the Robert Wood Johnson Foundation (Grant No. 62967). The views expressed are those of the authors and do not necessarily reflect the official positions of the U.S. Department of Veterans Affairs, the Robert Wood Johnson Foundation, or Boston University. The authors would like to thank Tom McGuire and participants in the BU/Harvard/MIT Health Economics Seminar Series as well as two anonymous reviewers for many helpful comments. NR 34 TC 7 Z9 7 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-6296 J9 J HEALTH ECON JI J. Health Econ. PD JUL PY 2011 VL 30 IS 4 BP 626 EP 636 DI 10.1016/j.jhealeco.2011.05.004 PG 11 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 813TQ UT WOS:000294393500003 PM 21641062 ER PT J AU Howard, TE AF Howard, T. E. TI Factor VIII gene haplotype and inhibitor development SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Howard, T. E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol, Los Angeles, CA USA. [Howard, T. E.] Vet Affairs Greater Los Angeles Healthcare Syst, Lab Med, Los Angeles, CA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI BP 1 EP 1 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 800DU UT WOS:000293340800002 ER PT J AU Erten-Lyons, D Wilmot, B Anur, P McWeeney, S Westaway, SK Silbert, L Kramer, P Kaye, J AF Erten-Lyons, Deniz Wilmot, Beth Anur, Pavana McWeeney, Shannon Westaway, Shawn K. Silbert, Lisa Kramer, Patricia Kaye, Jeffrey CA Alzheimer's Dis Neuroimaging TI Microcephaly Genes and Risk of Late-onset Alzheimer Disease SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease; microcephaly genes; cognitive reserve ID ONGOING ADAPTIVE EVOLUTION; BRAIN SIZE; MOLECULAR EVOLUTION; HEAD CIRCUMFERENCE; MAJOR DETERMINANT; OLDEST-OLD; ASPM GENE; ASSOCIATION; POPULATION; DEMENTIA AB Brain development in the early stages of life has been suggested to be one of the factors that may influence an individual's risk of Alzheimer disease (AD) later in life. Four microcephaly genes, which regulate brain development in utero and have been suggested to play a role in the evolution of the human brain, were selected as candidate genes that may modulate the risk of AD. We examined the association between single nucleotide polymorphisms tagging common sequence variations in these genes and risk of AD in two case-control samples. We found that the G allele of rs2442607 in microcephalin 1 was associated with an increased risk of AD (under an additive genetic model, P = 0.01; odds ratio = 3.41; confidence interval, 1.77-6.57). However, this association was not replicated using another case-control sample research participants from the Alzheimer Disease Neuroimaging Initiative. We conclude that the common variations we measured in the 4 microcephaly genes do not affect the risk of AD or that their effect size is small. C1 [Erten-Lyons, Deniz; Kaye, Jeffrey] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. [Erten-Lyons, Deniz; Westaway, Shawn K.; Silbert, Lisa; Kramer, Patricia; Kaye, Jeffrey] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Wilmot, Beth; Anur, Pavana; McWeeney, Shannon] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Ctr, Portland, OR 97201 USA. [Wilmot, Beth; McWeeney, Shannon] Oregon Hlth & Sci Univ, Div Bioinformat & Computat Biol, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [McWeeney, Shannon] Oregon Hlth & Sci Univ, Dept Publ Hlth & Preventat Med, Div Biostat, Portland, OR 97201 USA. RP Erten-Lyons, D (reprint author), NIA, Layton Aging & Alzheimers Dis Ctr, 3181 SW Sam Jackson Pk Rd,CR 131, Portland, OR 97239 USA. EM ertenlyo@ohsu.edu RI Scharre, Douglas/E-4030-2011 OI Kaye, Jeffrey/0000-0002-9971-3478; McWeeney, Shannon/0000-0001-8333-6607; Silbert, Lisa/0000-0002-4525-0068 FU Office of Research and Development, Department of Veterans Affairs, National Institutes of Health [AG08017, MO1 RR000334, UL1 RR024140]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering; Northern California Institute for Research and Education; NIH [P30 AG010129, K01 AG030514]; Dana Foundation FX Supported by Merit Review Grant and Research Career Development Award, Office of Research and Development, Department of Veterans Affairs, National Institutes of Health (AG08017, MO1 RR000334, UL1 RR024140), Alzheimer Tax Check-off Grant. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; AstraZeneca AB; Bayer Schering Pharma AG; Bristol-Myers Squibb; Eisai Global Clinical Development; Elan Corporation; Genentech; GE Healthcare; GlaxoSmithKline; Innogenetics; Johnson and Johnson; Eli Lilly and Co.; Medpace, Inc.; Merck and Co., Inc.; Novartis AG; Pfizer Inc.; F. Hoffman-La Roche; Schering-Plough; Synarc, Inc.; and nonprofit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. NR 34 TC 0 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JUL-SEP PY 2011 VL 25 IS 3 BP 276 EP 282 DI 10.1097/WAD.0b013e31820a1d32 PG 7 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 811JW UT WOS:000294206600013 PM 21297427 ER PT J AU Boockvar, KS Santos, SL Kushniruk, A Johnson, C Nebeker, JR AF Boockvar, Kenneth S. Santos, Susan L. Kushniruk, Andre Johnson, Christopher Nebeker, Jonathan R. TI Medication Reconciliation: Barriers and Facilitators from the Perspectives of Resident Physicians and Pharmacists SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID ADVERSE DRUG EVENTS AB BACKGROUND: Medication reconciliation can prevent medication errors and harm when patients transition between hospital and other care settings. Though a Joint Commission hospital Patient Safety Goal since 2006, organizations continue to have difficulty implementing the process. OBJECTIVE: To determine factors that influence performance of medication reconciliation in a hospital setting with a computerized medication reconciliation tool. DESIGN: Cognitive task analysis (CTA) and focus group interviews. SETTING: Urban, academic, tertiary-care Veterans Affairs medical center. PARTICIPANTS: Internal medicine house staff physicians (n = 23) and inpatient staff pharmacists (n = 12). MEASUREMENTS: CTA participants verbalized their thoughts while they completed medication reconciliation with the computerized tool. Focus group participants described medication reconciliation's purpose and effectiveness, how they completed the task, and its barriers and facilitators. Interviews were recorded and analyzed using social science methods for analyzing qualitative data. RESULTS: Participants agreed that a central goal of medication reconciliation is to prevent prescribing errors, but disagreed about whether it achieves this goal. Computerization facilitated the task, but participants said that computers and patients can be unreliable sources of information. Participants varied in how they sequenced components of the task. When time was limited, physicians considered other responsibilities higher priority. Both physicians and pharmacists expressed low self-efficacy, ie, low perceived capability to achieve the objectives of the process. CONCLUSION: Key barriers to medication reconciliation are unreliable sources of medication information and tasks that compete for providers' time and attention that they consider higher priority. Addressing these barriers while increasing providers' self-efficacy might improve medication reconciliation and its outcomes. Journal of Hospital Medicine 2011;6:329-337. (C) 2011 Society of Hospital Medicine C1 [Boockvar, Kenneth S.] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. [Boockvar, Kenneth S.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA. [Boockvar, Kenneth S.] Jewish Home Lifecare, New York, NY USA. [Santos, Susan L.] VA New Jersey Hlth Care Syst, E Orange, NJ USA. [Santos, Susan L.] Univ Med & Dent New Jersey, Dept Hlth Educ & Behav Sci, New Brunswick, NJ USA. [Kushniruk, Andre] Univ Victoria, Sch Hlth Informat Sci, Victoria, BC, Canada. [Johnson, Christopher] Texas A&M Hlth Sci Ctr, Dept Hlth Policy & Management, College Stn, TX USA. [Johnson, Christopher] VA S Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA. [Johnson, Christopher] Michael E Debakey VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Nebeker, Jonathan R.] Univ Utah, Salt Lake City, UT USA. [Nebeker, Jonathan R.] VA Geriatr Res Educ & Clin Ctr, Salt Lake City, UT USA. RP Boockvar, KS (reprint author), James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU VA Health Services Research and Development Service; Greenwall Foundation FX This work was supported by VA Health Services Research and Development Service. Dr. Boockvar is also supported by the Greenwall Foundation. The authors have no conflicts of interest to disclose. NR 20 TC 21 Z9 22 U1 0 U2 8 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 JUL-AUG PY 2011 VL 6 IS 6 BP 329 EP 337 DI 10.1002/jhm.891 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 810RA UT WOS:000294143600003 PM 21834114 ER PT J AU Farber, JI Korc-Grodzicki, B Du, QL Leipzig, RM Siu, AL AF Farber, Jeffrey I. Korc-Grodzicki, Beartriz Du, Qingling Leipzig, Rosanne M. Siu, Albert L. TI Operational and Quality Outcomes of a Mobile Acute Care for the Elderly Service SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; OLDER PATIENTS; FUNCTIONAL OUTCOMES; MEDICAL UNIT; INTERVENTION; COSTS AB BACKGROUND: The traditional acute care for the elderly (ACE) unit has demonstrated improved functional outcomes without increased costs or changes in length of stay (LOS). It is, however, limited in scope to patients cared for on a fixed geographical unit. OBJECTIVE: To compare operational and quality outcomes for patients cared for on a mobile ACE (MACE) service to those cared for on a unit-based ACE service and matched controls on other general medical services. DESIGN: Retrospective cohort study with propensity-score matching. SETTING: An urban academic medical center. PATIENTS: A total of 8094 hospitalized adults >64 years old admitted to an ACE, MACE, and general medical services from July 2006 to June 2009. INTERVENTION: An interdisciplinary MACE service composed of a geriatrician-hospitalist, fellow, nurse coordinator, and social worker. MEASUREMENTS: LOS, total cost, 7- and 30-day readmission rates, and in-hospital mortality. RESULTS: Mean LOS and total cost were significantly lower for patients in the MACE service compared with the ACE unit service (5.8 vs 7.9 days, P < 0.001, and $10,315 vs $13,187, P = 0.002) and compared with propensity-score matched controls during the second year of operation (5.6 vs 7.2 days, P < 0.001, and $10,693 vs $15,636, P < 0.001). In-hospital mortality and 7- and 30-day readmission rates were similar in all groups. CONCLUSIONS: A mobile ACE service may result in reduced LOS and lower costs with no change in in-hospital mortality or 7- or 30-day readmission rates when compared with standard medical service and a traditional unit-based ACE service. Journal of Hospital Medicine 2011;6:358-363. (C) 2011 Society of Hospital Medicine C1 [Farber, Jeffrey I.; Du, Qingling; Leipzig, Rosanne M.; Siu, Albert L.] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Korc-Grodzicki, Beartriz] Mem Sloan Kettering Canc Ctr, Dept Med, Geriatr Serv, New York, NY 10021 USA. [Siu, Albert L.] Geriatr Res Educ & Clin Ctr, James J Peters VA Med Ctr, New York, NY USA. RP Farber, JI (reprint author), Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM jeffrey.farber@mssm.edu OI Korc-Grodzicki, Beatriz/0000-0003-0673-4606 FU Health Resources and Services Administration, US Department of Health and Human Services; National Institute on Aging; John A. Hartford Foundation FX Dr. Farber received grant support from a Geriatric Academic Career Award from the Health Resources and Services Administration, US Department of Health and Human Services. Dr. Sin received grant support from the National Institute on Aging Midcareer Investigator Award in Patient-Oriented Research.; Dr. Kore-Grodzicki received grant support from the John A. Hartford Foundation. NR 13 TC 5 Z9 5 U1 0 U2 5 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 JUL-AUG PY 2011 VL 6 IS 6 BP 358 EP 363 DI 10.1002/jhm.878 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 810RA UT WOS:000294143600007 PM 21834119 ER PT J AU Grant, JS Keltner, NL Eagerton, G AF Grant, Joan S. Keltner, Norman L. Eagerton, Greg TI Simulation to Enhance Care of Patients with Psychiatric and Behavioral Issues Use in Clinical Settings SO JOURNAL OF PSYCHOSOCIAL NURSING AND MENTAL HEALTH SERVICES LA English DT Article ID STANDARDIZED PATIENTS; EDUCATION; SKILLS AB Nurses with a medical-surgical clinical focus often care for patients with psychiatric and behavioral issues in acute care hospitals. This article describes how hospital staff and nursing and theater department faculty joined forces to develop realistic simulated psychiatric scenarios for use by practicing nurses. C1 [Grant, Joan S.; Keltner, Norman L.] Univ Alabama, Birmingham Sch Nursing, Birmingham, AL 35205 USA. [Eagerton, Greg] Birmingham Vet Affairs Med Ctr, Patient Care Nursing Serv, Birmingham, AL USA. RP Keltner, NL (reprint author), Univ Alabama, Birmingham Sch Nursing, NB Room 302,1530 3rd Ave S, Birmingham, AL 35205 USA. EM nkeltner@uab.edu OI Grant, Joan/0000-0001-6000-4060 NR 24 TC 3 Z9 3 U1 1 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0279-3695 J9 J PSYCHOSOC NURS MEN JI J. Psychosoc. Nurs. Ment. Health Serv. PD JUL PY 2011 VL 49 IS 7 BP 43 EP 49 DI 10.3928/02793695-20110609-01 PG 7 WC Nursing SC Nursing GA 811ZV UT WOS:000294258400011 PM 21702427 ER PT J AU Singh, JA Taylor, WJ Simon, LS Khanna, PP Stamp, LK McQueen, FM Neogi, T Gaffo, AL Becker, MA MacDonald, PA Dabbous, O Strand, V Dalbeth, ND Aletaha, D Edwards, NL Schumacher, HR AF Singh, Jasvinder A. Taylor, Will J. Simon, Lee S. Khanna, Puja P. Stamp, Lisa K. McQueen, Fiona M. Neogi, Tuhina Gaffo, Angelo L. Becker, Michael A. MacDonald, Patricia A. Dabbous, Omar Strand, Vibeke Dalbeth, Nicola D. Aletaha, Daniel Edwards, N. Lawrence Schumacher, H. Ralph, Jr. TI Patient-reported Outcomes in Chronic Gout: A Report from OMERACT 10 SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE PATIENT-REPORTED OUTCOMES; CHRONIC GOUT; VALIDATION; PAIN; PATIENT GLOBAL; FUNCTIONAL LIMITATION ID QUESTIONNAIRE DISABILITY INDEX; QUALITY-OF-LIFE; SERUM URATE; HYPERURICEMIA; ALLOPURINOL; FEBUXOSTAT AB Objective. To summarize the endorsement of measures of patient-reported outcome (PRO) domains in chronic gout at the 2010 Outcome Measures in Rheumatology Meeting (OMERACT 10). Methods. During the OMERACT 10 gout workshop, validation data were presented for key PRO domains including pain [pain by visual analog scale (VAS)], patient global (patient global VAS), activity limitation [Health Assessment Questionnaire-Disability Index (HAQ-DI)], and a disease-specific measure, the Gout Assessment Questionnaire version 2.0 (GAQ v2.0). Data were presented on all 3 aspects of the OMERACT filters of truth, discrimination, and feasibility. One PRO, health-related quality of life measurement with the Medical Outcomes Study Short-form 36 (SF-36), was previously endorsed at OMERACT 9. Results. One measure for each of the 3 PRO of pain, patient global, and activity limitation was endorsed by > 70% of the OMERACT delegates to have appropriate validation data. Specifically, pain measurement by VAS was endorsed by 85%, patient global assessment by VAS by 73%, and activity limitation by HAQ-DI by 71%. GAQ v2.0 received 30% vote and was not endorsed due to several concerns including low internal consistency and lack of familiarity with the measure. More validation studies are needed for this measure. Conclusion. With the endorsement of one measure each for pain, patient global, SF-36, and activity limitation, all 4 PRO for chronic gout have been endorsed. Future validation studies are needed for the disease-specific measure, GAQ v2.0. Validation for PRO for acute gout will be the focus of the next validation exercise for the OMERACT gout group. (J Rheumatol 2011;38:1452-7; doi:10.3899/jrheum.110271) C1 [Singh, Jasvinder A.] Birmingham Vet Affairs VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.; Gaffo, Angelo L.] Univ Birmingham, Dept Med, Div Rheumatol, Birmingham, AL USA. [Singh, Jasvinder A.; Gaffo, Angelo L.] Univ Birmingham, Div Epidemiol, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Hlth Sci Res, Rochester, MN USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. [Taylor, Will J.] Univ Otago, Dept Med, Wellington, New Zealand. [Simon, Lee S.] SDG LLC, Cambridge, MA USA. [Khanna, Puja P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. Univ Otago, Dept Med, Christchurch, New Zealand. [Stamp, Lisa K.; McQueen, Fiona M.] Univ Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland 1, New Zealand. [Neogi, Tuhina] Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. [Becker, Michael A.] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [MacDonald, Patricia A.] Takeda Global Res & Dev Ctr Inc, Deerfield, IL USA. [Dabbous, Omar] Takeda Pharmaceut Int Inc, Deerfield, IL USA. [Strand, Vibeke] Stanford Univ, Palo Alto, CA 94304 USA. [Dalbeth, Nicola D.] Univ Auckland, Dept Med, Auckland 1, New Zealand. [Aletaha, Daniel] Med Univ, Div Rheumatol, Vienna, Austria. [Edwards, N. Lawrence] Univ Florida, Dept Med, Gainesville, FL USA. [Schumacher, H. Ralph, Jr.] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph, Jr.] VA Med Ctr, Philadelphia, PA USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006; Neogi, Tuhina/0000-0002-9515-1711 FU National Institutes of Health (NIH) [1 KL2 RR024151-01, AR0557127, P60 AR047785]; NIH/NIAMS [UO1 AR057936]; American College of Rheumatology; Allergan; Takeda; Savient; Wyeth; Amgen; URL pharmaceuticals; Novartis; Regeneron; Pfizer FX Supported by a National Institutes of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) to Dr. Singh, and by resources and facilities at the Birmingham VA Medical Center, Alabama, USA. Dr. Neogi was supported by awards from the NIH K23 (AR0557127) and P60 AR047785. Dr. Khanna was supported by research grants from the NIH/NIAMS (UO1 AR057936) and an American College of Rheumatology REF Clinical Investigator Award. Data were obtained from Savient Pharmaceuticals and Takeda Global Research and Development. Dr. Singh has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth and Amgen; and consultant fees from Savient, URL pharmaceuticals, and Novartis. Ms MacDonald is an employee of Takeda Global Research and Development. Dr. Dabbous is an employee of Takeda Pharmaceuticals International Inc. Dr. Schumacher has received consulting fees from Takeda, Savient, Regeneron, Novartis, and Pfizer. Dr. Becker has been a consultant for Takeda, Savient, BioCryst, URL/Pharma, Ardea, and Regeneron. Dr. Strand served as a consultant to Savient and Takeda Pharmaceuticals. Dr. Edwards has received consultant fees from Takeda and Savient. Views expressed in this article are the authors' and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 22 TC 34 Z9 35 U1 3 U2 7 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2011 VL 38 IS 7 BP 1452 EP 1457 DI 10.3899/jrheum.110271 PG 6 WC Rheumatology SC Rheumatology GA 796HE UT WOS:000293041600036 PM 21724715 ER PT J AU Dalbeth, N McQueen, FM Singh, JA MacDonald, PA Edwards, NL Schumacher, HR Simon, LS Stamp, LK Neogi, T Gaffo, AL Khanna, PP Becker, MA Taylor, WJ AF Dalbeth, Nicola McQueen, Fiona M. Singh, Jasvinder A. MacDonald, Patricia A. Edwards, N. Lawrence Schumacher, H. Ralph, Jr. Simon, Lee S. Stamp, Lisa K. Neogi, Tuhina Gaffo, Angelo L. Khanna, Puja P. Becker, Michael A. Taylor, William J. TI Tophus Measurement as an Outcome Measure for Clinical Trials of Chronic Gout: Progress and Research Priorities SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE GOUT; TOPHUS; OUTCOME MEASURE ID QUANTITATIVE-ANALYSIS; PHYSICAL MEASUREMENT; COMPUTED-TOMOGRAPHY; ALLOPURINOL; FEBUXOSTAT; URATE; HYPERURICEMIA; DOMAINS AB Despite the recognition that tophus regression is an important outcome measure in clinical trials of chronic gout, there is no agreed upon method of tophus measurement. A number of methods have been used in clinical trials of chronic gout, from simple physical measurement techniques to more complex advanced imaging methods. This article summarizes methods of tophus measurement and discusses their properties. Physical measurement using Vernier calipers meets most aspects of the Outcome Measures in Rheumatology (OMERACT) filter. Rigorous testing of the complex methods, particularly with respect to reliability and sensitivity to change, is needed to determine the appropriate use of these methods. Further information is also required regarding which method of physical measurement is best for use in future clinical trials. The need to develop and test a patient-reported outcome measure of tophus burden is also highlighted. (J Rheumatol 2011;38:1458-61; doi:10.3899/jrheum.110272) C1 [Dalbeth, Nicola; McQueen, Fiona M.] Univ Auckland, Fac Med & Hlth Sci, Auckland 1, New Zealand. [Singh, Jasvinder A.; Gaffo, Angelo L.] Birmingham Vet Affairs VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.; Gaffo, Angelo L.] Univ Alabama, Birmingham, AL USA. [MacDonald, Patricia A.] Takeda Global Res & Dev, Clin Sci, Deerfield, IL USA. [Edwards, N. Lawrence] Univ Florida, Dept Med, Gainesville, FL USA. [Schumacher, H. Ralph, Jr.] Univ Penn, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph, Jr.] VA Med Ctr, Philadelphia, PA USA. [Simon, Lee S.] SDG LLC, Med, Cambridge, MA USA. [Stamp, Lisa K.] Univ Otago, Dept Med, Christchurch, New Zealand. [Neogi, Tuhina] Boston Univ, Sch Med, Boston, MA 02118 USA. [Khanna, Puja P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Becker, Michael A.] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [Taylor, William J.] Univ Otago, Dept Med, Wellington, New Zealand. RP Dalbeth, N (reprint author), Univ Auckland, Fac Med & Hlth Sci, Auckland 1, New Zealand. EM n.dalbeth@auckland.ac.nz OI singh, jasvinder/0000-0003-3485-0006; Neogi, Tuhina/0000-0002-9515-1711 FU American College of Rheumatology REF; NIAMS [5K23AR55127]; Takeda; Novartis; Allergan; Savient; Wyeth; Amgen; URL Pharmaceuticals; BioCryst; Ardea; Regeneron FX Supported by resources and use of facilities at the Birmingham VA Medical Center, Alabama, USA (Dr. Singh). Dr. Khanna is the recipient of an American College of Rheumatology REF Clinical Investigator Award (Quality of Life and Healthcare Utilization in Chronic Gout). Dr. Neogi is supported by NIAMS 5K23AR55127. Dr. Dalbeth has received consultant fees from Takeda and Novartis. Dr. Singh has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth, and Amgen; and consultant fees from Savient, URL Pharmaceuticals, and Novartis. Dr. Simon has served on the Board of Directors for Savient Pharmaceuticals and as a consultant for Takeda. Ms MacDonald is an employee of Takeda. Dr. Becker has received consultant fees from Takeda, Savient, BioCryst, URL Pharmaceuticals, Ardea, and Regeneron. NR 17 TC 14 Z9 15 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2011 VL 38 IS 7 BP 1458 EP 1461 DI 10.3899/jrheum.110272 PG 4 WC Rheumatology SC Rheumatology GA 796HE UT WOS:000293041600037 PM 21724716 ER PT J AU Stamp, LK Khanna, PP Dalbeth, N Boers, M Maksymowych, WP Schumacher, HR Becker, MA MacDonald, PA Edwards, NL Singh, JA Simon, LS McQueen, FM Neogi, T Gaffo, AL Strand, V Taylor, WJ AF Stamp, Lisa K. Khanna, Puja P. Dalbeth, Nicola Boers, Maarten Maksymowych, Walter P. Schumacher, H. Ralph, Jr. Becker, Michael A. MacDonald, Patricia A. Edwards, N. Lawrence Singh, Jasvinder A. Simon, Lee S. McQueen, Fiona M. Neogi, Tuhina Gaffo, Angelo L. Strand, Vibeke Taylor, William J. TI Serum Urate in Chronic Gout - Will It Be the First Validated Soluble Biomarker in Rheumatology? SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE SERUM URATE; GOUT; BIOMARKER ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; URIC-ACID LEVEL; RISK-FACTORS; HYPERURICEMIA; POPULATION; CONSUMPTION; DISEASE; CONSTITUENTS; ALLOPURINOL AB Objective. To summarize evidence for and endorsement of serum urate (SU) as having fulfilled the OMERACT filter as a soluble biomarker in chronic gout at the 2010 Outcome Measures in Rheumatology Meeting (OMERACT 10). Methods. Data were presented to support the use of SU as a soluble biomarker in chronic gout and specifically the ability to utilize it to predict future patient-reported outcomes. Results. SU was accepted as having fulfilled the OMERACT filter by 78% of voters. However, consensus was not obtained regarding its use as a soluble biomarker in chronic gout. Although the majority of the criteria for a soluble biomarker were fulfilled, the key criterion of association of the biomarker with outcomes was not agreed upon. It was agreed that the appropriate choice of endpoint must be linked to its clinical importance to the individual with the disorder and its temporal relationship to the intervention. Appropriate outcomes in chronic gout may therefore include gout flares, reduction in tophi, and patient-reported outcomes. Conclusion. SU is a critical outcome measure. It has the potential to fulfil criteria for a soluble biomarker. Further analyses of existing data from randomized controlled trials will be required to determine whether SU can predict future important outcomes, in particular disability. (J Rheumatol 2011;38:1462-6; doi:10.3899/jrheum.110273) C1 [Stamp, Lisa K.] Univ Otago, Dept Med, Christchurch, New Zealand. [Khanna, Puja P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Dalbeth, Nicola; McQueen, Fiona M.] Univ Auckland, Fac Med & Hlth Sci, Auckland 1, New Zealand. [Boers, Maarten] Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. [Maksymowych, Walter P.] Univ Alberta, Dept Med, Edmonton, AB, Canada. [Schumacher, H. Ralph, Jr.] Univ Penn, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph, Jr.] Vet Affairs VA Med Ctr, Philadelphia, PA USA. [Becker, Michael A.] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [MacDonald, Patricia A.] Takeda Global Res & Dev, Deerfield, IL USA. [Edwards, N. Lawrence] Univ Florida, Dept Med, Gainesville, FL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.; Gaffo, Angelo L.] Univ Alabama, Dept Med, Div Rheumatol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Gaffo, Angelo L.] Univ Alabama, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Hlth Sci Res, Rochester, MN USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. [Simon, Lee S.] SDG LLC, Cambridge, MA USA. [Neogi, Tuhina] Boston Univ, Sch Med, Boston, MA 02118 USA. [Strand, Vibeke] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Taylor, William J.] Univ Otago, Wellington, New Zealand. RP Stamp, LK (reprint author), Univ Otago, Dept Med, Christchurch, New Zealand. EM lisa.stamp@cdhb.govt.nz OI singh, jasvinder/0000-0003-3485-0006; Neogi, Tuhina/0000-0002-9515-1711 FU National Institutes of Health (NIH) [1 KL2 RR024151-01, K23 (AR0557127), P60 AR047785]; NIH/NIAMS [UO1 AR057936]; American College of Rheumatology REF; Takeda; Savient; Regeneron; Novartis; Pfizer; Allergan; Wyeth; Amgen; URL Pharmaceuticals FX Supported by National Institutes of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) to Dr. Singh; and resources and use of facilities at the Birmingham VA Medical Center, Alabama, USA. Dr. Neogi was supported by awards from the NIH K23 (AR0557127) and P60 AR047785. Dr. Khanna was supported by research grants from the NIH/NIAMS (UO1 AR057936) and an American College of Rheumatology REF Clinical Investigator Award. Data were obtained from the Savient Pharmaceuticals and the Takeda Global Research and Development. Dr. Schumacher has received consulting fees from Takeda, Savient, Regeneron, Novartis, and Pfizer. Dr. Becker has been a consultant for Takeda, Savient, BioCryst, URL Pharmaceuticals, Ardea, and Regeneron. Ms MacDonald is an employee of Takeda Global Research and Development. Dr. Edwards has received consultant fees from Takeda and Savient. Dr. Singh has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth and Amgen; and consultant fees from Savient, URL Pharmaceuticals, and Novartis. Dr. Simon has served on the Board of Directors for Savient Pharmaceuticals and as a consultant for Takeda. Dr. Strand has served as a consultant to Savient and Takeda Pharmaceuticals. NR 40 TC 8 Z9 8 U1 0 U2 6 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2011 VL 38 IS 7 BP 1462 EP 1466 DI 10.3899/jrheum.110273 PG 5 WC Rheumatology SC Rheumatology GA 796HE UT WOS:000293041600038 PM 21724717 ER PT J AU Taylor, WJ Singh, JA Saag, KG Dalbeth, N MacDonald, PA Edwards, NL Simon, LS Stamp, LK Neogi, T Gaffo, AL Khanna, PP Becker, MA Schumacher, HR AF Taylor, William J. Singh, Jasvinder A. Saag, Kenneth G. Dalbeth, Nicola MacDonald, Patricia A. Edwards, N. Lawrence Simon, Lee S. Stamp, Lisa K. Neogi, Tuhina Gaffo, Angelo L. Khanna, Puja P. Becker, Michael A. Schumacher, H. Ralph, Jr. TI Bringing It All Together: A Novel Approach to the Development of Response Criteria for Chronic Gout Clinical Trials SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE GOUT; RESPONSE CRITERIA; MULTICRITERIA DECISION-MAKING AB Objective. To review a novel approach for constructing composite response criteria for use in chronic gout clinical trials that implements a method of multicriteria decision-making. Methods. Preliminary work with paper patient profiles led to a restricted set of core-set domains that were examined using 1000Minds (TM) by rheumatologists with an interest in gout, and (separately) by OMERACT registrants prior to OMERACT 10. These results and the 1000Minds approach were discussed during OMERACT 10 to help guide next steps in developing composite response criteria. Results. There were differences in how individual indicators of response were weighted between gout experts and OMERACT registrants. Gout experts placed more weight upon changes in uric acid levels, whereas OMERACT registrants placed more weight upon reducing flares. Discussion highlighted the need for a "pain" domain to be included, for "worsening" to be an additional level within each indicator, for a group process to determine the decision-making within a 1000Minds exercise, and for the value of patient involvement. Conclusion. Although there was not unanimous support for the 1000Minds approach to inform the construction of composite response criteria, there is sufficient interest to justify ongoing development of this methodology and its application to real clinical trial data. (J Rheumatol 2011;38:1467-70; doi:10.3899/jrheum.110274) C1 [Taylor, William J.] Univ Otago, Dept Med, Wellington, New Zealand. [Singh, Jasvinder A.; Saag, Kenneth G.; Gaffo, Angelo L.] Birmingham Vet Affairs VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.; Saag, Kenneth G.; Gaffo, Angelo L.] Univ Alabama, Birmingham, AL USA. [Dalbeth, Nicola] Univ Auckland, Fac Med & Hlth Sci, Auckland 1, New Zealand. [MacDonald, Patricia A.] Takeda Global Res & Dev, Deerfield, IL USA. [Edwards, N. Lawrence] Univ Florida, Dept Med, Gainesville, FL USA. [Simon, Lee S.] SDG LLC, Cambridge, MA USA. [Stamp, Lisa K.] Univ Otago, Dept Med, Christchurch, New Zealand. [Neogi, Tuhina] Boston Univ, Sch Med, Boston, MA 02118 USA. [Khanna, Puja P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Becker, Michael A.] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [Schumacher, H. Ralph, Jr.] Univ Penn, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph, Jr.] VA Med Ctr, Philadelphia, PA USA. RP Taylor, WJ (reprint author), Univ Otago, Dept Med, Wellington, New Zealand. EM will.taylor@otago.ac.nz OI singh, jasvinder/0000-0003-3485-0006; Neogi, Tuhina/0000-0002-9515-1711 FU University of Otago; University of Pennsylvania; American College of Rheumatology REF; NIAMS [5K23AR55127]; Allergan; Takeda; Savient; Wyeth; Amgen; URL Pharmaceuticals; Novartis; Takeda, Savient, Regeneron; Pfizer FX Partially supported by a University of Otago Matched Funding Summer Scholarship and ACR-EULAR Grant through the University of Pennsylvania; also supported with resources and use of facilities at Birmingham VA Medical Center (Dr. Singh). Dr. Khanna is the recipient of an American College of Rheumatology REF Clinical Investigator Award (Quality of Life and Healthcare Utilization in Chronic Gout) and Co-Investigator on NIH/NIAMS 1 AR057936 (Development and Initial Validation of PROMIS G1 Distress Scale), Khanna, D; Spiegel B, co-principal investigators. Dr. Neogi is a recipient of NIAMS 5K23AR55127. Dr. Singh has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth, and Amgen; and consultant fees from Savient, URL Pharmaceuticals, and Novartis. Dr. Saag has received honoraria from Novartis, Amgen, and Lilly, has conducted clinical trials with Takeda, Novartis, and Regeneron, and serves on the Board of Directors of the Gout and Uric Acid Society. Ms MacDonald is an employee of Takeda Global Research and Development. Dr. Edwards has received consultant fees from Takeda and Savient. Dr. Simon has served on the Board of Directors for Savient Pharmaceuticals, and as a consultant for Takeda. Dr. Becker has been a consultant for Takeda, Savient, BioCryst, URL/Pharma, Ardea, and Regeneron. Dr. Schumacher has received consulting fees from Takeda, Savient, Regeneron, Novartis, and Pfizer. NR 15 TC 9 Z9 9 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2011 VL 38 IS 7 BP 1467 EP 1470 DI 10.3899/jrheum.110274 PG 4 WC Rheumatology SC Rheumatology GA 796HE UT WOS:000293041600039 PM 21724718 ER PT J AU Singh, JA Kundukulam, J Riddle, DL Strand, V Tugwell, P AF Singh, Jasvinder A. Kundukulam, Joseph Riddle, Daniel L. Strand, Vibeke Tugwell, Peter TI Early Postoperative Mortality Following Joint Arthroplasty: A Systematic Review SO JOURNAL OF RHEUMATOLOGY LA English DT Review DE MORTALITY; TOTAL KNEE ARTHROPLASTY; TOTAL HIP ARTHROPLASTY; SHORT-TERM MORTALITY ID TOTAL KNEE ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; QUALITY-OF-LIFE; UNITED-STATES; REVISION HIP; OUTCOMES; SURGEON; REPLACEMENT; ASSOCIATION; VOLUME AB Objective. To perform a systematic review of 30- and 90-day mortality rates in patients undergoing hip or knee arthroplasties. Methods. Five databases were searched for English-language studies of mortality in hip or knee arthroplasties and the following data were extracted: patient characteristics (age, sex, ethnicity), arthroplasty characteristics (unilateral vs bilateral, hip vs knee), system factors (hospital volume and surgeon volume), year of study, etc. Mortality rates were compared across variable categories; proportions were compared using relative risk ratios and 95% confidence intervals. Results. Out of 650 titles and abstracts, 80 studies qualified for analysis. Of these, 35%, 34%, and 31% of studies provided 30-, 90-, and > 90-day mortality rates. Overall 30-day mortality rates across all types of arthroplasties were 0.3%; 90-day, 0.7%. For those reports with specific rates, 30-day mortality was significantly higher in men than women [1.8% vs 0.4%, respectively; relative risk (RR) 3.93, 95% Cl 3.30-4.68] and in bilateral versus unilateral procedures (0.5% vs 0.3%; RR 1.6, 95% CI 1.49-1.72), but no differences were noted by the underlying diagnosis of osteoarthritis (OA) versus rheumatoid arthritis (0.4% vs 0.3%; RR 0.77, 95% CI 0.48-1.24). 90-day mortality showed nonsignificant trends favoring women, OA as the underlying diagnosis, and unilateral procedures. Conclusion. Several demographic and surgical factors were associated with higher 30-day mortality rates following knee and hip arthroplasties. More studies are needed to examine the effect of body mass index, comorbidities, and other modifiable factors, in order to identify interventions to lower mortality rates following arthroplasty procedures. (J Rheumatol 2011;38:1507-13; doi:10.3899/jrheum.110280) C1 [Singh, Jasvinder A.; Kundukulam, Joseph] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham Vet Affairs VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham Vet Affairs VA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. [Riddle, Daniel L.] Virginia Commonwealth Univ, Dept Phys Therapy, Richmond, VA USA. [Riddle, Daniel L.] Virginia Commonwealth Univ, Dept Orthoped Surg, Richmond, VA USA. [Strand, Vibeke] Stanford Univ, Sch Med, Div Immunol Rheumatol, Palo Alto, CA 94304 USA. [Tugwell, Peter] Ottawa Hosp, Dept Med, Inst Populat Hlth, Ctr Global Hlth, Ottawa, ON, Canada. RP Singh, JA (reprint author), Univ Alabama, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006; Tugwell, Peter/0000-0001-5062-0556 FU National Institute of Health (NIH) [1 KL2 RR024151-01, T35 HL007473]; Allergan; Takeda; Savient; Wyeth; Amgen; URL Pharmaceuticals; Novartis FX Dr. Singh was supported by National Institute of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research). Dr. Singh has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth, and Amgen; and consultant fees from Savient, URL Pharmaceuticals, and Novartis. J. Kundukulam was supported by NIH Short Term Training Grant T35 HL007473. NR 10 TC 34 Z9 34 U1 1 U2 4 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2011 VL 38 IS 7 BP 1507 EP 1513 DI 10.3899/jrheum.110280 PG 7 WC Rheumatology SC Rheumatology GA 796HE UT WOS:000293041600045 PM 21724724 ER PT J AU Collins, J McCloskey, C Titchner, R Goodpaster, B Hoffman, M Hauser, D Wilson, M Eid, G AF Collins, Joy McCloskey, Carol Titchner, Rebecca Goodpaster, Bret Hoffman, Marcus Hauser, Debra Wilson, Mark Eid, George TI Preoperative weight loss in high-risk superobese bariatric patients: a computed tomography-based analysis SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Article DE Morbid obesity; Gastric bypass; Bariatric surgery; Low-calorie diet; LCD; High risk ID GASTRIC BYPASS-SURGERY; OBESITY; FAT; OUTCOMES; LIVER; DIET AB Background: Superobesity, through organomegaly, excessive adiposity, and associated severe co-morbidities, is a recognized risk factor for bariatric surgery. Our study examined the utility of preoperative weight loss with a liquid low-calorie diet (LCD) as a method of risk reduction. Methods: All patients with a body mass index (BMI) > 50 kg/m(2) were instructed to consume a LCD (800 kcal/d) with the goal of losing >= 10% of their body weight. The co-morbidities were monitored. The abdominal wall depth and cross-sectional areas of subcutaneous adipose tissue (SAT) at 12 and 20 cm below the costal margin, visceral adipose tissue (VAT), and liver volume were measured, using computed tomography, at baseline and after completion of the LCD. Laparoscopic gastric bypass was performed in all patients. Results: The study included 30 patients (27 men and 3 women) with a mean age of 53 years (range 34-53). The mean BMI was reduced from 56 kg/m(2) (range 50-69) at baseline to 49 kg/m(2) (range 43-60) after an average of 9 weeks of the LCD. The VAT decreased from a mean of 388 cm(2) to 342 cm(2). The abdominal wall depth decreased from 3.6 to 3.2 cm at 12 cm below the costal margin and from 3.7 to 3.4 cm at 20 cm. The mean SAT at both 12 and 20 cm below the costal margin had decreased from 577 cm(2) and 687 cm(2) to 509 cm(2) and 614 cm(2), respectively. The liver volume was reduced by 18%. All co-morbidities were well controlled at LCD completion. No patient died, and 2 minor complications occurred postoperatively. Conclusion: The results of our study have shown that preoperative LCD is a safe and effective tool leading to a significant decrease in liver volume and abdominal wall depth, as well as a reduction in both VAT and SAT. Its use might contribute to improved short-term surgical outcomes in high-risk superobese patients. (Surg Obes Relat Dis 2011;7:480-485.) Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery. C1 [McCloskey, Carol; Hoffman, Marcus; Eid, George] Univ Pittsburgh Med Ctr, Div Minimally Invas Surg, Pittsburgh, PA 15213 USA. [Collins, Joy] Childrens Hosp Philadelphia, Div Gen & Thorac Surg, Philadelphia, PA 19104 USA. [Titchner, Rebecca; Hauser, Debra; Wilson, Mark; Eid, George] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Goodpaster, Bret] Univ Pittsburgh, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA USA. RP Eid, G (reprint author), Univ Pittsburgh Med Ctr, Div Minimally Invas Surg, 300 Halket St, Pittsburgh, PA 15213 USA. EM eidgm@upmc.edu NR 17 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD JUL-AUG PY 2011 VL 7 IS 4 BP 480 EP 485 DI 10.1016/j.soard.2010.09.026 PG 6 WC Surgery SC Surgery GA 811HC UT WOS:000294196300007 PM 21185789 ER PT J AU Breitner, JC Baker, LD Montine, TJ Meinert, CL Lyketsos, CG Ashe, KH Brandt, J Craft, S Evans, DE Green, RC Ismail, MS Martin, BK Mullan, MJ Sabbagh, M Tariot, PN AF Breitner, John C. Baker, Laura D. Montine, Thomas J. Meinert, Curtis L. Lyketsos, Constantine G. Ashe, Karen H. Brandt, Jason Craft, Suzanne Evans, Denis E. Green, Robert C. Ismail, M. Saleem Martin, Barbara K. Mullan, Michael J. Sabbagh, Marwan Tariot, Pierre N. CA ADAPT Res Grp TI Extended results of the Alzheimer's disease anti-inflammatory prevention trial SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Randomized controlled trial; Nonsteroidal anti-inflammatory drugs; Follow-up; Biomarkers; Hypothesis ID RANDOMIZED CONTROLLED-TRIAL; MILD COGNITIVE IMPAIRMENT; MINI-MENTAL STATE; SYNAPTIC PLASTICITY; DRUGS; CELECOXIB; NAPROXEN; NSAIDS; RISK; CYCLOOXYGENASE AB Background: Epidemiologic evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) delay onset of Alzheimer's dementia (AD), but randomized trials show no benefit from NSAIDs in patients with symptomatic AD. The Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) randomized 2528 elderly persons to naproxen or celecoxib versus placebo for 2 years (standard deviation = 11 months) before treatments were terminated. During the treatment interval, 32 cases of AD revealed increased rates in both NSAID-assigned groups. Methods: We continued the double-masked ADAPT protocol for 2 additional years to investigate incidence of AD (primary outcome). We then collected cerebrospinal fluid (CSF) from 117 volunteer participants to assess their ratio of CSF tau to A beta(1-42). Results: Including 40 new events observed during follow-up of 2071 randomized individuals (92% of participants at treatment cessation), there were 72 AD cases. Overall, NSAID-related harm was no longer evident, but secondary analyses showed that increased risk remained notable in the first 2.5 years of observations, especially in 54 persons enrolled with cognitive impairment-no dementia (CIND). These same analyses showed later reduction in AD incidence among asymptomatic enrollees who were given naproxen. CSF biomarker assays suggested that the latter result reflected reduced Alzheimer-type neurodegeneration. Conclusions: These data suggest a revision of the original ADAPT hypothesis that NSAIDs reduce AD risk, as follows: NSAIDs have an adverse effect in later stages of AD pathogenesis, whereas asymptomatic individuals treated with conventional NSAIDs such as naproxen experience reduced AD incidence, but only after 2 to 3 years. Thus, treatment effects differ at various stages of disease. This hypothesis is consistent with data from both trials and epidemiological studies. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Breitner, John C.] Douglas Mental Hlth Univ Inst Res Ctr, Ctr Studies Prevent Alzheimers Dis, Montreal, PQ, Canada. [Breitner, John C.] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Breitner, John C.; Baker, Laura D.; Craft, Suzanne] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Baker, Laura D.; Craft, Suzanne] Univ Washington, Med Ctr, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Montine, Thomas J.] Univ Washington, Med Ctr, Dept Pathol, Div Neuropathol, Seattle, WA 98195 USA. [Meinert, Curtis L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Meinert, Curtis L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Lyketsos, Constantine G.; Brandt, Jason] Johns Hopkins Med Inst, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Lyketsos, Constantine G.; Brandt, Jason] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Ashe, Karen H.] Minneapolis VA Med Ctr, Ctr Geriatr Res Educ & Clin, Minneapolis, MN USA. [Ashe, Karen H.] Univ Minnesota, Sch Med, N Bud Grossman Ctr Memory Res & Care, Dept Neurol, Minneapolis, MN 55455 USA. [Ashe, Karen H.] Univ Minnesota, Sch Med, N Bud Grossman Ctr Memory Res & Care, Dept Neurosci, Minneapolis, MN 55455 USA. [Evans, Denis E.] Rush Univ, Med Ctr, Rush Inst Healthy Aging, Chicago, IL 60612 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Genet, Boston, MA 02118 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. [Ismail, M. Saleem] Univ Rochester, Dept Psychiat, Rochester, NY USA. [Martin, Barbara K.] Lancaster Heart & Stroke Fdn, Lancaster, PA USA. [Mullan, Michael J.] Roskamp Inst, Sarasota, FL USA. [Sabbagh, Marwan] Banner Sun Hlth Res Inst, Cleo Roberts Ctr, Sun City, AZ USA. [Tariot, Pierre N.] Banner Alzheimers Inst, Memory Disorders Ctr, Phoenix, AZ USA. RP Breitner, JC (reprint author), Douglas Mental Hlth Univ Inst Res Ctr, Ctr Studies Prevent Alzheimers Dis, Montreal, PQ, Canada. EM john.breitner@mcgill.ca OI Brandt, Jason/0000-0001-7381-6244; Mullan, Michael/0000-0002-1473-7527 FU U.S. Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington by NIH [U01-AG-15477, R01-AG-24010, P50-AG-05136]; N. Bud Grossman Center for Memory Research and Care, Minneapolis, MN; McGill University FX This work was supported by the U.S. Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington, by NIH grants U01-AG-15477, R01-AG-24010, and P50-AG-05136, and by the N. Bud Grossman Center for Memory Research and Care, Minneapolis, MN, and McGill University. Celecoxib and matching placebo were provided by Pfizer, Inc. Naproxen sodium and its placebo were provided by Bayer Consumer Healthcare. No funding or supporting agency had any role in the design or conduct of the study; collection, management, or interpretation of the data; or preparation of the manuscript. Courtesy copies of the manuscript have been provided to the funding agency and to Pfizer, Inc., and Bayer Consumer Heathcare. Data management, descriptive statistics, and primary analyses for ADAPT were provided by the ADAPT Coordinating Center under direction of Drs. Meinert and Martin. The planned and ad hoc secondary analyses, as well as derivation of additional descriptive statistics, were performed by Dr. Baker. Each of these parties verified the analytical results of the others. The authors are deeply indebted to Ms. Jane Anau for her superb technical assistance, to the outstanding staff of the ADAPT field sites and Coordinating Center and, especially, to the ADAPT participant cohort for their persistent commitment and generosity of time and effort. NR 38 TC 147 Z9 153 U1 4 U2 34 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 JUL PY 2011 VL 7 IS 4 BP 402 EP 411 DI 10.1016/j.jalz.2010.12.014 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 802DT UT WOS:000293490200005 PM 21784351 ER PT J AU Johnson, SC La Rue, A Hermann, BP Xu, GF Koscik, RL Jonaitis, EM Bendlin, BB Hogan, KJ Roses, AD Saunders, AM Lutz, MW Asthana, S Green, RC Sager, MA AF Johnson, Sterling C. La Rue, Asenath Hermann, Bruce P. Xu, Guofan Koscik, Rebecca L. Jonaitis, Erin M. Bendlin, Barbara B. Hogan, Kirk J. Roses, Allen D. Saunders, Ann M. Lutz, Michael W. Asthana, Sanjay Green, Robert C. Sager, Mark A. TI The effect of TOMM40 poly-T length on gray matter volume and cognition in middle-aged persons with APOE epsilon 3/epsilon 3 genotype SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Posterior cingulate; Risk factors; Genetics; APOE; TOMM40 ID ONSET ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; FAMILY-HISTORY; PARENTAL HISTORY; HIPPOCAMPAL ATROPHY; QUANTITATIVE TRAIT; E4 ALLELE; MEMORY; ASSOCIATION; IMPAIRMENT AB Objective: Apolipoprotein E (APOE) genotypes are associated with variable risk of developing late-onset Alzheimer's disease (LOAD), with APOE epsilon 4 (APOE epsilon 4) having higher risk. A variable poly-T length polymorphism at rs10524523, within intron 6 of the translocase of the outer mitochondria] membrane (TOMM40) gene, has been shown to influence age of onset in LOAD, with very long (VL) poly-T length associated with earlier disease onset, and short poly-T length associated with later onset. In this study, we tested the hypothesis that brain and cognitive changes suggestive of presymptomatic LOAD may be associated with this TOMM40 polymorphism. Methods: Among healthy APOE epsilon 3 homozygous adults (N = 117; mean age, 55 years), we compared those who were homozygous for VL/VL (n = 35) TOMM40 poly-T lengths (who were presumably at higher risk) with those homozygous for short (S/S; n = 38) poly-T lengths, as well as those with heterozygous (S/VL; n = 44) poly-T length polymorphisms, on measures of learning and memory and on structural brain imaging. Results: The VL/VL group showed lower performance than the S/S TOMM40 group on primacy retrieval from a verbal list learning task, a finding which is also seen in early Alzheimer's disease. A dose-dependent increase in the VL TOMM40 polymorphism (from no VL alleles, to S/VL heterozygous, to VL/VL homozygous) was associated with decreasing gray matter volume in the ventral posterior cingulate and medial ventral precuneus, a region of the brain affected early in LOAD. Conclusions: These findings among APOE epsilon 3/epsilon 3 late middle-aged adults suggest that a subgroup with VL TOMM40 poly-T lengths may be experiencing incipient LOAD-related cognitive and brain changes. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Johnson, Sterling C.; La Rue, Asenath; Hermann, Bruce P.; Koscik, Rebecca L.; Jonaitis, Erin M.; Hogan, Kirk J.; Asthana, Sanjay; Sager, Mark A.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI 53706 USA. [Johnson, Sterling C.; Xu, Guofan; Bendlin, Barbara B.; Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Johnson, Sterling C.; La Rue, Asenath; Hermann, Bruce P.; Xu, Guofan; Bendlin, Barbara B.; Asthana, Sanjay; Sager, Mark A.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Roses, Allen D.; Saunders, Ann M.; Lutz, Michael W.] Duke Univ, Deane Drug Discovery Inst, Durham, NC USA. [Green, Robert C.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Green, Robert C.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. RP Johnson, SC (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI 53706 USA. EM scjohnson@wisc.edu FU NIH [R01 AG027161, R01 AG021155, P50 AG033514]; Alzheimer's Disease Research Center; Clinical and Translational Science Award [UL1RR025011]; Helen Bader Foundation; Northwestern Mutual Foundation; Extendicare Foundation; Veterans Administration; [RC1AG035635-01] FX This study was supported by grants for the NIH: R01 AG027161; R01 AG021155; P50 AG033514 Alzheimer's Disease Research Center; and UL1RR025011 Clinical and Translational Science Award. Dr. Roses and Dr. Lutz are supported in part by RC1AG035635-01. Portions of this research were supported by the Helen Bader Foundation, Northwestern Mutual Foundation, Extendicare Foundation, and from the Veterans Administration including facilities and resources at the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital, Madison, WI. NR 40 TC 40 Z9 40 U1 2 U2 8 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 JUL PY 2011 VL 7 IS 4 BP 456 EP 465 DI 10.1016/j.jalz.2010.11.012 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 802DT UT WOS:000293490200011 PM 21784354 ER PT J AU Wang, C Jackson, G Jones, TH Matsumoto, AM Nehra, A Perelman, MA Swerdloff, RS Traish, A Zitzmann, M Cunningham, G AF Wang, Christina Jackson, Graham Jones, T. Hugh Matsumoto, Alvin M. Nehra, Ajay Perelman, Michael A. Swerdloff, Ronald S. Traish, Abdul Zitzmann, Michael Cunningham, Glenn TI Low Testosterone Associated With Obesity and the Metabolic Syndrome Contributes to Sexual Dysfunction and Cardiovascular Disease Risk in Men With Type 2 Diabetes SO DIABETES CARE LA English DT Review ID HORMONE-BINDING GLOBULIN; LOW SERUM TESTOSTERONE; ANDROGEN DEPRIVATION THERAPY; LOOK-AHEAD TRIAL; MIDDLE-AGED MEN; QUALITY-OF-LIFE; ERECTILE DYSFUNCTION; HYPOGONADAL MEN; DOUBLE-BLIND; INSULIN SENSITIVITY C1 [Wang, Christina; Swerdloff, Ronald S.] Harbor UCLA Med Ctr, Dept Med, Div Endocrinol, Torrance, CA 90509 USA. [Wang, Christina; Swerdloff, Ronald S.] Los Angeles Biomed Res Inst, Torrance, CA USA. [Jackson, Graham] London Bridge Hosp, London, England. [Jones, T. Hugh] Univ Sheffield, Barnsley Hosp, Robert Hague Ctr Diabet & Endocrinol, Sch Med, Sheffield, S Yorkshire, England. [Jones, T. Hugh] Univ Sheffield, Sch Med, Dept Metab, Sheffield, S Yorkshire, England. [Matsumoto, Alvin M.] Univ Washington, Sch Med, Ctr Geriatr Res Educ & Clin, VA Puget Sound Hlth Care Syst,Dept Med, Seattle, WA USA. [Nehra, Ajay] Mayo Clin, Dept Urol, Rochester, MN USA. [Perelman, Michael A.] NY Weill Cornell Coll Med, Dept Psychiat, New York, NY USA. [Perelman, Michael A.] NY Weill Cornell Coll Med, Dept Reprod Med, New York, NY USA. [Perelman, Michael A.] NY Weill Cornell Coll Med, Dept Urol, New York, NY USA. [Traish, Abdul] Boston Univ, Sch Med, Dept Urol, Boston, MA 02118 USA. [Zitzmann, Michael] Univ Clin Muenster, Clin Androl Ctr Reprod Med & Androl, Munster, Germany. [Cunningham, Glenn] Baylor Coll Med, Dept Med, St Lukes Baylor Diabet Program, Houston, TX 77030 USA. [Cunningham, Glenn] Baylor Coll Med, Dept Mol & Cellular Biol, St Lukes Baylor Diabet Program, Houston, TX 77030 USA. RP Wang, C (reprint author), Harbor UCLA Med Ctr, Dept Med, Div Endocrinol, Torrance, CA 90509 USA. EM wang@labiomed.org FU GlaxoSmithKline; Repros Therapeutics; Bayer-Schering Pharma; Lilly; Repros; Clarus Therapeutics; Abbott (Solvay) FX C.W. received research support from GlaxoSmithKline and Repros Therapeutics, received research materials from Besins Health Care, and is a consultant to GlaxoSmithKline and Lilly. T.H.J. is a consultant for Prostrakan and Bayer-Schering Pharma and has received research support and lecture honorarium from Bayer-Schering Pharma. R.S.S. is a consultant for Abbott (Solvay), Clams Therapeutics, Endo Pharmaceuticals, GlaxoSmithKline, Lilly, and Repros Therapeutics and has received research support from Lilly, Repros, and Clarus Therapeutics. G.C. is a consultant for Abbott (Solvay), Endo (Indevus), and GlaxoSmithKline; has received research support from Abbott (Solvay) and Repros Therapeutics; and is on the speakers' list for Abbott (Solvay). No other potential conflicts of interest relevant to this article were reported. NR 60 TC 87 Z9 93 U1 0 U2 9 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 JUL PY 2011 VL 34 IS 7 BP 1669 EP 1675 DI 10.2337/dc10-2339 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 799CN UT WOS:000293261200043 PM 21709300 ER PT J AU Kahn, SE Utzschneider, KM AF Kahn, Steven E. Utzschneider, Kristina M. TI What's Next for Diabetes Prevention? SO DIABETES CARE LA English DT Editorial Material ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; BETA-CELL DYSFUNCTION; ROSIGLITAZONE; METFORMIN; TRIAL; MELLITUS; COMPLICATIONS; REDUCTION C1 [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. EM skahn@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU NIDDK NIH HHS [P30 DK017047] NR 19 TC 2 Z9 2 U1 0 U2 1 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 JUL PY 2011 VL 34 IS 7 BP 1678 EP 1680 DI 10.2337/dc11-0694 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 799CN UT WOS:000293261200045 PM 21709302 ER PT J AU Blank, RD AF Blank, Robert D. CA FRAX Position Dev Conf Members TI Official Positions for FRAX (R) Clinical Regarding Prior Fractures SO JOURNAL OF CLINICAL DENSITOMETRY LA English DT Article DE FRAX; past fractures; fracture risk; vertebral morphometry; family history ID EUROPEAN PROSPECTIVE OSTEOPOROSIS; PREVALENT VERTEBRAL FRACTURES; HIP FRACTURE; SUBSEQUENT FRACTURE; BONE-DENSITY; COLLES FRACTURE; LIMB FRACTURES; FAMILY-HISTORY; SPINE FRACTURE; DISTAL FOREARM AB The 2010 Position Development Conference addressed four questions related to the impact of previous fractures on 10-year fracture risk as calculated by FRAX (R). Does the number of past fractures affect future fracture risk? Does the severity of past vertebral fractures affect future fracture risk? Does the site of past fractures affect future fracture risk? Should the family history of fracture be expanded to include additional sites, additional family members, or account for age at fracture? To address these questions, PubMed was searched on the keywords "fracture, epidemiology, osteoporosis." Titles of retrieved articles were reviewed for an indication that risk for future fracture was discussed. Abstracts of these articles were reviewed for an indication that one or more of the questions listed above was discussed. For those that did, the articles were reviewed in greater detail to extract the findings and to find additional past work and citing works that also bore on the questions. The official positions and the supporting literature review are presented here. FRAX (R) underestimates fracture probability in persons with a history of multiple fractures (good, A, W). FRAX (R) may underestimate fracture probability in individuals with prevalent severe vertebral fractures (good, A, W). While there is evidence that hip, vertebral, and humeral fractures appear to confer greater risk of subsequent fracture than fractures at other sites, quantification of this incremental risk in FRAX (R) is not possible (fair, B, W). FRAX (R) may underestimate fracture probability in individuals with a parental history of non-hip fragility fracture (fair, B, W). Limitations of the methodology include performance by a single reviewer, preliminary review of the literature being confined to titles, and secondary review being limited to abstracts. Limitations of the evidence base include publication bias, overrepresentation of persons of European descent in the published studies, and technical differences in the methods used to identify prevalent and incident fractures. Emerging topics for future research include fracture epidemiology in non-European populations and men, the impact of fractures in family members other than parents, and the genetic contribution to fracture risk. C1 [Blank, Robert D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Endocrinol, Madison, WI 53705 USA. [Blank, Robert D.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Blank, RD (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Endocrinol, 4142 MFCB,5148,1685 Highland Ave, Madison, WI 53705 USA. EM rdb@medicine.wisc.edu RI Moayyeri, Alireza/N-3332-2014; Stepan, Jan /A-7280-2013 OI Moayyeri, Alireza/0000-0002-9143-2161; Stepan, Jan /0000-0003-1541-8306 FU Office of Research and Development, Biomedical Laboratory R&D Service, Department of Veterans Affairs; National Institutes of Health [R01-AR54753] FX This report is Madison GRECC manuscript 2010-22. RDB gratefully acknowledges research support from the Office of Research and Development, Biomedical Laboratory R&D Service, Department of Veterans Affairs and from the National Institutes of Health R01-AR54753. NR 40 TC 11 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1094-6950 J9 J CLIN DENSITOM JI J. Clin. Densitom. PD JUL-SEP PY 2011 VL 14 IS 3 BP 205 EP 211 DI 10.1016/j.jocd.2011.05.009 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 808PC UT WOS:000293989900006 PM 21810526 ER PT J AU Widera, EW Rosenfeld, KE Fromme, EK Sulmasy, DP Arnold, RM AF Widera, Eric W. Rosenfeld, Kenneth E. Fromme, Erik K. Sulmasy, Daniel P. Arnold, Robert M. TI Approaching Patients and Family Members Who Hope for a Miracle SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Miracles; divine intervention; religious beliefs; decision making; spiritual support; pastoral care ID TREATMENT PREFERENCES; ADVANCED CANCER; NEAR-DEATH; LIFE; PHYSICIANS; BELIEFS; CARE; FUTILITY; END; ICU AB A clinical problem may arise when caring for patients or their surrogates who prefer continued aggressive care based on the belief that a miracle will occur, despite a clinician's belief that further medical treatment is unlikely to have any meaningful benefit. An evidence-based approach is provided for the clinician by breaking this complex clinical problem into a series of more focused clinical questions and subsequently answering them through a critical appraisal of the existing medical literature. Belief in miracles is found to be common in the United States and is an important determinant of how decisions are made for those with advanced illness. There is a growing amount of evidence that suggests end-of-life outcomes improve with the provision of spiritual support from medical teams, as well as with a proactive approach to medical decision making that values statements given by patients and family members. J Pain Symptom Manage 2011; 42: 119-125. Published by Elsevier Inc. on behalf of the U.S. Cancer Pain Relief Committee. C1 [Widera, Eric W.] Dept Vet Affairs Med Ctr, San Francisco, CA USA. [Widera, Eric W.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Rosenfeld, Kenneth E.] Vet Adm Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Sect Palliat Care, Los Angeles, CA USA. [Fromme, Erik K.] Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97201 USA. [Sulmasy, Daniel P.] Univ Chicago, Dept Med, MacLean Ctr Clin Med Eth, Chicago, IL 60637 USA. [Sulmasy, Daniel P.] Univ Chicago, Divin Sch, Chicago, IL 60637 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 Widera, EW (reprint author), VA Med Ctr 181G, 4150 Clement St, San Francisco, CA 94121 USA. EM eric.widera@ucsf.edu FU Hartford Foundation FX Dr. Widera is supported by the Hartford Foundation as a Center of Excellence Faculty Scholar. The authors of this manuscript have no conflicts to disclose. NR 21 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUL PY 2011 VL 42 IS 1 BP 119 EP 125 DI 10.1016/j.jpainsymman.2011.03.008 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 802MO UT WOS:000293515900012 PM 21641763 ER PT J AU Teitelman, AM Tennille, J Bohinski, JM Jemmott, LS Jemmott, JB AF Teitelman, Anne M. Tennille, Julie Bohinski, Julia M. Jemmott, Loretta S. Jemmott, John B., III TI Unwanted Unprotected Sex Condom Coercion by Male Partners and Self-silencing of Condom Negotiation Among Adolescent Girls SO ADVANCES IN NURSING SCIENCE LA English DT Article DE adolescent; coercion; female; HIV; prevention; sexual behavior ID DATING VIOLENCE; REJECTION SENSITIVITY; AFRICAN-AMERICAN; RISK BEHAVIOR; INTERVENTIONS; PREGNANCY; FEMALES; POWER; COMMUNICATION; HEALTH AB This exploratory study used the theory of reasoned action and the theory of gender and power to guide elicitation of partner-related impediments to condom use among 64 adolescent girls living in poor urban areas with high rates of HIV and partner abuse. About 53% indicated that they had experienced unwanted, unprotected vaginal sex and 25% indicated that they were unable to discuss condom use with a partner. Novel qualitative findings related to condom coercion, condom sabotage, and self-silencing of condom negotiation are discussed in the context of connecting partner abuse to interpersonal control over condom use. Implications for intervention design are discussed. C1 [Teitelman, Anne M.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. [Tennille, Julie] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Jemmott, John B., III] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Jemmott, John B., III] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA. RP Teitelman, AM (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Fagin Hall 2L,Room 244,418 Curie Blvd, Philadelphia, PA 19104 USA. EM teitelm@nursing.upenn.edu FU NIMH [1K01MII080649-01A1]; University of Pennsylvania: Center for AIDS Research; Institute for Urban Research FX This research was supported by NIMH grant 1K01MII080649-01A1 and University of Pennsylvania: Center for AIDS Research and Institute for Urban Research. The authors thank late Dr Martin Fishbein for suggestions about the wording of the open-ended questions on the brief survey; Dr Patricia Benner, Dr Pat D'Antonio, and Annet Davis-Vogel for reading and commenting on drafts of the article; Lynette Gueits for her role in advising on the development of the focus group guide; the Talking about Relationships Project research team members for logistical support during focus groups and for insightful discussions during the coding process; and the research study participants for the time and thoughtful comments. NR 49 TC 33 Z9 33 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0161-9268 EI 1550-5014 J9 ADV NURS SCI JI Adv. Nurs. Sci. PD JUL-SEP PY 2011 VL 34 IS 3 BP 243 EP 259 DI 10.1097/ANS.0b013e31822723a3 PG 17 WC Nursing SC Nursing GA 803PM UT WOS:000293593200009 PM 21822072 ER PT J AU Welch, LK Olson, KL Snow, KE Pointer, L Lambert-Kerzner, A Havranek, EP Magid, DJ Ho, PM AF Welch, Lesley K. Olson, Kari L. Snow, Karen E. Pointer, Lauren Lambert-Kerzner, Anne Havranek, Edward P. Magid, David J. Ho, P. Michael TI Systolic Blood Pressure Control After Participation in a Hypertension Intervention Study SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID OUTCOMES; DISEASE AB Objective: To evaluate whether systolic blood pressure (SBP) control is maintained following participation in a multimodal hypertension intervention. Study Design: This was a retrospective cohort of patients completing the Improving Blood Pressure in Colorado study, a randomized trial comparing a multimodal intervention with usual care for patients who had uncontrolled hypertension. Methods: Chart review assessed the first SBP measurement recorded as part of routine care after the study ended. Among patients who had controlled SBP at the final study visit, the proportions who had uncontrolled SBP during follow-up were compared for the intervention and usual care (UC) groups. Kaplan-Meier estimates assessed time to uncontrolled SBP by treatment arm. Results: Of 283 patients completing the Improving Blood Pressure in Colorado study, 51.5% in the intervention and 46.9% in the UC group had controlled SBP at the final study visit. Of patients with controlled SBP, 37.0% and 46.4% of patients in the intervention and UC groups, respectively, had uncontrolled SBP at their initial measurement during follow-up (P = .32). There was no difference in median time to uncontrolled SBP (126 vs 114 days for the intervention and UC groups, respectively; P = .47). Conclusions: SBP control was not maintained in a significant proportion of patients in both groups following hypertension study participation. These findings suggest the need for interventions to focus on longer-term BP control in contrast to the short duration of most hypertension intervention trials. (Am J Manag Care. 2011; 17(7):473-478) C1 [Welch, Lesley K.; Pointer, Lauren; Lambert-Kerzner, Anne; Ho, P. Michael] Denver VA Med Ctr, Denver, CO USA. [Olson, Kari L.] Kaiser Permanente Colorado, Dept Pharm, Aurora, CO USA. [Olson, Kari L.; Lambert-Kerzner, Anne; Havranek, Edward P.; Magid, David J.; Ho, P. Michael] Univ Colorado Denver, Denver, CO USA. [Snow, Karen E.; Havranek, Edward P.] Denver Hlth Med Ctr, Denver, CO USA. [Magid, David J.] Kaiser Permanente Colorado, Inst Hlth, Denver, CO USA. RP Welch, LK (reprint author), 1055 Clermont St, Denver, CO 80220 USA. EM Lesley.welch@va.gov FU American Heart Association [0535086N]; VA Health Services Research and Development Award [05-026] FX This work was funded by an award from the American Heart Association (0535086N).; Dr Ho is supported by a VA Health Services Research and Development Award (05-026) and serves as a consultant for Wellpoint, Inc. He also reports having given lectures for Pfizer in Japan. The authors (LKW, KLO, KES, LP, AL-K, EPH, DJM) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article. NR 13 TC 4 Z9 4 U1 0 U2 0 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUL PY 2011 VL 17 IS 7 BP 473 EP 478 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 801QJ UT WOS:000293455000007 PM 21819167 ER PT J AU Zhao, KQ Goldstein, N Yang, HB Cowan, AT Chen, B Zheng, CQ Palmer, JN Kreindler, JL Cohen, NA AF Zhao, Ke-Qing Goldstein, Natalia Yang, Haibin Cowan, Andrew T. Chen, Bei Zheng, Chunquan Palmer, James N. Kreindler, James L. Cohen, Noam A. TI Inherent differences in nasal and tracheal ciliary function in response to Pseudomonas aeruginosa challenge SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID LIQUID INTERFACE CULTURES; BEAT FREQUENCY; CHRONIC RHINOSINUSITIS; IN-VITRO; AIRWAY; EPITHELIUM; PYOCYANIN; SINUSITIS; TRANSPORT; RHINITIS AB Background: Sinonasal mucosal biofilms are recognized as contributors to the pathogenesis of chronic rhinosinusitis (CRS). Attachment of bacteria to the sinonasal surface is an initial step in biofilm formation. A critical defense against this occurrence is mucociliary clearance (MCC). To ascertain whether the ciliary component of MCC is uniform throughout the airway we compared ciliary beat frequency (CBF) in the murine nasal septum and trachea at baseline and after challenge with Pseudomonas aeruginosa, a common pathogen of CRS. Methods: Murine septal and tracheal air-liquid interface cultures were evaluated for basal and stimulated CBF after exposure to control or conditioned media from Pseudomonas. Additionally, the attachment of Pseudomonas to nasal and tracheal cultures was assessed after pretreatment with control or conditioned media. Results: Basal CBF is significantly slower in primary nasal airway cultures compared with tracheal airway cultures. Tracheal airway cultures show resistance to Pseudomonas secreted ciliotoxins not evident in nasal septal cultures. Furthermore, after challenge with viable Pseudomonas, significantly more bacteria attach to the nasal cultures compared with the tracheal cultures. Conclusion: Using primary murine nasal and tracheal airway cultures we show inherent differences in cilia function and increased susceptibility of the upper airway to attachment by Pseudomonas. Understanding the differences between upper and subglottic airway mucociliary clearance should lead to novel approaches in the management of upper airway infection. (Am J Rhinol Allergy 25, 209-213, 2011; doi: 10.2500/ajra.2011.25.3614) C1 [Zhao, Ke-Qing; Goldstein, Natalia; Chen, Bei; Palmer, James N.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19004 USA. [Zhao, Ke-Qing; Zheng, Chunquan] Fudan Univ, Sch Shanghai Med, Eye & Ear Nose & Throat Hosp, Dept Otorhinolaryngol Head & Neck Surg, Shanghai 200433, Peoples R China. [Goldstein, Natalia] Pontificia Univ Catolica Chile, PhD Program Med Sci, Santiago, Chile. [Yang, Haibin] Xiamen Univ, Zhongshan Hosp, Dept Otolaryngol, Xiamen, Fujian, Peoples R China. [Cowan, Andrew T.] Temple Univ, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19122 USA. [Kreindler, James L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Kreindler, James L.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19004 USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. RP Cohen, NA (reprint author), Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Ravdin Bldg,5th Floor,3400 Spruce St, Philadelphia, PA 19004 USA. EM cohenn@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932 NR 32 TC 12 Z9 12 U1 0 U2 10 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 JUL-AUG PY 2011 VL 25 IS 4 BP 209 EP 213 DI 10.2500/ajra.2011.25.3614 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 797OB UT WOS:000293136100012 PM 21819755 ER PT J AU Hwang, U Aufses, AH Bickell, NA AF Hwang, Ula Aufses, Arthur H., Jr. Bickell, Nina A. TI Factors associated with delays to emergency care for bowel obstruction SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Emergency department; Bowel obstruction; Hand-offs; Delays ID CLOSED MALPRACTICE CLAIMS; NURSE-STAFFING LEVELS; QUALITY; TIME; MANAGEMENT; RISK; PAIN; APPENDICITIS; DIAGNOSES; OUTCOMES AB BACKGROUND: Our objective was to determine factors associated with delays to first treatment for emergency department (ED) patients diagnosed with small-bowel obstruction (SBO). METHODS: This was a retrospective study of ED patients with SBO. Data were collected from medical records, administrative databases, and staffing schedules at an urban, tertiary care medical center from June 1, 2001, to November 30, 2002. Patient-related characteristics and processes of ED and hospital care were evaluated. Outcomes studied were time to first treatment (nasogastric tube or surgery) and risk of surgical resection. RESULTS: A total of 193 patients were diagnosed with confirmed intestinal obstruction. Patients with longer times to first treatment arrived during ED clinician hand-offs (adjusted hazard ratio, .40; 95% confidence interval, .17-.98). Patients with longer times to surgery consult (ref. first quartile) had greater odds of surgical resection (second quartile adjusted odds ratio, 6.91; 95% confidence interval, 1.85-24.80). CONCLUSIONS: Remediable ED and hospital factors were associated with longer times to treatment for patients with bowel obstruction. Published by Elsevier Inc. C1 [Hwang, Ula] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Hwang, Ula] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Care, New York, NY 10029 USA. [Hwang, Ula] Mt Sinai Sch Med, Dept Hlth Evidence & Policy, New York, NY 10029 USA. [Aufses, Arthur H., Jr.; Bickell, Nina A.] Mt Sinai Sch Med, Dept Surg, New York, NY 10029 USA. [Aufses, Arthur H., Jr.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Bickell, Nina A.] James J Peters Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. RP Hwang, U (reprint author), Mt Sinai Sch Med, Dept Emergency Med, 1 Gustave L Levy Pl,Box 1620, New York, NY 10029 USA. EM ula.hwang@mountsinai.org FU Healthcare Research and Quality [R0313464] FX This study was funded by the Agency for Healthcare Research and Quality R0313464 (N.A.B.). NR 29 TC 4 Z9 4 U1 1 U2 3 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 JUL PY 2011 VL 202 IS 1 BP 1 EP 7 DI 10.1016/j.amjsurg.2010.05.003 PG 7 WC Surgery SC Surgery GA 803PR UT WOS:000293593700004 PM 21632032 ER PT J AU Shih, YYI De La Garza, BH Muir, ER Rogers, WE Harrison, JM Kiel, JW Duong, TQ AF Shih, Yen-Yu I. De La Garza, Bryan H. Muir, Eric R. Rogers, William E. Harrison, Joseph M. Kiel, Jeffrey W. Duong, Timothy Q. TI Lamina-Specific Functional MRI of Retinal and Choroidal Responses to Visual Stimuli SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CEREBRAL-BLOOD-FLOW; DIFFUSE LUMINANCE FLICKER; LASER-DOPPLER FLOWMETRY; BOLD FMRI; OPTIC-NERVE; SOMATOSENSORY STIMULATION; HEMODYNAMIC-RESPONSE; FOREPAW STIMULATION; ANESTHETIZED RATS; OXYGEN-TENSION AB PURPOSE. To demonstrate lamina-specific functional magnetic resonance imaging (MRI) of retinal and choroidal responses to visual stimulation of graded luminance, wavelength, and frequency. MATERIALS AND METHODS. High-resolution (60 X 60 mu m) MRI was achieved using the blood-pool contrast agent, monocrystalline iron oxide nanoparticles (MION) and a high-magnetic-field (11.7 T) scanner to image functional changes in the normal rat retina associated with various visual stimulations. MION functional MRI measured stimulus-evoked blood-volume (BV) changes. Graded luminance, wavelength, and frequency were investigated. Stimulus-evoked fMRI signal changes from the retinal and choroidal vascular layers were analyzed. RESULTS. MRI revealed two distinct laminar signals that corresponded to the retinal and choroidal vascular layers bounding the retina and were separated by the avascular layer in between. The baseline outer layer BV index was 2-4 times greater than the inner layer BV, consistent with higher choroidal vascular density. During visual stimulation, BV responses to flickering light of different luminance, frequency, and wavelength in the inner layer were greater than those in the outer layer. The inner layer responses were dependent on luminance, frequency, and wavelength, whereas the outer layer responses were not, suggesting differential neurovascular coupling between the two vasculatures. CONCLUSIONS. This is the first report of simultaneous resolution of layer-specific functional responses of the retinal and choroid vascular layers to visual stimulation in the retina. This imaging approach could have applications in early detection and longitudinal monitoring of retinal diseases where retinal and choroidal hemodynamics may be differentially perturbed at various stages of the diseases. (Invest Ophthalmol Vis Sci. 2011; 52:5303-5310) DOI: 10.1167/iovs.10-6438 C1 [Shih, Yen-Yu I.; De La Garza, Bryan H.; Muir, Eric R.; Rogers, William E.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Harrison, Joseph M.; Kiel, Jeffrey W.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008; Muir, Eric/H-8830-2013 OI Shih, Yen-Yu Ian/0000-0001-6529-911X FU NIH/NEI [R01 EY014211, EY018855, R01EY09702]; Department of Veterans Affairs; San Antonio Life Science Institute; American Heart Association [10POST4290091]; San Antonio Area Foundation FX Supported in part by the NIH/NEI (R01 EY014211, EY018855, and R01EY09702), MERIT Award from the Department of Veterans Affairs, and a grant from the San Antonio Life Science Institute to TQD. Y.-Y.I.S. is supported by American Heart Association (10POST4290091) and San Antonio Area Foundation. NR 64 TC 22 Z9 23 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 JUL PY 2011 VL 52 IS 8 BP 5303 EP 5310 DI 10.1167/iovs.10-6438 PG 8 WC Ophthalmology SC Ophthalmology GA 800QC UT WOS:000293377400039 PM 21447679 ER PT J AU Morales, SA Telander, D Notterpek, L Wadehra, M Braun, J Gordon, LK AF Morales, Shawn A. Telander, David Notterpek, Lucia Wadehra, Madhuri Braun, Jonathan Gordon, Lynn K. TI Rewiring Integrin-Mediated Signaling and Cellular Response with the Peripheral Myelin Protein 22 and Epithelial Membrane Protein 2 Components of the Tetraspan Web SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID COLLAGEN GEL CONTRACTION; SURFACE EXPRESSION; IN-VITRO; CELLS; ADHESION; EMP2; FIBROBLASTS; ACTIVATION; COMPLEX; GENE AB PURPOSE. Integrin-mediated collagen gel contraction by ARPE-19 is an in vitro model for proliferative vitreoretinopathy (PVR), an aberrant wound healing response after retinal detachment or ocular trauma. Expression of the tetraspan protein epithelial membrane protein 2 (EMP2) controls gel contraction through FAK activation. Peripheral myelin protein 22 (PMP22), another member of the tetraspan web, is closely related to EMP2. The purpose of this study was to determine whether PMP22 also controls the contractile phase associated with PVR. METHODS. Integrin expression, adhesion, and protein expression were assessed, respectively, through flow cytometry, binding to collagen types I and IV, and Western blot analysis. Collagen gel contraction was assessed using an in vitro assay. RESULTS. Overexpression of PMP22 in ARPE-19 cells (ARPE-19/PMP22) resulted in increased collagen adhesion. Gel contraction, however, was reduced by greater than 50% in ARPE-19/PMP22 cells (P < 0.001). In contrast to the FAK activation observed by increasing EMP2 expression, PMP22 overexpression led to increased AKT activation. The decrease in gel contraction by the ARPE-19/PMP22 cells was partially reversed through either PMP22 siRNA or by blockade of AKT. CONCLUSIONS. Relative expression of EMP2 or PMP22 within the tetraspan web drives a cellular response toward a FAK-or AKT-dependent pathway, respectively. EMP2 and PMP22 differentially regulate collagen gel contraction in the ARPE-19 cell line. The implication of this finding adds a new dimension to the concept of the tetraspan web, in which the abundance of individual tetraspan family members differentially regulates signal transduction and the downstream cellular response. (Invest Ophthalmol Vis Sci. 2011; 52: 5465-5472) DOI: 10.1167/iovs.10-6139 C1 [Gordon, Lynn K.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Wadehra, Madhuri; Braun, Jonathan] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Telander, David] Univ Calif Davis, Dept Ophthalmol & Vis Sci, Davis, CA 95616 USA. [Notterpek, Lucia] Univ Florida, Dept Neurosci, Sch Med, Gainesville, FL 32610 USA. [Gordon, Lynn K.] Greater Los Angeles VA Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP Gordon, LK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM lgordon@ucla.edu OI Braun, Jonathan/0000-0003-1646-2974 FU National Institutes of Health [RO1 EY019909, HD48540]; American Health Assistance Foundation; A. P. Giannini Foundation; Ruzic Foundation FX Supported by National Institutes of Health Grants RO1 EY019909 (LKG, DT) and HD48540 (JB), the American Health Assistance Foundation (LKG), the A. P. Giannini Foundation (SAM), and the Ruzic Foundation (JB). NR 44 TC 1 Z9 1 U1 0 U2 2 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 JUL PY 2011 VL 52 IS 8 BP 5465 EP 5472 DI 10.1167/iovs.10-6139 PG 8 WC Ophthalmology SC Ophthalmology GA 800QC UT WOS:000293377400059 PM 21421883 ER PT J AU Clark, CM Olender, L Cardoni, C Kenski, D AF Clark, Cynthia M. Olender, Lynda Cardoni, Cari Kenski, Diane TI Fostering Civility in Nursing Education and Practice Nurse Leader Perspectives SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material ID INCIVILITY; WORKPLACE; STRATEGIES; FACULTY; STAFF C1 [Clark, Cynthia M.; Cardoni, Cari; Kenski, Diane] Boise State Univ, Sch Nursing, Boise, ID 83725 USA. [Olender, Lynda] Seton Hall Univ, S Orange, NJ 07079 USA. [Olender, Lynda] James J Peters VA Med Ctr, Bronx, NY USA. RP Clark, CM (reprint author), Boise State Univ, Sch Nursing, 1910 Univ Dr, Boise, ID 83725 USA. EM cclark@boisestate.edu NR 29 TC 13 Z9 13 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD JUL-AUG PY 2011 VL 41 IS 7-8 BP 324 EP 330 DI 10.1097/NNA.0b013e31822509c4 PG 7 WC Nursing SC Nursing GA 799EC UT WOS:000293265400008 PM 21799364 ER PT J AU Rosado-Rivera, D Radulovic, M Handrakis, JP Cirnigliaro, CM Jensen, AM Kirshblum, S Bauman, WA Wecht, JM AF Rosado-Rivera, Dwindally Radulovic, M. Handrakis, John P. Cirnigliaro, Christopher M. Jensen, A. Marley Kirshblum, Steve Bauman, William A. Wecht, Jill Maria TI Comparison of 24-hour cardiovascular and autonomic function in paraplegia, tetraplegia, and control groups: Implications for cardiovascular risk SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Paraplegia; Tetraplegia; Autonomic nervous system; Heart rate; Blood pressure; Heart rate variability; Diumal variation; Spinal cord injuries; Cardiovascular risk ID SPINAL-CORD-INJURY; HEART-RATE-VARIABILITY; LOW BLOOD-PRESSURE; CONTINGENT NEGATIVE-VARIATION; SYMPATHETIC-NERVOUS-SYSTEM; VOLUNTARY STATIC EXERCISE; ARTERIAL STIFFNESS; DISEASE RISK; COGNITIVE PERFORMANCE; NON-DIPPERS AB Background: Fluctuations in 24-hour cardiovascular hemodynamics, specifically heart rate (HR) and blood pressure (BP), are thought to reflect autonomic nervous system (ANS) activity. Persons with spinal cord injury (SCI) represent a model of ANS dysfunction, which may affect 24-hour hemodynamics and predispose these individuals to increased cardiovascular disease risk. Objective: To determine 24-hour cardiovascular and ANS function among individuals with tetraplegia (n = 20; TETRA: C4-C8), high paraplegia (n = 10; HP: T2-T5), low paraplegia (n = 9; LP: T7-T12), and non-SCI controls (n = 10). Twenty-four-hour ANS function was assessed by time domain parameters of heart rate variability (HRV); the standard deviation of the 5-minute average R-R intervals (SDANN; milliseconds/ms), and the root-mean square of the standard deviation of the R-R intervals (rMSSD; ms). Subjects wore 24-hour ambulatory monitors to record HR, HRV, and BP. Mixed analysis of variance (ANOVA) revealed significantly lower 24-hour BP in the tetraplegic group; however, BP did not differ between the HP, LP, and control groups. Mixed ANOVA suggested significantly elevated 24-hour HR in the HP and LP groups compared to the TETRA and control groups (P < 0.05); daytime HR was higher in both paraplegic groups compared to the TETRA and control groups (P < 0.01) and nighttime HR was significantly elevated in the LP group compared to the TETRA and control groups (P < 0.01). Twenty-four-hour SDANN was significantly increased in the HP group compared to the LP and TETRA groups (P < 0.05) and rMSSD was significantly lower in the LP compared to the other three groups (P < 0.05). Elevated 24-hour HR in persons with paraplegia, in concert with altered HRV dynamics, may impart significant adverse cardiovascular consequences, which are currently unappreciated. C1 [Rosado-Rivera, Dwindally; Radulovic, M.; Handrakis, John P.; Cirnigliaro, Christopher M.; Jensen, A. Marley; Bauman, William A.; Wecht, Jill Maria] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Rosado-Rivera, Dwindally; Radulovic, M.; Handrakis, John P.; Cirnigliaro, Christopher M.; Jensen, A. Marley; Bauman, William A.; Wecht, Jill Maria] Ctr Excellence, New York, NY USA. [Radulovic, M.; Handrakis, John P.; Cirnigliaro, Christopher M.; Jensen, A. Marley; Bauman, William A.; Wecht, Jill Maria] Med Serv, New York, NY USA. [Radulovic, M.; Handrakis, John P.; Cirnigliaro, Christopher M.; Jensen, A. Marley; Bauman, William A.; Wecht, Jill Maria] Mt Sinai Sch Med, New York, NY USA. [Radulovic, M.; Handrakis, John P.; Cirnigliaro, Christopher M.; Jensen, A. Marley; Bauman, William A.; Wecht, Jill Maria] Dept Med, W Orange, NJ USA. [Radulovic, M.; Handrakis, John P.; Cirnigliaro, Christopher M.; Jensen, A. Marley; Bauman, William A.; Wecht, Jill Maria] Dept Rehabil Med, W Orange, NJ USA. [Handrakis, John P.; Cirnigliaro, Christopher M.; Jensen, A. Marley; Kirshblum, Steve] Kessler Inst Rehabil, W Orange, NJ USA. [Handrakis, John P.] NYIT Sch Hlth Profess, Old Westbury, NY USA. RP Wecht, JM (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM jm.wecht@va.gov FU Veterans Affairs Rehabilitation Research and Development Service [A6161W, B3203R, B4162C] FX We thank Dr Joseph Weir for his support with the statistical analyses. This research was supported by the Veterans Affairs Rehabilitation Research and Development Service (grant no. A6161W, B3203R and B4162C). NR 64 TC 24 Z9 25 U1 1 U2 5 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JUL PY 2011 VL 34 IS 4 BP 395 EP 403 DI 10.1179/2045772311Y.0000000019 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 804BS UT WOS:000293629500007 PM 21903013 ER PT J AU Hoffman, J Salzman, C Garbaccio, C Burns, SP Crane, D Bombardier, C AF Hoffman, Jeanne Salzman, Cynthia Garbaccio, Chris Burns, Stephen P. Crane, Deborah Bombardier, Charles TI Use of on-demand video to provide patient education on spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Patient education; Spinal cord injuries; Media; Print; Digital; Video; Internet; Secondary complications; Prevention; Self-care; Quality of life ID INTERNET USE; HEALTH; PEOPLE AB Background/objective: Persons with chronic spinal cord injury (SCI) have a high lifetime need for ongoing patient education to reduce the risk of serious and costly medical conditions. We have addressed this need through monthly in-person public education programs called SCI Forums. More recently, we began videotaping these programs for streaming on our website to reach a geographically diverse audience of patients, caregivers, and providers. Design/methods: We compared information from the in-person forums to that of the same forums shown streaming on our website during a 1-year period. Results: Both the in-person and Internet versions of the forums received high overall ratings from individuals who completed evaluation forms. Eighty-eight percent of online evaluators and 96% of in-person evaluators reported that they gained new information from the forum; 52 and 64% said they changed their attitude, and 61 and 68% said they would probably change their behavior or take some kind of action based on information they learned. Ninety-one percent of online evaluators reported that video is better than text for presenting this kind of information. Conclusion: Online video is an accessible, effective, and well-accepted way to present ongoing SCI education and can reach a wider geographical audience than in-person presentations. C1 [Hoffman, Jeanne; Salzman, Cynthia; Garbaccio, Chris; Burns, Stephen P.; Crane, Deborah; Bombardier, Charles] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Burns, Stephen P.] VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA USA. RP Hoffman, J (reprint author), Univ Washington, Dept Rehabil, Box 356490, Seattle, WA 98195 USA. EM jeanneh@uw.edu FU Department of Education, National Institute on Disability and Rehabilitation Research, SCI Model Systems at the University of Washington [H133N060033] FX This study was funded by the Department of Education, National Institute on Disability and Rehabilitation Research, SCI Model Systems at the University of Washington H133N060033. NR 15 TC 8 Z9 8 U1 0 U2 1 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JUL PY 2011 VL 34 IS 4 BP 404 EP 409 DI 10.1179/2045772311Y.0000000015 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 804BS UT WOS:000293629500008 PM 21903014 ER PT J AU Lo Re, V Lim, JK Goetz, MB Tate, J Bathulapalli, H Klein, MB Rimland, D Rodriguez-Barradas, MC Butt, AA Gibert, CL Brown, ST Kidwai, F Brandt, C Dorey-Stein, Z Reddy, KR Justice, AC AF Lo Re, Vincent, III Lim, Joseph K. Goetz, Matthew Bidwell Tate, Janet Bathulapalli, Harini Klein, Marina B. Rimland, David Rodriguez-Barradas, Maria C. Butt, Adeel A. Gibert, Cynthia L. Brown, Sheldon T. Kidwai, Farah Brandt, Cynthia Dorey-Stein, Zachariah Reddy, K. Rajender Justice, Amy C. TI Validity of diagnostic codes and liver-related laboratory abnormalities to identify hepatic decompensation events in the Veterans Aging Cohort Study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE hepatic decompensation; end-stage liver disease; epidemiologic methods; outcomes; validation studies ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATOCELLULAR-CARCINOMA; C-VIRUS; DRUG-USERS; FIBROSIS PROGRESSION; COINFECTED PATIENTS; NATURAL-HISTORY; HIV-INFECTION; CIRRHOSIS; MANAGEMENT AB Purpose The absence of validated methods to identify hepatic decompensation in cohort studies has prevented a full understanding of the natural history of chronic liver diseases and impact of medications on this outcome. We determined the ability of diagnostic codes and liver-related laboratory abnormalities to identify hepatic decompensation events within the Veterans Aging Cohort Study (VACS). Methods Medical records of patients with hepatic decompensation codes and/or laboratory abnormalities of liver dysfunction (total bilirubin >= 5.0 g/dL, albumin <= 2.0 g/dL, INR >= 1.7) recorded 1 year before through 6 months after VACS entry were reviewed to identify decompensation events (i.e., ascites, spontaneous bacterial peritonitis, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma) at VACS enrollment. Positive predictive values (PPVs) of diagnostic codes, laboratory abnormalities, and their combinations for confirmed outcomes were determined. Results Among 137 patients with a hepatic decompensation code and 197 with a laboratory abnormality, the diagnosis was confirmed in 57 (PPV, 42%; 95%CI, 33%-50%) and 56 (PPV, 28%; 95%CI, 22%-35%) patients, respectively. The combination of any code plus laboratory abnormality increased PPV (64%; 95%CI, 47%-79%). One inpatient or >= 2 outpatient diagnostic codes for ascites, spontaneous bacterial peritonitis, or variceal hemorrhage had high PPV (91%; 95%CI, 77%-98%) for confirmed hepatic decompensation events. Conclusion An algorithm of 1 inpatient or >= 2 outpatient codes for ascites, peritonitis, or variceal hemorrhage has sufficiently high PPV for hepatic decompensation to enable its use for epidemiologic research in VACS. This algorithm may be applicable to other cohorts. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Lo Re, Vincent, III; Dorey-Stein, Zachariah] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III; Dorey-Stein, Zachariah] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Lim, Joseph K.; Tate, Janet; Bathulapalli, Harini; Kidwai, Farah; Brandt, Cynthia; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Lim, Joseph K.; Tate, Janet; Bathulapalli, Harini; Kidwai, Farah; Brandt, Cynthia; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. [Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Klein, Marina B.] McGill Univ, Royal Victoria Hosp, Ctr Hlth, Montreal, PQ H3A 1A1, Canada. [Rimland, David] Atlanta VA Med Ctr, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Houston, TX 77030 USA. [Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Gibert, Cynthia L.] Washington DC VA Med Ctr, Washington, DC USA. [Gibert, Cynthia L.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Brown, Sheldon T.] James J Peters VA Med Ctr, New York, NY USA. [Brown, Sheldon T.] Mt Sinai Sch Med, New York, NY USA. RP Lo Re, V (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 836 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM vincentl@mail.med.upenn.edu RI Bathulapalli, Harini/B-7451-2015; Lo Re, Vincent/N-7817-2015 OI Goetz, Matthew/0000-0003-4542-992X FU National Institute of Allergy and Infectious Diseases [K01-AI070001]; National Institute on Alcohol Abuse and Alcoholism [U10-AA13566] FX This work was supported by the National Institute of Allergy and Infectious Diseases (grant number K01-AI070001 to Dr. Lo Re) and the National Institute on Alcohol Abuse and Alcoholism (U10-AA13566). The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 35 TC 34 Z9 34 U1 2 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JUL PY 2011 VL 20 IS 7 BP 689 EP 699 DI 10.1002/pds.2148 PG 11 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 800PE UT WOS:000293374600003 PM 21626605 ER PT J AU Wu, GF Corbo, E Schmidt, M Smith-Garvin, JE Riese, MJ Jordan, MS Laufer, TM Brown, EJ Maltzman, JS AF Wu, Gregory F. Corbo, Evann Schmidt, Michelle Smith-Garvin, Jennifer E. Riese, Matthew J. Jordan, Martha S. Laufer, Terri M. Brown, Eric J. Maltzman, Jonathan S. TI Conditional deletion of SLP-76 in mature T cells abrogates peripheral immune responses SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Knockout mice; Signal transduction; T cells ID PHOSPHOLIPASE C-GAMMA-1 PLC-GAMMA-1; CONTAINING LEUKOCYTE PROTEIN; HOMEOSTATIC PROLIFERATION; THYMOCYTE DEVELOPMENT; SIGNAL-TRANSDUCTION; MEDIATED ACTIVATION; ADAPTER; MICE; LAT; REQUIREMENT AB The adaptor protein Src homology 2 domain-containing leukocyte-specific protein of 76 kDa (SLP-76) is central to the organization of intracellular signaling downstream of the T-cell receptor (TCR). Evaluation of its role in mature, primary T cells has been hampered by developmental defects that occur in the absence of WT SLP-76 protein in thymocytes. Here, we show that following tamoxifen-regulated conditional deletion of SLP-76, mature, antigen-inexperienced T cells maintain normal TCR surface expression but fail to transduce TCR-generated signals. Conditionally deficient T cells fail to proliferate in response to antigenic stimulation or a lymphopenic environment. Mice with induced deletion of SLP-76 are resistant to induction of the CD4(+) T-cell-mediated autoimmune disease experimental autoimmune encephalomyelitis. Altogether, our findings demonstrate the critical role of SLP-76-mediated signaling in initiating T-cell-directed immune responses both in vitro and in vivo and highlight the ability to analyze signaling processes in mature T cells in the absence of developmental defects. C1 [Corbo, Evann; Schmidt, Michelle; Maltzman, Jonathan S.] Univ Penn, Sch Med, Dept Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. [Wu, Gregory F.] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Smith-Garvin, Jennifer E.; Jordan, Martha S.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Riese, Matthew J.] Univ Penn, Sch Med, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Laufer, Terri M.] Univ Penn, Sch Med, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Laufer, Terri M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Brown, Eric J.] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Brown, Eric J.] Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA. RP Maltzman, JS (reprint author), Univ Penn, Sch Med, Dept Med, Renal Electrolyte & Hypertens Div, 754 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM maltz@mail.med.upenn.edu FU NIH/NIAID [K08 AI055806, R01 AI085160, K01AR52802]; American Society of Nephrology/American Society of Transplantation; National Multiple Sclerosis Society FX We thank F. Costantini and G. Koretzky for providing mouse lines. We thank L. Kovoor for technical assistance. We thank D. Farber for critical review of this manuscript. This work was supported in part by grants from the NIH/NIAID (K08 AI055806 and R01 AI085160 to J. S. M. and K01AR52802 to M. S. J.) and the John Merrill Award from the American Society of Nephrology/American Society of Transplantation (to J. S. M.). G. F. W. and T. M. L. receive support from the National Multiple Sclerosis Society. NR 45 TC 11 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 2011 VL 41 IS 7 BP 2064 EP 2073 DI 10.1002/eji.201040809 PG 10 WC Immunology SC Immunology GA 797ME UT WOS:000293131200027 PM 21469089 ER PT J AU Dismuke, CE Egede, LE AF Dismuke, Clara E. Egede, Leonard E. TI Association of serious psychological distress with health services expenditures and utilization in a national sample of US adults SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Serious psychological distress; Health services expenditures; Utilization; US adults ID FACTOR SURVEILLANCE SYSTEM; MENTAL-HEALTH; SCREENING SCALES; UNITED-STATES; PREVALENCE; K6; PERFORMANCE; ARTHRITIS; OLDER; BRFSS AB Objective: The Kessler six-item scale has been shown to be a valid and reliable measure of serious psychological distress (SPD) in community samples. We examined the effect of SPD on health service expenditures and utilization for seven categories in a national probability sample of community dwelling adults in the United States. Methods: We used the two-step sample selection model to examine the association between SPD and total, office-based, outpatient, emergency department (ED), inpatient, dental, home health and prescription expenditures and utilization in 18,330 US adults who participated in the 2007 Medical Expenditure Panel Survey (MEPS). Results: SPD was significantly associated with $1735 (95% CI: $702-2769) higher total expenditures, $285 higher office expenditures ( 95% CI: $30-539), $183 higher ED expenditures (95% CI: $64-303), $282 (95% CI: $62-503) higher home health expenditures, $614 (95% CI: $403-825) higher prescription expenditures and $41 (95% CI: -$103 to $22) lower dental expenditures. SPD was associated with 3.09 (95% CI: 2.09-4.08) more office visits, 0.27 (95% CI: 0.17-0.36) more ED visits, 0.84 (95% CI: 0.36-1.32) more inpatient visits, 2.93 (95% CI: 0.13-5.70) more home health visits, 8.13 (95% CI: 6.08-10.18) more prescriptions and 0.18 (95% CI: -0.30 to -0.07) less dental visits. Conclusions: Among US adults, SPD is associated with significant increases in total expenditures and most other categories of expenditure and utilization. Targeted interventions to mitigate the adverse effects of SPD are needed. (C) 2011 Elsevier Inc. All rights reserved. C1 [Dismuke, Clara E.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. [Dismuke, Clara E.; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC 29401 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. EM egedel@musc.edu FU NIDDK NIH HHS [K24 DK093699] NR 34 TC 17 Z9 17 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JUL-AUG PY 2011 VL 33 IS 4 BP 311 EP 317 DI 10.1016/j.genhosppsych.2011.03.014 PG 7 WC Psychiatry SC Psychiatry GA 796LP UT WOS:000293053100002 PM 21762826 ER PT J AU Patterson, AL Morasco, BJ Fuller, BE Indest, DW Loftis, JM Hauser, P AF Patterson, Alexander L. Morasco, Benjamin J. Fuller, Bret E. Indest, David W. Loftis, Jennifer M. Hauser, Peter TI Screening for depression in patients with hepatitis C using the Beck Depression Inventory-II: do somatic symptoms compromise validity? SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Hepatitis C virus; Depression; Factor analysis; Liver disease; Beck Depression Inventory ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-LIFE; INTERFERON-ALPHA; VIRUS-INFECTION; UNITED-STATES; PSYCHIATRIC OUTPATIENTS; ANTIVIRAL THERAPY; CHRONIC PAIN; PREVALENCE; VETERANS AB Objective: The objective of the study was to evaluate the validity of the Beck Depression Inventory-II (BDI-II) when used to measure depression in patients with hepatitis C virus (HCV). Method: Factor analysis was utilized to validate the BDI-II in a sample of 671 patients with HCV recruited from a large Veterans Affairs medical center. The data were split randomly: the first half was subjected to exploratory factor analysis, and confirmatory factor analysis was used with the second half to confirm the model. Diagnostic data were retrieved from the electronic medical records. Results: Subjects were 97.0% male, average age was 52.8 years, 16.1% had a cirrhosis diagnosis, 62.9% had a current major depressive disorder diagnosis, and 42.3% endorsed significant depressive symptoms on the BDI-II. A two-factor model was an excellent fit for the data; the factors were labeled Cognitive Affective and Somatic. Patients scored significantly higher on the Somatic factor than on the Cognitive Affective factor (P<.001), and this discrepancy increased when comparing patients based on whether they had a diagnosis of cirrhosis. Conclusions: When screening for depression in HCV patients, questions targeting cognitive and affective symptoms of depression may provide a more valid measurement of depression than questions targeting somatic symptoms of depression, particularly for patients with more advanced liver disease. Published by Elsevier Inc. C1 [Patterson, Alexander L.; Morasco, Benjamin J.; Fuller, Bret E.; Indest, David W.; Loftis, Jennifer M.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Morasco, Benjamin J.; Fuller, Bret E.; Indest, David W.; Loftis, Jennifer M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Hauser, Peter] Long Beach VA Med Ctr, Long Beach, CA USA. RP Patterson, AL (reprint author), Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. EM alexander.patterson@va.gov NR 47 TC 19 Z9 19 U1 0 U2 2 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 JUL-AUG PY 2011 VL 33 IS 4 BP 354 EP 362 DI 10.1016/j.genhosppsych.2011.04.005 PG 9 WC Psychiatry SC Psychiatry GA 796LP UT WOS:000293053100008 PM 21762832 ER PT J AU Peralta, CA Katz, R DeBoer, I Ix, J Sarnak, M Kramer, H Siscovick, D Shea, S Szklo, M Shlipak, M AF Peralta, Carmen A. Katz, Ronit DeBoer, Ian Ix, Joachim Sarnak, Mark Kramer, Holly Siscovick, David Shea, Steven Szklo, Moyses Shlipak, Michael TI Racial and Ethnic Differences in Kidney Function Decline among Persons without Chronic Kidney Disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; NUTRITION EXAMINATION SURVEY; GLOMERULAR-FILTRATION-RATE; 3RD NATIONAL-HEALTH; SERUM CYSTATIN-C; CARDIOVASCULAR EVENTS; ATHEROSCLEROSIS MESA; SERIAL MEASUREMENTS; AFRICAN-AMERICANS; ELDERLY PERSONS AB Whether the rate of kidney function decline before the onset of CKD differs among racial and ethnic groups remains unclear. Here, we evaluated kidney function decline and incident CKD among white, black, Hispanic, and Chinese participants in the Multi-Ethnic Study of Atherosclerosis (MESA) during 5 years of follow-up. We estimated GFR using both cystatin C (eGFRcys) and creatinine (eGFRcreat). The definition of incident CKD required eGFRcys <60 ml/min per 1.73 m(2) and a decline in eGFRcys >= 1 ml/min per year. Among participants with eGFRcreat >60 ml/min per 1.73 m(2) at baseline, blacks had a significantly higher rate of kidney function decline than whites (0.31 ml/min per 1.73 m(2)/yr faster on average, P = 0.001), even after adjusting for multiple potential confounders. Among Hispanics, Dominicans and Puerto Ricans had faster rates of decline than whites (0.55 and 0.47 ml/min per 1.73 m(2)/yr faster, respectively). Mexicans, South Americans, or other Hispanics had similar rates of decline compared to whites. We did not detect significant differences in the rates of kidney function decline among Chinese and white participants. Among those with normal or near-normal kidney function at baseline, blacks and Hispanics had the highest rates of incident CKD during follow-up. Adjustment for comorbidities attenuated some of these differences. In conclusion, the average rate of kidney function decline before the onset of CKD differs among racial and ethnic groups. Traditional risk factors do not explain these differences fully, highlighting the need to explore these disparities. C1 [Peralta, Carmen A.; Shlipak, Michael] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Katz, Ronit] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [DeBoer, Ian] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Siscovick, David] Univ Washington, Dept Epidemiol & Biostat, Seattle, WA 98195 USA. [Ix, Joachim] Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA. [Sarnak, Mark] Tufts Univ New England Med Ctr, Div Nephrol, Boston, MA USA. [Kramer, Holly] Loyola Univ, Med Ctr, Div Nephrol, Maywood, IL 60153 USA. [Shea, Steven] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Szklo, Moyses] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Shlipak, Michael] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. RP Peralta, CA (reprint author), 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM Carmenalicia.peralta@ucsf.edu RI Inca, Inct/K-2204-2013 FU National Heart, Lung, and Blood Institute for MESA [N01-HC-95159, N01-HC-951651, N01-HC-95169]; NIDDK [IK23DK082793-01] FX This work was supported by contracts [N01-HC-95159 through N01-HC-951651 and [N01-HC-95169] from the National Heart, Lung, and Blood Institute for MESA. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhIbi.org. This work was also funded by the NIDDK (IK23DK082793-01 to C.P.) NR 31 TC 25 Z9 28 U1 0 U2 3 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 JUL PY 2011 VL 22 IS 7 BP 1327 EP 1334 DI 10.1681/ASN.2010090960 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 798KA UT WOS:000293203400020 PM 21700831 ER PT J AU Hegde, M Glass, GA Dalmau, J Christine, CW AF Hegde, Manu Glass, Graham A. Dalmau, Josep Christine, Chadwick W. TI A Case of Slow Orthostatic Tremor, Responsive to Intravenous Immunoglobulin SO MOVEMENT DISORDERS LA English DT Letter C1 [Hegde, Manu; Glass, Graham A.; Christine, Chadwick W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Glass, Graham A.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. [Dalmau, Josep] Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. RP Hegde, M (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. EM manu.hegde@ucsf.edu OI Dalmau, Josep/0000-0001-5856-2813 FU NINDS NIH HHS [5U10NS044460, R01NS046487] NR 7 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL PY 2011 VL 26 IS 8 BP 1563 EP 1565 DI 10.1002/mds.23610 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 800CB UT WOS:000293334800038 PM 21469203 ER PT J AU Donahue, TR Isacoff, WH Hines, OJ Tomlinson, JS Farrell, JJ Bhat, YM Garon, E Clerkin, B Reber, HA AF Donahue, Timothy R. Isacoff, William H. Hines, O. Joe Tomlinson, James S. Farrell, James J. Bhat, Yasser M. Garon, Edward Clerkin, Barbara Reber, Howard A. TI Downstaging Chemotherapy and Alteration in the Classic Computed Tomography/Magnetic Resonance Imaging Signs of Vascular Involvement in Patients With Pancreaticobiliary Malignant Tumors Influence on Patient Selection for Surgery SO ARCHIVES OF SURGERY LA English DT Article ID PHASE HELICAL CT; MULTIDETECTOR CT; CANCER; ADENOCARCINOMA; PANCREAS; SURVIVAL; PANCREATICODUODENECTOMY; CHOLANGIOCARCINOMA; UNRESECTABILITY; CHEMORADIATION AB Objectives: To determine whether computed tomography (CT)/magnetic resonance imaging (MRI) signs of vascular involvement are accurate after downstaging chemotherapy (DCTx) and to highlight factors associated with survival in patients who have undergone resection. Design: Retrospective cohort study; prospective database. Setting: University pancreatic disease center. Patients: Patients with unresectable pancreaticobiliary cancer who underwent curative intent surgery after completing DCTx. Interventions: Use of CT/MRI scan, pancreatic resection, and palliative bypass. Main Outcome Measures: Resectability after DCTx and disease-specific survival. Results: We operated on 41 patients (1992-2009) with locally advanced periampullary malignant tumors after a median of 8.5 months of DCTx. Before DCTx, most patients (38 [93%]) were unresectable because of evidence of vascular contact on CT/MRI scan or operative exploration. Criteria for exploration after DCTx were CT/MRI evidence of tumor shrinkage and/or change in signs of vascular involvement, cancer antigen 19-9 decrease, and good functional status. None had progressive disease. At operation, we resected tumors in 34 of 41 patients (83%), and 6 had persistent vascular involvement. Surprisingly, CT/MRI scan was only 71% sensitive and 58% specific to detect vascular involvement after DCTx. "Involvement" on imaging was often from tumor fibrosis rather than viable cancer. Radiographic decrease in tumor size also did not predict resectability (P=.10). Patients with tumors that were resected had a median 87% decrease in cancer antigen 19-9 (P=.04) during DCTx. The median follow-up (all survivors) was 31 months, and disease-specific survival was 52 months for patients with resected tumors. Conclusions: In patients with initially unresectable periampullary malignant tumors, original CT/MRI signs of vascular involvement may persist after successful DCTx. Patients should be chosen for surgery on the basis of lack of disease progression, good functional status, and decrease in cancer antigen 19-9. C1 [Donahue, Timothy R.; Hines, O. Joe; Clerkin, Barbara; Reber, Howard A.] Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Div Gen Surg, Los Angeles, CA 90095 USA. [Isacoff, William H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Tomlinson, James S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg Oncol, Los Angeles, CA 90095 USA. [Farrell, James J.; Bhat, Yasser M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Garon, Edward] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Dept Med, Los Angeles, CA 90095 USA. [Tomlinson, James S.; Farrell, James J.] Greater Los Angeles Vet Healthcare Syst, Los Angeles, CA USA. RP Donahue, TR (reprint author), Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Div Gen Surg, 72-215 CHS,10833 LeConte Ave, Los Angeles, CA 90095 USA. EM tdonahue@mednet.ucla.edu NR 28 TC 27 Z9 27 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUL PY 2011 VL 146 IS 7 BP 836 EP 843 PG 8 WC Surgery SC Surgery GA 794EH UT WOS:000292877800015 PM 21768431 ER PT J AU Hsu, HC Yang, P Wu, Q Wang, JH Job, G Guentert, T Li, J Stockard, CR Le, TVL Chaplin, DD Grizzle, WE Mountz, JD AF Hsu, Hui-Chen Yang, PingAr Wu, Qi Wang, John H. Job, Godwin Guentert, Tanja Li, Jun Stockard, Cecil R. Le, Thuc-vy L. Chaplin, David D. Grizzle, William E. Mountz, John D. TI Inhibition of the Catalytic Function of Activation-Induced Cytidine Deaminase Promotes Apoptosis of Germinal Center B Cells in BXD2 Mice SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CYCLIC CITRULLINATED PEPTIDE; CLASS SWITCH RECOMBINATION; RHEUMATOID-ARTHRITIS; SOMATIC HYPERMUTATION; PATHOGENIC AUTOANTIBODIES; AUTOIMMUNE-DISEASE; MEDIATED APOPTOSIS; EROSIVE ARTHRITIS; MRL/LPR MICE AB Objective. To determine whether functional suppression of the catalytic domain of activation-induced cytidine deaminase (AID) can suppress the hyperreactive germinal center (GC) responses in BXD2 mice. Methods. We generated transgenic BXD2 mice expressing a dominant-negative (DN) form of Aicda at the somatic hypermutation site (BXD2-Aicda-DN-transgenic mice). Real-time quantitative reverse transcriptase polymerase chain reaction was used to determine the expression of Aicda and DNA damage/repair genes. Enzyme-linked immunosorbent assay was used to measure serum levels of autoantibodies and immune complexes (ICs). Development of GCs and antibody-containing ICs as well as numbers of proliferative and apoptotic cells were determined using flow cytometry and/or immunohistochemical analyses. Development of arthritis and kidney disease was evaluated histologically in 6-8-month-old mice. Results. Suppression of the somatic hypermutation function of AID resulted in a significant decrease in autoantibody production without affecting the expression of DNA damage related genes in GC B cells of BXD2-Aicda-DN-transgenic mice. There was decreased proliferation, increased apoptosis, increased expression of caspase 9 messenger RNA in GC B cells, and lower numbers of GCs in the spleens of BXD2-Aicda-DN-transgenic mice. Decreased GC response was associated with lower levels of IgG-containing ICs. Anti-IgM- and anti-CD40 plus anti-Ig-induced B cell proliferative responses were decreased in BXD2-Aicda-DN-transgenic mice. Conclusion. Inhibition of the AID somatic hypermutation function in BXD2 mice suppressed development of spontaneous GCs, generation of autoantibody-producing B cells, and autoimmunity in BXD2 mice. Suppression of AID catalytic function to limit selection-based survival of GC B cells could become a novel therapy for the treatment of autoimmune disease. C1 [Mountz, John D.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Le, Thuc-vy L.] Emory Univ, Atlanta, GA 30322 USA. [Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Mountz, JD (reprint author), Univ Alabama Birmingham, Dept Med, 1825 Univ Blvd,SHELB 307, Birmingham, AL 35294 USA. EM jdmountz@uab.edu OI Chaplin, David/0000-0002-1354-3069 FU Lupus Research Institute; Arthritis Foundation; American College of Rheumatology Research and Education Foundation; Alliance for Lupus Research; Department of Veterans Affairs [1I01BX000600-01]; Daiichi-Sankyo Co., Ltd; NIH [1-AI-071110-01A1, ARRA-3-R01-AI-71110-02S1] FX Supported by grants to Dr. Hsu from the Lupus Research Institute (Novel Research project grant) and the Arthritis Foundation (Arthritis Investigator Award) and by grants to Dr. Mountz from the American College of Rheumatology Research and Education Foundation (Within Our Reach research grant), the Alliance for Lupus Research (Target Identification in Lupus program grant), the Department of Veterans Affairs (Merit Review grant 1I01BX000600-01), Daiichi-Sankyo Co., Ltd, and the NIH (grants 1-AI-071110-01A1 and ARRA-3-R01-AI-71110-02S1). NR 50 TC 20 Z9 20 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JUL PY 2011 VL 63 IS 7 BP 2038 EP 2048 DI 10.1002/art.30257 PG 11 WC Rheumatology SC Rheumatology GA 793GZ UT WOS:000292809700034 PM 21305519 ER PT J AU Au, K Singh, MK Bodukam, V Bae, S Maranian, P Ogawa, R Spiege, B McMahon, M Hahn, B Khanna, D AF Au, Karen Singh, Manjit K. Bodukam, Vijay Bae, Sangmee Maranian, Paul Ogawa, Rikke Spiege, Brennan McMahon, Maureen Hahn, Bevra Khanna, Dinesh TI Atherosclerosis in Systemic Sclerosis A Systematic Review and Meta-Analysis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INTIMA-MEDIA THICKNESS; HIGH-DENSITY-LIPOPROTEIN; BRAIN MAGNETIC-RESONANCE; LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; MACROVASCULAR DISEASE; ENDOTHELIAL DYSFUNCTION; SUBCLINICAL ATHEROSCLEROSIS; CORONARY ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION AB Objective. Systemic sclerosis (SSc) is characterized by calcification, vasculopathy, and endothelial wall damage, all of which can increase the risk of developing atherosclerosis and cardiovascular disease. The aim of this study was to perform a systematic review and meta-analysis to determine whether the risk of atherosclerosis is increased in SSc patients compared to healthy individuals. Methods. A systematic search was performed to identify studies published in PubMed and the Cochrane database up to May 2010, and recently published abstracts were also reviewed. Two reviewers independently screened articles to identify studies comparing the rate of atherosclerosis in SSc patients to that in healthy controls. The studies utilized one of the following methods: angiography, Doppler ultrasound to assess plaque and carotid intima-media thickness (IMT), computed tomography, magnetic resonance imaging, flow-mediated vasodilation (assessed as the FMD%), the ankle brachial index, or autopsy. For carotid IMT and FMD% values, we computed a pooled estimate of the summary mean difference and explored predictors of carotid IMT using random-effects meta-regression. Results. Of the 3,156 articles initially identified, 31 were selected for systematic review. The meta-analysis included 14 studies assessing carotid IMT and 7 assessing brachial artery FMD%. Compared to healthy controls, SSc patients had a higher prevalence of coronary atherosclerosis, peripheral vascular disease, and cerebrovascular calcification. Meta-analysis showed that SSc patients had increased carotid IMT (summary mean difference 0.11 mm, 95% confidence interval [95% CI] 0.05 mm, 0.17 mm; P = 0.0006) and lower FMD% (summary mean difference -3.07%, 95% CI -5.44%, -0.69%; P = 0.01) compared to controls. There was marked heterogeneity between the studies, which was mainly attributable to variations in disease duration and differences in the mean/median age between SSc patients and controls. Conclusion. Patients with SSc have an increased risk of atherosclerosis compared to healthy subjects. Further studies should elucidate the mechanism of this increased risk. C1 [Khanna, Dinesh] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Spiege, Brennan] VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA USA. RP Khanna, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Rheumatol, 1000 Vet Ave,Room 32-59 Rehabil Bldg, Los Angeles, CA 90095 USA. EM dkhanna@mednet.ucla.edu RI Ogawa, Rikke/I-2538-2013 OI Ogawa, Rikke/0000-0003-2681-8794 FU American College of Rheumatology Research and Education Foundation; Scleroderma Foundation; NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [K23-AR-053858-04] FX Dr. Au's work was supported by the American College of Rheumatology Research and Education Foundation (Physician Scientist Development Award) and the Scleroderma Foundation. Dr. Khanna's work was supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant K23-AR-053858-04). NR 67 TC 51 Z9 53 U1 0 U2 12 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 JUL PY 2011 VL 63 IS 7 BP 2078 EP 2090 DI 10.1002/art.30380 PG 13 WC Rheumatology SC Rheumatology GA 793GZ UT WOS:000292809700038 PM 21480189 ER PT J AU Sahul, ZH Mukherjee, R Song, J McAteer, J Stroud, RE Dione, DP Staib, L Papademetris, X Dobrucki, LW Duncan, JS Spinale, FG Sinusas, AJ AF Sahul, Zakir H. Mukherjee, Rupak Song, James McAteer, Jarod Stroud, Robert E. Dione, Donald P. Staib, Lawrence Papademetris, Xenophon Dobrucki, Lawrence W. Duncan, James S. Spinale, Francis G. Sinusas, Albert J. TI Targeted Imaging of the Spatial and Temporal Variation of Matrix Metalloproteinase Activity in a Porcine Model of Postinfarct Remodeling Relationship to Myocardial Dysfunction SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE matrix metalloproteinases; ventricular remodeling; imaging ID LEFT-VENTRICULAR ENLARGEMENT; CLINICAL-IMPLICATIONS; TISSUE INHIBITOR; HEART-FAILURE; INFARCT SIZE; MATRIX-METALLOPROTEINASE-9; ACTIVATION; RECEPTOR; MICE; RAT AB Background-Matrix metalloproteinases (MMPs) are known to modulate left ventricular (LV) remodeling after a myocardial infarction (MI). However, the temporal and spatial variation of MMP activation and their relationship to mechanical dysfunction after MI remain undefined. Methods and Results-MI was surgically induced in pigs (n=23) and cine magnetic resonance (MR) and dual-isotope hybrid single-photon emission CT (SPECT)/CT imaging obtained using thallium-201 and a technetium-99m-labeled MMP targeted tracer ((99m)Tc-RP805) at 1, 2, and 4 weeks post-MI along with controls (n=5). Regional myocardial strain was computed from MR images and related to MMP zymography and ex vivo myocardial (99m)Tc-RP805 retention. MMP activation as assessed by in vivo and ex vivo (99m)Tc-RP805 imaging and retention studies was increased nearly 4-fold within the infarct region at 1 week post-MI and remained elevated up to 1 month post-MI. The post-MI change in LV end-diastolic volumes was correlated with MMP activity (y=31.34e(0.48x), P=0.04). MMP activity was increased within the border and remote regions early post-MI, but declined over 1 month. There was a high concordance between regional (99m)Tc-RP805 uptake and ex vivo MMP-2 activity. Conclusions-A novel, multimodality, noninvasive hybrid SPECT/CT imaging approach was validated and applied for in vivo evaluation of MMP activation in combination with cine MR analysis of LV deformation. Increased (99m)Tc-RP805 retention was seen throughout the heart early post-MI and was not purely a reciprocal of thallium-201 perfusion. The (99m)Tc-RP805 SPECT/CT imaging may provide unique information regarding regional myocardial MMP activation and predict late post-MI LV remodeling. (Circ Cardiovasc Imaging. 2011;4:381-391.) C1 [Sahul, Zakir H.; Song, James; McAteer, Jarod; Dione, Donald P.; Dobrucki, Lawrence W.; Duncan, James S.; Sinusas, Albert J.] Yale Univ, Sch Med, Expt Nucl Cardiol Lab, New Haven, CT 06520 USA. [Staib, Lawrence; Papademetris, Xenophon; Sinusas, Albert J.] Yale Univ, Sch Med, Div Cardiovasc Med, Dept Internal Med, New Haven, CT 06520 USA. [Staib, Lawrence; Papademetris, Xenophon; Sinusas, Albert J.] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06520 USA. [Mukherjee, Rupak; Stroud, Robert E.; Spinale, Francis G.] Med Univ S Carolina, Charleston, SC 29425 USA. [Mukherjee, Rupak; Stroud, Robert E.; Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Sinusas, AJ (reprint author), Yale Univ, Sch Med, Expt Nucl Cardiol Lab, 3FMP,POB 208017, New Haven, CT 06520 USA. EM albert.sinusas@yale.edu OI Staib, Lawrence/0000-0002-9516-5136; Dobrucki, Wawrzyniec/0000-0002-6807-217X FU National Institutes of Health [HL078650, HL078825, HL057952, HL059165, HL095608]; Research Service of the Department of Veterans Affairs FX This work was supported by National Institutes of Health grants HL078650, HL078825, HL057952, HL059165, and HL095608 and the Research Service of the Department of Veterans Affairs. The 99mTc-RP805 used in this study was provided in kind by Lantheus Medical Imaging. NR 28 TC 38 Z9 38 U1 0 U2 6 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 JUL PY 2011 VL 4 IS 4 BP 381 EP 391 DI 10.1161/CIRCIMAGING.110.961854 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 794BV UT WOS:000292871000007 PM 21505092 ER PT J AU Freiberg, MS Chang, CCH Skanderson, M McGinnis, K Kuller, LH Kraemer, KL Rimland, D Goetz, MB Butt, AA Barradas, MCR Gibert, C Leaf, D Brown, ST Samet, J Kazis, L Bryant, K Justice, AC AF Freiberg, Matthew S. Chang, Chung-Chou H. Skanderson, Melissa McGinnis, Kathleen Kuller, Lewis H. Kraemer, Kevin L. Rimland, David Goetz, Matthew B. Butt, Adeel A. Barradas, Maria C. Rodriguez Gibert, Cynthia Leaf, David Brown, Sheldon T. Samet, Jeffrey Kazis, Lewis Bryant, Kendall Justice, Amy C. CA Vet Aging Cohort Study TI The Risk of Incident Coronary Heart Disease Among Veterans With and Without HIV and Hepatitis C SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE viruses; coronary disease; mortality; comorbidity ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACUTE MYOCARDIAL-INFARCTION; MICROBIAL TRANSLOCATION; CARDIOVASCULAR-DISEASE; INFECTED INDIVIDUALS; ARTERY-DISEASE; ASSOCIATION; SEROPOSITIVITY; ATHEROSCLEROSIS; PREVALENCE AB Background-Whether hepatitis C virus (HCV) confers additional coronary heart disease (CHD) risk among human immunodeficiency virus (HIV) infected individuals is unclear. Without appropriate adjustment for antiretroviral therapy, CD4 count, and HIV-1 RNA and substantially different mortality rates among those with and without HIV and HCV infection, the association between HIV, HCV, and CHD may be obscured. Methods and Results-We analyzed data on 8579 participants (28% HIV+, 9% HIV + HCV+) from the Veterans Aging Cohort Study Virtual Cohort who participated in the 1999 Large Health Study of Veteran Enrollees. We analyzed data collected on HIV and HCV status, risk factors for and the incidence of CHD, and mortality from January 2000 to July 2007. We compared models to assess CHD risk when death was treated as a censoring event and as a competing risk. During the median 7.3 years of follow-up, there were 194 CHD events and 1186 deaths. Compared with HIV - HCV - Veterans, HIV + HCV + Veterans had a significantly higher risk of CHD regardless of whether death was adjusted for as a censoring event (adjusted hazard ratio, 2.03; 95% confidence interval, 1.28 to 3.21) or a competing risk (adjusted HR, 2.45; 95% confidence interval, 1.83 to 3.27 respectively). Compared with HIV - HCV - Veterans, HIV + HCV + Veterans also had a significantly higher adjusted risk of CHD regardless of whether death was treated as a censored event (adjusted hazard ratio, 1.93; 95% confidence interval, 1.02 to 3.62) or a competing risk (adjusted hazard ratio, 1.46; 95% confidence interval, 1.03 to 2.07). Conclusions-HIV + HCV + Veterans have an increased risk of CHD compared with HIV + HCV - and HIV - HCV - Veterans. (Circ Cardiovasc Qual Outcomes. 2011;4:425-432.) C1 [Freiberg, Matthew S.; Chang, Chung-Chou H.; Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Freiberg, Matthew S.; Chang, Chung-Chou H.; Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Skanderson, Melissa; McGinnis, Kathleen; Justice, Amy C.] W Haven Vet Adm Med Ctr, VA Connecticut Hlth Care Syst, West Haven, CT USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Rimland, David] Atlanta Vet Adm Med Ctr, Atlanta, GA USA. [Goetz, Matthew B.; Leaf, David] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Goetz, Matthew B.; Leaf, David] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90095 USA. [Butt, Adeel A.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Barradas, Maria C. Rodriguez] Baylor Coll Med, Houston, TX 77030 USA. [Barradas, Maria C. Rodriguez] Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA. [Gibert, Cynthia] George Washington Univ, Sch Med, Washington, DC USA. [Gibert, Cynthia] Washington DC Vet Adm Med Ctr, Washington, DC USA. [Brown, Sheldon T.] James J Peters VA Bronx, New York, NY USA. [Brown, Sheldon T.] Mt Sinai Sch Med, New York, NY USA. [Samet, Jeffrey] Boston Univ, Sch Med, Boston, MA 02118 USA. [Kazis, Lewis] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Bryant, Kendall] NIAAA, Bethesda, MD USA. [Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. RP Freiberg, MS (reprint author), Univ Pittsburgh, Sch Med, 230 McKee Pl, Pittsburgh, PA 15213 USA. EM freibergms@upmc.edu OI Kazis, Lewis/0000-0003-1800-5849; Samet, Jeffrey/0000-0002-0897-3400; Goetz, Matthew/0000-0003-4542-992X FU National Institute on Alcohol Abuse and Alcoholism [2U10 AA 13566, K23 AA015914]; National Heart, Lung, and Blood Institute [1RO1HL095136-03] FX This study was supported by the National Institute on Alcohol Abuse and Alcoholism (2U10 AA 13566 and K23 AA015914) and the National Heart, Lung, and Blood Institute (1RO1HL095136-03). NR 33 TC 55 Z9 57 U1 1 U2 4 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 JUL PY 2011 VL 4 IS 4 BP 425 EP 432 DI 10.1161/CIRCOUTCOMES.110.957415 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 794CH UT WOS:000292872500009 PM 21712519 ER PT J AU Patil, VK St Andre, JR Crisan, E Smith, BM Evans, CT Steiner, ML Pape, TL AF Patil, Vijaya K. St Andre, Justin R. Crisan, Elena Smith, Bridget M. Evans, Charlesnika T. Steiner, Monica L. Pape, Theresa L. TI Prevalence and Treatment of Headaches in Veterans With Mild Traumatic Brain Injury SO HEADACHE LA English DT Article DE headache; brain injury; veteran; blast injury ID PERSISTENT POSTCONCUSSIVE SYMPTOMS; POSTTRAUMATIC-STRESS-DISORDER; POLYTRAUMA CLINICAL TRIAD; US SOLDIERS; CHRONIC PAIN; HEAD-INJURY; IRAQ; EPIDEMIOLOGY; AFGHANISTAN; WAR AB Objectives.-To report the prevalence and characteristics of headaches in veterans with mild traumatic brain injury (TBI) and to describe most common treatment strategies after neurological evaluation. Methods.-We conducted a retrospective cohort study. The setting was a United States Veterans Healthcare Administration Polytrauma Network Site. The study participants consisted of 246 veterans with confirmed diagnosis of mild TBI. The main outcome measures were: Self-reported head pain occurring 30 days prior to initial mild TBI screening; headache severity measured by the Neurobehavioral Symptom Inventory; headache characteristics; and treatment prescribed by neurologists. Results.-The majority (74%) of veterans with a confirmed diagnosis of mild TBI (N = 246), due largely to blast exposure, reported headaches in the 30 days preceding the initial mild TBI evaluation. Thirty-three percent of these veterans (N = 81) were referred to neurology for persistent headaches. Of the 56 veterans attending the neurology evaluation, 45% were diagnosed with migraine headaches and 20% with chronic daily headaches. The most commonly used abortive agents were triptans (68%) and the most common preventive medications were anticonvulsants (55%) and tricyclics (40%). Conclusion.-There was an increased prevalence of headaches in veterans with mild TBI. Most of the TBI veterans in our study group were exposed to blast injury and findings indicate that the nature of head trauma may be contributing to headaches. Findings highlight the need for developing effective headache prevention and treatment strategies for all persons with mild TBI and in particular for veterans with blast-related mild TBI. C1 [St Andre, Justin R.; Smith, Bridget M.; Evans, Charlesnika T.; Pape, Theresa L.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Patil, Vijaya K.; Crisan, Elena] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Neurol, Hines, IL 60141 USA. [Steiner, Monica L.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Phys Med & Rehabil, Hines, IL 60141 USA. [Patil, Vijaya K.; Crisan, Elena; Smith, Bridget M.; Steiner, Monica L.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Evans, Charlesnika T.] Northwestern Univ, Inst Healthcare Studies, Feinberg Sch Med, Chicago, IL 60611 USA. [Pape, Theresa L.] Northwestern Univ, Dept Phys Med & Rehabil, Feinberg Sch Med, Chicago, IL 60611 USA. RP Patil, VK (reprint author), Edward Hines Jr VA Hosp, Dept Neurol, Bldg 228,5th Floor,5000A,M-C 127,POB 5000, Hines, IL 60141 USA. EM vijaya.patil2@va.gov OI Pape, Theresa/0000-0001-7738-5963 FU Department of Veterans Affairs; Office of Research and Development, Health Services Research and Development Service [IIR 07-188-3]; Locally-Initiated [42-533]; Edward Hines Jr. VA Hospital, Center for Management of Complex Chronic Care (CMC3) FX This study was supported by the Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service as grant IIR 07-188-3, Locally-Initiated Project 42-533 and the Edward Hines Jr. VA Hospital, Center for Management of Complex Chronic Care (CMC3). 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 35 TC 15 Z9 15 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-8748 J9 HEADACHE JI Headache PD JUL-AUG PY 2011 VL 51 IS 7 BP 1112 EP 1121 DI 10.1111/j.1526-4610.2011.01946.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 793ZD UT WOS:000292862100006 PM 21762135 ER PT J AU Kim, JH Toy, D Muder, RR AF Kim, Jong Hun Toy, Diana Muder, Robert R. TI Clostridium difficile Infection in a Long-Term Care Facility: Hospital-Associated Illness Compared with Long-Term Care-Associated Illness SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID DIARRHEA; EPIDEMIOLOGY; DISEASE; SURVEILLANCE; DIAGNOSIS; COLITIS; TIME AB BACKGROUND. Controversy exists over whether Clostridium difficile infection (CDI) commonly occurs in long-term care facility residents who have not been recently transferred from an acute care hospital. objective. To assess the incidence and outcome of CDI in a long-term care facility. METHODS. Retrospective cohort study in a 262-bed long-term care Veterans Affairs facility in Pittsburgh, Pennsylvania, for the period January 2004 through June 2010. CDI was identified by positive stool C. difficile toxin assay and acute diarrhea. Patients were categorized as hospital-associated CDI (HACDI) or long-term care facility-associated CDI (LACDI) and followed for 6 months. RESULTS. The annual rate of CDI varied between 0.11 and 0.23 per 1,000 resident-days for HACDI patients and between 0.04 and 0.28 per 1,000 resident-days for LACDI patients. We identified 162 patients, 96 patients (59.3%) with HACDI and 66 patients (40.7%) with LACDI. Median age was 74 and 77 years, respectively, for HACDI and LACDI (P = .055) patients. There were more patients with at least 1 relapse of CDI during 6 months of follow up in LACDI patients (32/66, 48.5%) than in HACDI patients (28/96, 29.2%; P = .009). Logistic regression showed that ages of at least 75 years (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.07-5.07; P = .033), more than 2 transfers to an acute care hospital (OR, 7.88; 95% CI, 1.88-32.95; P = .005), and LACDI (OR, 3.15; 95% CI, 1.41-7.05; P = .005) were associated with relapse of CDI. CONCLUSIONS. Forty percent of CDI cases were acquired within the long-term care facility, indicating a substantial degree of transmission. Optimal strategies to prevent CDI in the long-term care facility are needed. Infect Control Hosp Epidemiol 2011;32(7):656-660 C1 [Toy, Diana; Muder, Robert R.] VA Pittsburgh Healthcare Syst, Infect Dis Sect, VA Med Ctr, Pittsburgh, PA 15240 USA. [Kim, Jong Hun; Muder, Robert R.] Univ Pittsburgh, Med Ctr, Div Infect Dis, Pittsburgh, PA USA. RP Muder, RR (reprint author), VA Pittsburgh Healthcare Syst, Infect Dis Sect, VA Med Ctr, Univ Dr C, Pittsburgh, PA 15240 USA. EM robert.muder@va.gov FU Department of Veterans Affairs FX This work was supported by the Department of Veterans Affairs. NR 19 TC 23 Z9 23 U1 1 U2 9 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 JUL PY 2011 VL 32 IS 7 BP 656 EP 660 DI 10.1086/660767 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 795LR UT WOS:000292976200004 PM 21666395 ER PT J AU Imel, ZE Baldwin, S Atkins, DC Owen, J Baardseth, T Wampold, BE AF Imel, Zac E. Baldwin, Scott Atkins, David C. Owen, Jesse Baardseth, Tim Wampold, Bruce E. TI Racial/Ethnic Disparities in Therapist Effectiveness: A Conceptualization and Initial Study of Cultural Competence SO JOURNAL OF COUNSELING PSYCHOLOGY LA English DT Article DE cultural competence; health disparities; multilevel modeling; therapist effects ID MULTICULTURAL COUNSELING COMPETENCES; YOUTH TREATMENT CYT; HEALTH-CARE; MODEL; INTERVENTIONS; PROVIDER; OUTCOMES; CLIENTS; DESIGN AB As a result of mental health disparities between White and racial/ethnic minority clients, researchers have argued that some therapists may be generally competent to provide effective services but lack cultural competence. This distinction assumes that client racial/ethnic background is a source of variability in therapist effectiveness. However, there have been no direct tests of the therapist as a source of health disparities. We provided an initial test of the distinction between general and cultural competence by examining client racial/ethnic background as a source of variability in therapist effectiveness. We analyzed cannabis use outcomes from a psychotherapy trial (N = 582) for adolescent cannabis abuse and dependence using Bayesian multilevel models for count outcomes. We first tested whether therapists differed in their effectiveness and then tested whether disparities in treatment outcomes varied across therapist caseloads. Results suggested that therapists differed in their effectiveness in general and that effectiveness varied according to client racial/ethnic background. Therapist effectiveness may depend partially on client racial/ethnic minority background, providing evidence that it is valid to distinguish between general and cultural competence. C1 [Imel, Zac E.; Baardseth, Tim; Wampold, Bruce E.] Univ Wisconsin, Dept Counseling Psychol, Madison, WI 53706 USA. [Baldwin, Scott] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Atkins, David C.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Owen, Jesse] Univ Louisville, Dept Counseling Psychol, Louisville, KY 40292 USA. RP Imel, ZE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, S-116 MHC,1660 S Columbian Way, Seattle, WA 98116 USA. EM zeimel@u.washington.edu RI Baldwin, Scott/G-4021-2017 OI Baldwin, Scott/0000-0003-3428-0437; imel, zachary/0000-0001-9645-7184; Atkins, David/0000-0002-5781-9880 NR 43 TC 23 Z9 23 U1 2 U2 13 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-0167 J9 J COUNS PSYCHOL JI J. Couns. Psychol. PD JUL PY 2011 VL 58 IS 3 BP 290 EP 298 DI 10.1037/a0023284 PG 9 WC Psychology, Educational; Psychology, Applied SC Psychology GA 792SC UT WOS:000292768500002 PM 21534654 ER PT J AU Robinson, TN Wallace, JI Wu, DS Wiktor, A Pointer, LF Pfister, SM Sharp, TJ Buckley, MJ Moss, M AF Robinson, Thomas N. Wallace, Jeffrey I. Wu, Daniel S. Wiktor, Arek Pointer, Lauren F. Pfister, Shirley M. Sharp, Terra J. Buckley, Mary J. Moss, Marc TI Accumulated Frailty Characteristics Predict Postoperative Discharge Institutionalization in the Geriatric Patient SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 118th Scientific Session of the Western-Surgical-Association CY NOV, 2010 CL Chicago, IL SP Western Surg Assoc ID ELDERLY-PEOPLE; OLDER-ADULTS; CO-MORBIDITY; OUTCOMES; VALIDATION; SURGERY; AGE AB BACKGROUND: Frailty is a state of increased vulnerability to health-related stressors and can be measured by summing the number of frailty characteristics present in an individual. Discharge institutionalization (rather than discharge to home) represents disease burden and functional dependence after hospitalization. Our aim was to determine the relationship between frailty and need for postoperative discharge institutionalization. STUDY DESIGN: Subjects >= 65 years undergoing major elective operations requiring postoperative ICU admission were enrolled. Discharge institutionalization was defined as need for institutionalized care at hospital discharge. Fourteen preoperative frailty characteristics were measured in 6 domains: comorbidity burden, function, nutrition, cognition, geriatric syndromes, and extrinsic frailty. RESULTS: A total of 223 subjects (mean age 73 +/- 6 years) were studied. Discharge institutionalization occurred in 30% (n = 66). Frailty characteristics related to need for postoperative discharge institutionalization included: older age, Charlson index >= 3, hematocrit <35%, any functional dependence, up-and-go >= 15 seconds, albumin <3.4 mg/dL, Mini-Cog score <= 3, and having fallen within 6 months (p < 0.0001 for all comparisons). Multivariate logistic regression retained prolonged timed up-and-go (p < 0.0001) and any functional dependence (p < 0.0001) as the variables most closely related to need for discharge institutionalization. An increased number of frailty characteristics present in any one subject resulted in increased rate of discharge institutionalization. CONCLUSIONS: Nearly 1 in 3 geriatric patients required discharge to an institutional care facility after major surgery. The frailty characteristics of prolonged up-and-go and any functional dependence were most closely related to the need for discharge institutionalization. Accumulation of a higher number of frailty characteristics in any one geriatric patient increased their risk of discharge institutionalization. (J Am Coll Surg 2011; 213: 37-44. (C) 2011 by the American College of Surgeons) C1 [Robinson, Thomas N.; Wu, Daniel S.; Wiktor, Arek] Univ Colorado, Denver Sch Med, Dept Surg, Aurora, CO USA. [Wallace, Jeffrey I.; Moss, Marc] Univ Colorado, Denver Sch Med, Dept Med, Aurora, CO USA. [Robinson, Thomas N.; Wu, Daniel S.; Wiktor, Arek] Denver Vet Affairs Med Ctr, Dept Surg, Denver, CO USA. [Pointer, Lauren F.] Denver Vet Affairs Med Ctr, Dept Biostat, Denver, CO USA. [Pfister, Shirley M.; Sharp, Terra J.; Buckley, Mary J.] Denver Vet Affairs Med Ctr, Dept Anesthesia, Denver, CO USA. RP Robinson, TN (reprint author), 12631 E 17th Ave,MS C313, Aurora, CO 80045 USA. EM thomas.robinson@ucdenver.edu FU NHLBI NIH HHS [K24 HL089223, K24 HL089223-04, K24 HL089223-05, K24-HL-089223]; NIA NIH HHS [K23 AG034632, K23 AG034632-01A1, K23AG034632] NR 30 TC 106 Z9 107 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUL PY 2011 VL 213 IS 1 BP 37 EP 42 DI 10.1016/j.jamcollsurg.2011.01.056 PG 6 WC Surgery SC Surgery GA 794SU UT WOS:000292922400009 PM 21435921 ER PT J AU Stengel, A Goebel-Stengel, M Wang, L Luckey, A Hu, E Rivier, J Tache, Y AF Stengel, A. Goebel-Stengel, M. Wang, L. Luckey, A. Hu, E. Rivier, J. Tache, Y. TI Central administration of pan-somatostatin agonist ODT8-SST prevents abdominal surgery-induced inhibition of circulating ghrelin, food intake and gastric emptying in rats SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE acyl ghrelin; food intake; gastric emptying; postoperative gastric ileus; somatostatin agonist; somatostatin-28 ID CORTICOTROPIN-RELEASING-FACTOR; CENTRAL-NERVOUS-SYSTEM; C-FOS EXPRESSION; POSTOPERATIVE ILEUS; RECEPTOR SUBTYPES; CENTRAL INJECTION; GROWTH-HORMONE; MESSENGER-RNA; BRAIN; ACTIVATION AB Background Activation of brain somatostatin receptors (sst(1-5)) with the stable pan-sst(1-5) somatostatin agonist, ODT8-SST blocks acute stress and central corticotropin-releasing factor (CRF)-mediated activation of endocrine and adrenal sympathetic responses. Brain CRF signaling is involved in delaying gastric emptying (GE) immediately post surgery. We investigated whether activation of brain sst signaling pathways modulates surgical stress-induced inhibition of gastric emptying and food intake. Methods Fasted rats were injected intracisternally (i.c.) with somatostatin agonists and underwent laparotomy and 1-min cecal palpation. Gastric emptying of a non-nutrient solution and circulating acyl and desacyl ghrelin levels were assessed 50 min post surgery. Food intake was monitored for 24 h. Key Results The abdominal surgeryinduced inhibition of GE (65%), food intake (73% at 2 h) and plasma acyl ghrelin levels (67%) was completely prevented by ODT8-SST (1 mu g per rat, i.c.). The selective sst(5) agonist, BIM-23052 prevented surgeryinduced delayed GE, whereas selective sst(1), sst(2), or sst(4) agonists had no effect. However, the selective sst(2) agonist, S-346-011 (1 mu g per rat, i.c.) counteracted the abdominal surgery-induced inhibition of acyl ghrelin and food intake but not the delayed GE. The ghrelin receptor antagonist, [D-Lys(3)]-GHRP-6 (0.93 mg kg(-1), intraperitoneal, i.p.) blocked i.p. ghrelin-induced increased GE, while not influencing i.c. ODT8-SST-induced prevention of delayed GE and reduced food intake after surgery. Conclusions & Inferences ODT8-SST acts in the brain to prevent surgery-induced delayed GE likely via activating sst(5). ODT8-SST and the sst(2) agonist prevent the abdominal surgeryinduced decrease in food intake and plasma acyl ghrelin indicating dissociation between brain somatostatin signaling involved in preventing surgeryinduced suppression of GE and feeding response. C1 [Stengel, A.; Goebel-Stengel, M.; Wang, L.; Luckey, A.; Hu, E.; Tache, Y.] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress, Dept Med,Digest Dis Div, Los Angeles, CA 90024 USA. [Stengel, A.; Goebel-Stengel, M.; Wang, L.; Luckey, A.; Hu, E.; Tache, Y.] VA Greater Angeles Hlth Care Syst, Los Angeles, CA USA. [Rivier, J.] Salk Inst Biol Studies, Peptide Biol Labs, La Jolla, CA USA. RP Tache, Y (reprint author), VA GLA Healthcare Syst, Ctr Neurobiol Stress, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU Veterans Administration Research Career Scientist Award, VA Merit Award, Center [NIH DK-41301, R01 NIH DK 33061] FX This work was supported by the Veterans Administration Research Career Scientist Award, VA Merit Award, Center Grant NIH DK-41301 (Animal Core) and R01 NIH DK 33061 (YT). JR is the Dr. Frederik Paulsen Chair in Neurosciences Professor. We are grateful to Mrs. Honghui Liang for the excellent technical support. DISCLOSURE NR 75 TC 18 Z9 18 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD JUL PY 2011 VL 23 IS 7 BP E294 EP E308 DI 10.1111/j.1365-2982.2011.01721.x PG 15 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 793OU UT WOS:000292833800004 PM 21569179 ER PT J AU Snapinn, KW Larson, EB Kawakami, H Ujike, H Borenstein, AR Izumi, Y Kaji, R Maruyama, H Mata, IF Morino, H Oda, M Tsuang, DW Yearout, D Edwards, KL Zabetian, CP AF Snapinn, Katherine W. Larson, Eric B. Kawakami, Hideshi Ujike, Hiroshi Borenstein, Amy R. Izumi, Yuishin Kaji, Ryuji Maruyama, Hirofumi Mata, Ignacio F. Morino, Hiroyuki Oda, Masaya Tsuang, Debby W. Yearout, Dora Edwards, Karen L. Zabetian, Cyrus P. TI The UCHL1 S18Y polymorphism and Parkinson's disease in a Japanese population SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; UCHL1; Association study ID UCH-L1 GENE; SUSCEPTIBILITY GENE; ASSOCIATION; VARIANT AB UCHL1 plays an important role in the ubiquitin-proteasome system and is a biologically plausible candidate gene for Parkinson's disease (PD). However, results from genetic association studies of the UCHL1 S18Y polymorphism have been equivocal. Meta-analyses indicate that the polymorphism's risk effect might be restricted to Asian populations and early-onset disease. To further explore the role of UCHL1 in PD, we genotyped S18Y in 605 PD patients and 1620 controls of Japanese ancestry. We did not find evidence of an association in the overall sample (SY vs. SS: adjusted OR=1.11, P=0.37; YY vs. SS: adjusted OR=1.01, P=0.94). In the early-onset stratum, however, we observed a trend toward a reduction in risk for those with the Y allele (SY vs. SS, adjusted OR, 0.75; 95% CI, 0.47-1.20; YY vs. SS, OR, 0.64; 95% CI, 0.36-1.14; trend test, P=0.12). These results indicate that, if involved in PD, the S18Y variant is not a major determinant of risk and its effect might be restricted to early-onset disease. Published by Elsevier Ltd. C1 [Mata, Ignacio F.; Yearout, Dora; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. [Snapinn, Katherine W.; Edwards, Karen L.] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA. [Larson, Eric B.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Larson, Eric B.] Univ Washington, Dept Hlth Serv, Sch Publ Hlth, Seattle, WA 98195 USA. [Kawakami, Hideshi; Maruyama, Hirofumi; Morino, Hiroyuki] Hiroshima Univ, Dept Epidemiol, Res Inst Radiat Biol & Med, Hiroshima, Japan. [Ujike, Hiroshi] Okayama Univ, Dept Neuropsychiat, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008530, Japan. [Borenstein, Amy R.] Univ S Florida, Coll Publ Hlth, Dept Epidemiol & Biostat, Tampa, FL USA. [Izumi, Yuishin; Kaji, Ryuji] Univ Tokushima, Inst Hlth Biosci, Dept Clin Neurosci, Grad Sch, Tokushima 770, Japan. [Mata, Ignacio F.; Yearout, Dora; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Oda, Masaya] Vihara Hananosato Hosp, Dept Neurol, Miyoshi City, Hiroshima, Japan. [Tsuang, Debby W.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Tsuang, Debby W.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, NW Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA 98108 USA. RP Zabetian, CP (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S 182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu RI Maruyama, Hirofumi/B-9333-2011; Kawakami, Hideshi/A-2086-2009; Morino, Hiroyuki/H-9583-2013; Tsuang, Debby/L-7234-2016 OI Kawakami, Hideshi/0000-0002-1405-0901; Morino, Hiroyuki/0000-0002-5190-3547; Tsuang, Debby/0000-0002-4716-1894; Fernandez Mata, Ignacio/0000-0003-1198-0633; Zabetian, Cyrus/0000-0002-7739-4306 FU National Institutes of Health [R01 NS065070, R01 AG009769, P50 NS062684]; Department of Veterans Affairs [1I01BX000531]; Smoking Research Foundation of Japan FX This work was supported by grants from the National Institutes of Health (R01 NS065070, R01 AG009769, and P50 NS062684), Department of Veterans Affairs (1I01BX000531), and the Smoking Research Foundation of Japan. NR 12 TC 9 Z9 10 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD JUL PY 2011 VL 17 IS 6 BP 473 EP 475 DI 10.1016/j.parkreldis.2011.01.019 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 795CG UT WOS:000292948500016 PM 21345711 ER PT J AU Thornburg, K Jonker, S O'Tierney, P Chattergoon, N Louey, S Faber, J Giraud, G AF Thornburg, Kent Jonker, Sonnet O'Tierney, Perrie Chattergoon, Natasha Louey, Samantha Faber, Job Giraud, George TI Regulation of the cardiomyocyte population in the developing heart SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review DE Cardiomyocyte; Fetus; Programming; Terminal differentiation; Atrial natriuretic peptide; Tri-iodo-L-thyronine ID INTRAUTERINE GROWTH RESTRICTION; ATRIAL-NATRIURETIC-FACTOR; CELL-CYCLE ACTIVITY; PLACENTAL EXTRAVILLOUS TROPHOBLASTS; FETAL SHEEP CARDIOMYOCYTES; CARDIAC MYOCYTES; ADULT LIFE; IN-VITRO; VENOUS HYPERTENSION; PRENATAL HYPOXIA AB During fetal life the myocardium expands through replication of cardiomyocytes. In sheep, cardiomyocytes begin the process of becoming terminally differentiated at about 100 gestation days out of 145 days term. In this final step of development, cardiomyocytes become binucleated and stop dividing. The number of cells at birth is important in determining the number of cardiomyocytes for life. Therefore, the regulation of cardiomyocyte growth in the womb is critical to long term disease outcome. Growth factors that stimulate proliferation of fetal cardiomyocytes include angiotensin II, cortisol and insulin-like growth factor-1. Increased ventricular wall stress leads to short term increases in proliferation but longer-term loss of cardiomyocyte generative capacity. Two normally circulating hormones have been identified that suppress proliferation: atrial natriuretic peptide (ANP) and tri-iodo-L-thyronine (T-3). Atrial natriuretic peptide signals through the NPRA receptor that serves as a guanylate cyclase and signals through cGMP. ANP powerfully suppresses mitotic activity in cardiomyocytes in the presence of angiotensin II in culture. Addition of a cGMP analog has the same effect as ANP. ANP suppresses both the extracellular receptor kinases and the phosphoinositol-3 kinase pathways. T-3 also suppresses increased mitotic activity of stimulated cardiomyocytes but does so by increasing the cell cycle suppressant, p21, and decreasing the cell cycle activator, cyclin D1. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Thornburg, Kent; Jonker, Sonnet; O'Tierney, Perrie; Chattergoon, Natasha; Louey, Samantha; Faber, Job; Giraud, George] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97239 USA. [Thornburg, Kent; Jonker, Sonnet; Louey, Samantha; Giraud, George] Oregon Hlth & Sci Univ, Sch Med Cardiovasc Med, Portland, OR 97239 USA. [Giraud, George] Portland VA Med Ctr, Portland, OR 97201 USA. RP Thornburg, K (reprint author), Oregon Hlth & Sci Univ, Heart Res Ctr, 3303 SW Bond,CH15H, Portland, OR 97239 USA. EM thornbur@ohsu.edu OI Thornburg, Kent/0000-0002-5561-4785; Jonker, Sonnet/0000-0002-1097-2562 FU NICHD [P01 HD 34430]; NHLBI [R21 HL093617, R01 HL102763, T32HL094294]; Office of Research on Women's Health; National Institute of Child Health and Human Development; Oregon BIRCWH [HD043488]; M. Lowell Edwards Endowment FX This study was supported by funds from NICHD P01 HD 34430, NHLBI R21 HL093617, and R01 HL102763. Dr. Natasha Chattergoon was supported by NHLBI training grant T32HL094294. Dr. Sonnet Jonker was supported by Office of Research on Women's Health and the National Institute of Child Health and Human Development, Oregon BIRCWH HD043488. Dr. Thornburg was supported by the M. Lowell Edwards Endowment. NR 68 TC 26 Z9 26 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD JUL PY 2011 VL 106 IS 1 SI SI BP 289 EP 299 DI 10.1016/j.pbiomolbio.2010.11.010 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 793XI UT WOS:000292856800004 PM 21147149 ER PT J AU Bean-Mayberry, B Yano, EM Washington, DL Goldzweig, C Batuman, F Huang, C Miake-Lye, I Shekelle, PG AF Bean-Mayberry, Bevanne Yano, Elizabeth M. Washington, Donna L. Goldzweig, Caroline Batuman, Fatma Huang, Christine Miake-Lye, Isomi Shekelle, Paul G. TI Systematic Review of Women Veterans' Health: Update on Successes and Gaps SO WOMENS HEALTH ISSUES LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; QUALITY-OF-LIFE; PRIMARY-CARE CLINICS; UNIVERSITY MEDICAL-CENTERS; OPERATION-IRAQI-FREEDOM; MILITARY SEXUAL TRAUMA; 30-DAY POSTOPERATIVE MORTALITY; RANDOMIZED CONTROLLED-TRIAL; SMOKING-CESSATION PROGRAM; INTIMATE PARTNER VIOLENCE AB Objective: We assessed the state of women veterans' health research by conducting a systematic review of scientific literature published from 2004 to 2008, updating a prior review spanning the history of this literature to 2004. Methods: We identified articles by searching scientific databases and contacting experts. Relevant articles were independently evaluated by two physician reviewers. We categorized 195 articles by study design, funding source, period of military service, research topic, and health condition. Results: More research was published during this 5-year review (n = 195) than in the 25 years beforehand (n = 182). The 195 studies included five trials, but only one randomized trial, a study that examined treatment outcomes for women with posttraumatic stress disorder (PTSD). The large number of articles focused on Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) soldiers' health issues (n = 23) reflects the growing participation of women in these conflicts. High rates of positive PTSD symptoms (range, 10%-19%) and other mental health disorders were found among OEF/OIF returning military women. The recent post-deployment literature underscores the need for repeated PTSD/mental health screening in returning veterans, and points to continuity of care needs for psychiatric and gynecological problems which occur in the field. The psychiatric and access/utilization literature confirmed the positive relationship between military sexual trauma and PTSD and the associated negative health effects. Conclusion: Although most VA women's health research remains observational, methods are evolving toward an analytical focus. Even though successes are evident in the breadth and depth of publications, remaining gaps in the literature include post-deployment readjustment for veterans/families, and quality-of-care interventions/outcomes for physical and mental conditions. Published by Elsevier Inc. C1 [Bean-Mayberry, Bevanne; Yano, Elizabeth M.; Washington, Donna L.; Miake-Lye, Isomi; Shekelle, Paul G.] VA Greater Los Angeles Hlth Serv Res & Dev Ctr Ex, Sepulveda, CA USA. [Bean-Mayberry, Bevanne; Yano, Elizabeth M.; Washington, Donna L.; Goldzweig, Caroline; Batuman, Fatma; Huang, Christine; Miake-Lye, Isomi; Shekelle, Paul G.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Bean-Mayberry, Bevanne; Washington, Donna L.; Goldzweig, Caroline; Batuman, Fatma; Huang, Christine; Shekelle, Paul G.] UCLA David Geffen Sch Med, Dept Med, Los Angeles, CA USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. [Shekelle, Paul G.] W Los Angeles VA Med Ctr, Evidence Synth Program, Los Angeles, CA USA. RP Bean-Mayberry, B (reprint author), VA Sepulveda, VA GLA HSR&D Ctr Study Healthcare Provider Behav, 16111 Plummer St,152, Sepulveda, CA 91343 USA. EM bevanne.bean-mayberry@va.gov RI Schueter, nicos/A-3625-2014 NR 201 TC 58 Z9 58 U1 6 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S84 EP S97 DI 10.1016/j.whi.2011.04.022 PG 14 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100006 PM 21724149 ER PT J AU Dichter, ME Cerulli, C Bossarte, RM AF Dichter, Melissa E. Cerulli, Catherine Bossarte, Robert M. TI Intimate Partner Violence Victimization Among Women Veterans and Associated Heart Health Risks SO WOMENS HEALTH ISSUES LA English DT Article ID SEXUAL-ABUSE; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; SOCIAL SUPPORT; CARE; DEPRESSION; TRAUMA; EXPERIENCES; MECHANISMS; MILITARY AB Purpose: Cardiovascular disease (CVD) is the leading cause of death for women in the United States. CVD risk factors, including depression, smoking, heavy drinking, being overweight, and physical inactivity, are associated with stress and may be linked to women's experiences of intimate partner violence (IPV) victimization. We know little about IPV and CVD risk factors among veteran women. The purpose of this study was to identify the association between lifetime IPV victimization and CVD risk factors among women, accounting for veteran status. Methods: We used data from the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System for 2006 for the eight states that included the IPV module. We explored the associations between veteran status and lifetime IPV victimization and between IPV exposure and CVD risk factors, for veteran and non-veteran women. Findings: Veteran women were more likely than non-veteran women to report lifetime IPV victimization (33.0% vs. 23.8%). IPV exposure was associated with depression, smoking, and heavy drinking. We did not find evidence for an association between IPV exposure and lack of exercise or being overweight or obese, when controlling for demographic characteristics and veteran status. Conclusion: Women veterans have particularly high rates of lifetime IPV victimization. In addition, IPV victimization is associated with an increased risk of heart health risk factors. The findings suggest that we should attend to IPV exposure among veteran women and further investigate the link between IPV and military service, and the associated health impacts. Published by Elsevier Inc. C1 [Dichter, Melissa E.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Cerulli, Catherine] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Bossarte, Robert M.] Canandaigua VA Med Ctr, VISN Ctr Excellence 2, Canandaigua, NY USA. RP Dichter, ME (reprint author), Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, 3900 Woodland Ave,Bldg 4100, Philadelphia, PA 19104 USA. EM mdichter@sp2.upenn.edu NR 40 TC 31 Z9 31 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S190 EP S194 DI 10.1016/j.whi.2011.04.008 PG 5 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100019 PM 21724140 ER PT J AU Farmer, MM Rose, DE Riopelle, D Lanto, AB Yano, EM AF Farmer, Melissa M. Rose, Danielle E. Riopelle, Deborah Lanto, Andy B. Yano, Elizabeth M. TI Gender Differences in Smoking and Smoking Cessation Treatment: An Examination of the Organizational Features Related to Care SO WOMENS HEALTH ISSUES LA English DT Article ID QUALITY-OF-CARE; WOMEN VETERANS; UNITED-STATES; MANAGED CARE; DISPARITIES; DEPRESSION; ABSTINENCE; SERVICES; PROGRAM; RECALL AB Objectives: Veterans experience a particularly heavy burden with smoking rates higher than the general population, and the smoking prevalence for women Veterans has increased in recent years. We examined differences in smoking prevalence and treatment by gender for Veterans receiving at least some of their care at a VA facility, and examined the degree to which organizational factors may be associated with reductions in gender disparities in smoking cessation treatment. Methods: We merged national organizational-level data focused on primary care (sites = 225) and women's health (sites = 195) with patient-level survey data (n = 15,033 smokers). Organizational measures focused on smoking cessation-specific structure and processes in primary care and women's health. Primary outcomes were patient-reported receipt of smoking cessation treatments advised to quit, medication recommendation, and other treatment recommendation. We used multi-level, random-intercept logistic regression. Results: In 2007, 29% of women and 23% of men were smokers. Overall, 83% of smokers reported they had been advised to quit, 62% recommended medications, and 60% recommended other treatments. Women were more likely to report being advised to quit (odds ratio, 1.33; 95% confidence interval, 1.07-1.64) but equally likely as men to have medications or other treatment recommended. Organizational factors did not eliminate the gender differences in being advised to quit. Conclusion: Despite having equivalent or higher smoking cessation treatment rates, women Veterans were more likely to smoke than men. With the rapid growth of women entering VA care, the need for effective gender-focused and gender-sensitive smoking cessation care arrangements is critical for the future health of women who have served. Published by Elsevier Inc. C1 [Farmer, Melissa M.; Rose, Danielle E.; Riopelle, Deborah; Lanto, Andy B.; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, HSR&D, VA Hlth Serv Res & Dev Ctr Excellence, Sepulveda, CA 91343 USA. [Farmer, Melissa M.; Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. RP Farmer, MM (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, HSR&D, VA Hlth Serv Res & Dev Ctr Excellence, 16111 Plummer St,152, Sepulveda, CA 91343 USA. EM Melissa.Farmer@va.gov NR 41 TC 18 Z9 18 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S182 EP S189 DI 10.1016/j.whi.2011.04.018 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100018 PM 21724139 ER PT J AU Lipson, L Eisen, S AF Lipson, Linda Eisen, Seth TI VA Research: Committed to Women Who Have "Borne the Battle" and Beyond SO WOMENS HEALTH ISSUES LA English DT Editorial Material ID HEALTH-CARE; VETERANS; QUALITY C1 [Lipson, Linda; Eisen, Seth] Hlth Serv Res & Dev Serv, US Dept Vet Affairs, Washington, DC USA. RP Lipson, L (reprint author), Hlth Serv Res & Dev Serv, Dept Vet Affairs, Mail Code 124,810 Vermont Ave NW, Washington, DC 20420 USA. EM Linda.Lipson@va.gov NR 12 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S67 EP S69 DI 10.1016/j.whi.2011.04.026 PG 3 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100003 PM 21724146 ER PT J AU MacGregor, C Hamilton, AB Oishi, SM Yano, EM AF MacGregor, Casey Hamilton, Alison B. Oishi, Sabine M. Yano, Elizabeth M. TI Description, Development, and Philosophies of Mental Health Service Delivery for Female Veterans in the VA: A Qualitative Study SO WOMENS HEALTH ISSUES LA English DT Article ID WOMEN VETERANS; PRIMARY-CARE; GENDER-DIFFERENCES; AFGHANISTAN; CLINICS; IRAQ; INNOVATION; TRAUMA AB Purpose: National Veterans Health Administration (VA) organizational data suggested the presence of separate and formal mental health services for female veterans, prompting qualitative exploration of their structure and development. Methods: Semistructured telephone interviews were conducted with a purposeful sample of 36 VA mental health administrators and providers from 26 VA Medical Centers and large community-based outpatient clinics that reported having separate women's mental health clinics and/or designated women's mental health providers in their outpatient mental health clinics. Main Findings: VA facilities have implemented a spectrum of women's mental health service delivery arrangements, including specialized mental health providers, co-located mental health providers in women's health clinics, women-only mental health groups, and women's mental health clinics. Most facilities had one or more "champions" developing such services, but some faced challenges in maintaining viability. Some respondents expressed concern about possible stigmatization associated with creating separate mental health services for female veterans. Conclusion: Arrangements of VA mental health services for female veterans vary across facilities. This study identified a lack of consensus in the field regarding the need for and consequences of adapting existing programs specifically for the mental health needs of female veterans. Implementation of VA policy may require greater attention to frontline providers' perspectives. Comparative impact studies of female veterans' mental health service delivery arrangements are also needed. Published by Elsevier Inc. C1 [MacGregor, Casey] VA Greater Los Angeles Healthcare Syst, QUERI Ctr Implementat Practice & Res Support CIPR, VA HSR&D Ctr Excellence Study Healthcare Provider, Sepulveda, CA 91343 USA. [Hamilton, Alison B.] VA Greater Los Angeles Healthcare Syst, Desert Pacific Mental Illness Res Educ & Clin Ctr, Los Angeles, CA USA. [Hamilton, Alison B.] Univ Calif Los Angeles, Sch Med, Dept Psychiat, Integrated Substance Abuse Programs, Los Angeles, CA 90024 USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. RP MacGregor, C (reprint author), VA Greater Los Angeles Healthcare Syst, QUERI Ctr Implementat Practice & Res Support CIPR, VA HSR&D Ctr Excellence Study Healthcare Provider, 16111 Plummer St,152, Sepulveda, CA 91343 USA. EM Casey.Macgregor@va.gov NR 22 TC 10 Z9 10 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S138 EP S144 DI 10.1016/j.whi.2011.04.006 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100012 PM 21724133 ER PT J AU Oishi, SM Rose, DE Washington, DL MacGregor, C Bean-Mayberry, B Yano, EM AF Oishi, Sabine M. Rose, Danielle E. Washington, Donna L. MacGregor, Casey Bean-Mayberry, Bevanne Yano, Elizabeth M. TI National Variations in VA Mental Health Care for Women Veterans SO WOMENS HEALTH ISSUES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; FEMALE VETERANS; SEXUAL TRAUMA; GENDER; ENVIRONMENT; IMPROVEMENT; DEPRESSION; PREVALENCE; ANXIETY; ABUSE AB Objectives: Although the Veterans Health Administration (VA) has recently adopted new policies encouraging gender-specific mental health (MH) care delivery to women veterans, little is known about the potential difficulties local facilities may face in achieving compliance. We assessed variations in women's mental health care delivery arrangements in VA facilities nationwide. Methods: We used results from the VA Survey of Women Veterans Health Programs, a key informant survey of senior women's health clinicians representing all VA facilities serving more than 300 women veterans, to assess the array of gender-sensitive mental health care arrangements (response rate, 86%; n = 195). We also examined organizational and area factors related to availability of women's specialty mental health arrangements using multivariable logistic regression. Results: Nationally, over half (53%) of VA facilities had some form of gender-sensitive mental health care arrangements. Overall, 34% of sites reported having designated women's mental health providers in general outpatient mental health clinics (MHCs). Almost half (48%) had therapy groups for women in their MHCs. VAs with women's primary care clinics also delivered mental health services (24%), and 12% of VAs reported having a separate women's MHC, most of which (88%) offered sexual trauma group counseling. Assignment to same-gender mental health providers is not routine. VAs with comprehensive women's primary care clinics were more likely to integrate mental health care for women as well. Conclusion: Local implementation of gender-sensitive mental health care in VA settings is highly variable. Although this variation may reflect diverse local needs and resources, women veterans may also sometimes face challenges in accessing needed services. Published by Elsevier Inc. C1 [Oishi, Sabine M.; Rose, Danielle E.; Washington, Donna L.; MacGregor, Casey; Bean-Mayberry, Bevanne; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Excellence Study Healthcare Provider, Sepulveda, CA 91343 USA. [Washington, Donna L.; Bean-Mayberry, Bevanne] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Washington, Donna L.; Bean-Mayberry, Bevanne] UCLA Sch Med, Los Angeles, CA USA. [MacGregor, Casey] QUERI Ctr Implementat Practice & Res Support CIPR, Los Angeles, CA USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. RP Oishi, SM (reprint author), VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Excellence Study Healthcare Provider, 16111 Plummer St,152, Sepulveda, CA 91343 USA. EM sabine.oishi@va.gov NR 30 TC 17 Z9 17 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S130 EP S137 DI 10.1016/j.whi.2011.04.029 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100011 PM 21724132 ER PT J AU Sternke, LM AF Sternke, Lisa Marie TI Measurement of Military Combat Exposure Among Women: Analysis and Implications SO WOMENS HEALTH ISSUES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH PROBLEMS; FEMALE VIETNAM VETERANS; GENDER-DIFFERENCES; TRAUMA EXPOSURE; WAR VETERANS; LONGITUDINAL ASSESSMENT; FUNCTIONAL HEALTH; ABUSIVE VIOLENCE; PHYSICAL HEALTH AB Purpose: To examine combat exposure measurement instruments utilized since the Vietnam War, determine how these instruments were developed and psychometrically tested, and if they are appropriate for use with women veterans exposed to combat. Methods: A literature search for articles concerning combat exposure instruments, their development, and their psychometric properties in relation to women was conducted in several electronic databases. Limited MeSH subject headings required keyword searches with terms such as combat stress, war trauma, and deployment stressors. Instruments were selected for analysis based on their inclusion of combat and combat-related traumatic event measures. Results: Eight instruments were retained for critical appraisal. The majority of instruments were developed and validated based on male veterans' combat experiences from the Vietnam War through the Gulf War. Located instruments explained their methodological development and indicated the type of exposure being measured. Reliability measures for the majority were acceptable, and validity was established to varying degrees and with different methods. Limitations of all instruments included retrospective self-reporting, potential recall error, and the inability to validate individual exposure objectively. Conclusion: Women veterans are substantially under-represented in the development and psychometric testing of combat exposure instruments, indicating a male gender bias in most combat measures. Only two instruments utilized women veterans in their validation samples, and six instruments used gender-neutral terminology. Instruments developed and validated with male veterans for specific military conflicts may not reflect the combat experiences of women. Published by Elsevier Inc. C1 [Sternke, Lisa Marie] Ralph H Johnson VA Med Ctr, VA Nursing Acad, Dept Vet Affairs, Charleston, SC USA. [Sternke, Lisa Marie] Med Univ S Carolina, Coll Nursing, Charleston, SC USA. RP Sternke, LM (reprint author), 109 Bee St, Charleston, SC 29401 USA. EM Lisa.Sternke@va.gov NR 84 TC 7 Z9 7 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S160 EP S168 DI 10.1016/j.whi.2011.04.020 PG 9 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100015 PM 21724136 ER PT J AU Washington, DL Bean-Mayberry, B Mitchell, MN Riopelle, D Yano, EM AF Washington, Donna L. Bean-Mayberry, Bevanne Mitchell, Michael N. Riopelle, Deborah Yano, Elizabeth M. TI Tailoring VA Primary Care to Women Veterans: Association with Patient-Rated Quality and Satisfaction SO WOMENS HEALTH ISSUES LA English DT Article ID AFFAIRS MEDICAL-CENTER; HEALTH-CARE; NATIONAL-CENTERS; AVAILABILITY; CLINICS; DELIVERY; EXCELLENCE; INNOVATION; SERVICES AB Background: Primary care delivery models tailored to women's needs and preferences are associated with higher quality and satisfaction. Therefore, the U.S. Department of Veterans Affairs (VA) recommends adoption of designated providers for women in primary care clinics or women's health centers as the optimal models for women's primary care. We assessed women veterans' ratings of their VA health care quality, gender-related satisfaction, gender appropriateness, and VA provider skills in treating women, in relation to primary care model at VA sites nationwide. Methods: Health care ratings were obtained from VA users in the 2008-2009 National Survey of Women Veterans. VA administrative data identified the site for each respondent's primary care. Facility data identified the site's primary care model for women. We conducted multilevel modeling to compare health care ratings for sites serving 300 or more women veterans who had adopted VA recommendations for women's primary care models (adopter sites), with non-adopter sites, and with small sites serving fewer women veterans, adjusting for patient characteristics. Results: Adopter sites received higher adjusted ratings of gender-related satisfaction and perceptions of VA provider skills than non-adopter and small sites. Adopter sites also received higher adjusted ratings of gender appropriateness than small sites. Adjusted ratings of quality of care did not differ by type of site. Conclusion: VA sites with primary care models tailored to women were rated higher on most dimensions of care. Facilitating establishment of these optimal care models at other sites is one strategy for improving women veterans' experiences with VA care. Research to identify other features of care associated with quality could inform ongoing VA quality transformation efforts. Published by Elsevier Inc. C1 [Washington, Donna L.; Bean-Mayberry, Bevanne; Mitchell, Michael N.; Riopelle, Deborah; Yano, Elizabeth M.] VA Greater Los Angeles Hlth Serv Res & Dev HSR&D, Ctr Excellence, Sepulveda, CA USA. [Washington, Donna L.; Bean-Mayberry, Bevanne] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM donna.washington@va.gov NR 32 TC 20 Z9 20 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S112 EP S119 DI 10.1016/j.whi.2011.04.004 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100009 PM 21724130 ER PT J AU Yano, EM Bastian, LA Bean-Mayberry, B Eisen, S Frayne, S Hayes, P Klap, R Lipson, L Mattocks, K McGlynn, G Sadler, A Schnurr, P Washington, DL AF Yano, Elizabeth M. Bastian, Lori A. Bean-Mayberry, Bevanne Eisen, Seth Frayne, Susan Hayes, Patricia Klap, Ruth Lipson, Linda Mattocks, Kristin McGlynn, Geraldine Sadler, Anne Schnurr, Paula Washington, Donna L. TI Using Research to Transform Care for Women Veterans: Advancing the Research Agenda and Enhancing Research-Clinical Partnerships SO WOMENS HEALTH ISSUES LA English DT Article ID AFFAIRS HEALTH-CARE; INSTITUTES-OF-HEALTH; PATIENT SATISFACTION; QUALITY; SYSTEM; GENDER; FEMALE AB The purpose of this paper is to report on the outcomes of the 2010 VA Women's Health Services Research Conference, which brought together investigators interested in pursuing research on women veterans and women in the military with leaders in women's health care delivery and policy within and outside the VA, to significantly advance the state and future direction of VA women's health research and its potential impacts on practice and policy. Building on priorities assembled in the previous VA research agenda (2004) and the research conducted in the intervening six years, we used an array of approaches to foster research-clinical partnerships that integrated the state-of-the-science with the informational and strategic needs of senior policy and practice leaders. With demonstrated leadership commitment and support, broad field-based participation, strong interagency collaboration and a push to accelerate the move from observational to interventional and implementation research, the Conference provided a vital venue for establishing the foundation for a new research agenda. In this paper, we provide the historical evolution of the emergence of women veterans' health services research and an overview of the research in the intervening years since the first VA women's health research agenda. We then present the resulting VA Women's Health Research Agenda priorities and supporting activities designed to transform care for women veterans in six broad areas of study, including access to care and rural health; primary care and prevention; mental health; post deployment health; complex chronic conditions, aging and long-term care; and reproductive health. Published by Elsevier Inc. C1 [Yano, Elizabeth M.; Bean-Mayberry, Bevanne; Klap, Ruth; Washington, Donna L.] VA Greater Los Angeles HSR&D Ctr Excellence, Study Healthcare Provider Behav, Los Angeles, CA USA. [Yano, Elizabeth M.; Klap, Ruth] VA Greater Los Angeles Healthcare Syst, VA Womens Hlth Res Consortium, Sepulveda, CA USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. [Yano, Elizabeth M.; Bastian, Lori A.; Bean-Mayberry, Bevanne; Frayne, Susan] Women Vet Practice Based Res Network, Iowa City, IA USA. [Bastian, Lori A.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Bastian, Lori A.] Duke Univ, Med Ctr, Div Gen Internal Med, Durham, NC 27710 USA. [Bean-Mayberry, Bevanne] VA Greater Los Angeles Healthcare Syst, Comprehens Womens Hlth Ctr, Sepulveda, CA USA. [Bean-Mayberry, Bevanne; Washington, Donna L.] VA Greater Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA USA. [Bean-Mayberry, Bevanne; Washington, Donna L.] UCLA Sch Med, Los Angeles, CA USA. [Eisen, Seth; Lipson, Linda] Vet Hlth Adm, VA HSR&D Serv, VA Cent Off, Washington, DC USA. [Frayne, Susan] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA. [Frayne, Susan] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Hayes, Patricia] Vet Hlth Adm, Women Vet Hlth Strateg Hlth Care Grp, Off Patient Care Serv, Washington, DC USA. [Mattocks, Kristin] W Haven VA Med Ctr, West Haven, CT USA. [Mattocks, Kristin] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [McGlynn, Geraldine] Ctr Informat Disseminat & Educ Resources, Boston, MA USA. [Sadler, Anne] Iowa City VA, CRIISP, Iowa City, IA USA. [Sadler, Anne] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA. [Schnurr, Paula] White River Junct VA Med Ctr, Natl Ctr Posttraumat Stress Disorder PTSD, White River Jct, VT USA. [Schnurr, Paula] Dartmouth Coll, Dept Psychiat, Hanover, NH USA. [Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, Comprehens Womens Hlth Ctr, Los Angeles, CA USA. RP Yano, EM (reprint author), VA Greater Los Angeles HSR&D Ctr Excellence, 16111 Plummer St,Mailcode 152, Sepulveda, CA 91343 USA. EM elizabeth.yano@va.gov NR 41 TC 29 Z9 29 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S73 EP S83 DI 10.1016/j.whi.2011.04.002 PG 11 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100005 PM 21724148 ER PT J AU Yano, EM Frayne, SM AF Yano, Elizabeth M. Frayne, Susan M. TI Health and Health Care of Women Veterans and Women in the Military: Research Informing Evidence-Based Practice and Policy SO WOMENS HEALTH ISSUES LA English DT Editorial Material C1 [Yano, Elizabeth M.; Frayne, Susan M.] VA Womens Hlth Res Network, Los Angeles, CA USA. [Yano, Elizabeth M.; Frayne, Susan M.] VA Womens Hlth Res Network, Palo Alto, CA USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. [Frayne, Susan M.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA. [Frayne, Susan M.] Stanford Univ, Div Gen Med Disciplines, Stanford, CA 94305 USA. [Yano, Elizabeth M.] VA Greater Los Angeles HSR&D Ctr Excellence, Study Healthcare Provider Behav, Sepulveda, CA 91343 USA. RP Yano, EM (reprint author), VA Greater Los Angeles HSR&D Ctr Excellence, Study Healthcare Provider Behav, 16111 Plummer St,Mailcode 152, Sepulveda, CA 91343 USA. EM elizabeth.yano@va.gov NR 8 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S64 EP S66 DI 10.1016/j.whi.2011.04.030 PG 3 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100002 PM 21724145 ER PT J AU Yee, EFT White, R Lee, SJ Washington, DL Yano, EM Murata, G Handanos, C Hoffman, RM AF Yee, Ellen F. T. White, Robert Lee, Sang-Joon Washington, Donna L. Yano, Elizabeth M. Murata, Glen Handanos, Christine Hoffman, Richard M. TI Mental Illness: Is there an Association With Cancer Screening Among Women Veterans? SO WOMENS HEALTH ISSUES LA English DT Article ID INTEGRATED MEDICAL-CARE; COLORECTAL-CANCER; HEALTH-CARE; CERVICAL-CANCER; UNITED-STATES; PREVENTIVE SERVICES; BREAST; QUALITY; ACCESS; MAMMOGRAPHY AB Purpose: Mental illness may be a barrier to achieving timely and appropriate cancer screening. We evaluated the association of mental illness with receipt of and adherence to breast, cervical, and colorectal cancer screening among women Veterans. Methods: The study population included all female Veterans ages 50 to 65 who obtained care at the New Mexico VA Health Care System continuously from fiscal years 2004 to 2006 (n = 606). Measures were odds ratios (OR) for receipt of any cancer screening, and adherence to recommended cancer screening frequency, adjusted for age, insurance, service connection, and primary care and women's clinic visits. Results: Overall, 53% of the women had a mental health diagnosis (MHD). Women with an MHD were less likely to adhere to recommended breast cancer screening than women without MHD: unadjusted OR (95% CI): 0.73 (0.54-0.98; p < .05), adjusted OR (aOR) (95% CI) 0.60 (0.44-0.82; p < .01). Women with an MHD were as likely as women without MHD to receive any breast, cervical, and colon cancer screening; Respective aORs (95% CI): 0.79 (0.50-1.25); 1.71 (0.91-3.21); and 0.85 (0.56-1.28). Conclusion: Women with a mental illness are at risk for not adhering to recommended routine breast cancer screening, and may require more intensive efforts to achieve optimal rates of recommended breast cancer screening. Published by Elsevier Inc. C1 [Yee, Ellen F. T.; Murata, Glen; Hoffman, Richard M.] Univ New Mexico, Sch Med, Dept Med, New Mexico VA Hlth Care Syst, Albuquerque, NM 87131 USA. [White, Robert] ABQ Hlth Partners, Albuquerque, NM USA. [Lee, Sang-Joon] Univ New Mexico, Sch Med, Dept Internal Med, Albuquerque, NM 87131 USA. [Washington, Donna L.; Yano, Elizabeth M.] VA Greater Angeles Hlth Serv Res & Dev, Ctr Excellence, Sepulveda, CA USA. [Washington, Donna L.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. [Handanos, Christine] So Maine Med Ctr, Biddeford, ME USA. RP Yee, EFT (reprint author), New Mexico VA Hlth Care, 1501 San Pedro Dr SE,MC 111, Albuquerque, NM 87108 USA. EM Ellen.yee2@va.gov NR 57 TC 14 Z9 14 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2011 VL 21 IS 4 SU S SI SI BP S195 EP S202 DI 10.1016/j.whi.2011.04.027 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 792YA UT WOS:000292785100020 PM 21724141 ER PT J AU Granholm, E Tate, SR Link, PC Lydecker, KP Cummins, KM McQuaid, J Shriver, C Brown, SA AF Granholm, Eric Tate, Susan R. Link, Peter C. Lydecker, Katherine P. Cummins, Kevin M. McQuaid, John Shriver, Chris Brown, Sandra A. TI Neuropsychological Functioning and Outcomes of Treatment for Co-occurring Depression and Substance Use Disorders SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE depression; substance use disorders; cognitive behavioral therapy; neuropsychological impairment ID COGNITIVE IMPAIRMENT; ALCOHOL-USE; 12-STEP FACILITATION; DEPENDENT ADULTS; MAJOR DEPRESSION; DRUG-USE; COMORBIDITY; DRINKING; REPLICATION; MECHANISMS AB Background: We previously published findings from our clinical trial comparing treatment outcomes for substance-dependent veterans with co-occurring depression who received Integrated Cognitive Behavioral Therapy (ICBT) or Twelve-Step Facilitation (TSF) Therapy. Objectives: This study is a secondary analysis that examined whether neuropsychological functioning at baseline moderated substance use and depression outcomes in ICBT relative to TSF. Methods: This study was a randomized clinical trial in which 164 veterans with major depressive disorder and comorbid alcohol, cannabinol, and/or stimulant dependence were randomly assigned to either ICBT or TSF group therapy. A comprehensive neuropsychological test battery was administered at baseline. Results: Contrary to our hypothesis, participants with poor neuropsychological functioning had better substance use outcome in ICBT than in TSF, whereas participants with good neuropsychological functioning had comparable substance use outcomes in TSF and ICBT by 18-month follow-up. Depression outcomes, in contrast, were not moderated by neuropsychological functioning by 18-month follow-up. Conclusions and Scientific Significance: The substance use outcomes may suggest that substance-dependent depressed adults with poorer neuropsychological functioning should be offered ICBT over TSF. These individuals may be less able to develop and use novel coping skills for managing substance use and depressive symptoms on their own without formal structured training in cognitive and behavioral skills provided in ICBT. C1 [Granholm, Eric; Tate, Susan R.; Link, Peter C.] VA San Diego Healthcare Syst, San Diego, CA 92161 USA. [Granholm, Eric; Tate, Susan R.; Cummins, Kevin M.; Brown, Sandra A.] Univ Calif San Diego, Dept Psychol, San Diego, CA 92161 USA. [Lydecker, Katherine P.] San Diego State Univ, San Diego Joint Doctoral Program Clin Psychol, San Diego, CA 92182 USA. [McQuaid, John] San Francisco VA Med Ctr, San Francisco, CA USA. [McQuaid, John] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shriver, Chris] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92161 USA. RP Tate, SR (reprint author), VA San Diego Healthcare Syst, 3350 La Jolla Village Dr 116B, San Diego, CA 92161 USA. EM srtate@ucsd.edu RI Granholm, Eric/P-7680-2014 NR 45 TC 4 Z9 4 U1 1 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD JUL PY 2011 VL 37 IS 4 BP 240 EP 249 DI 10.3109/00952990.2011.570829 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 791VO UT WOS:000292695600006 PM 21517712 ER PT J AU Day, LW Walter, LC Velayos, F AF Day, Lukejohn W. Walter, Louise C. Velayos, Fernando TI Colorectal Cancer Screening and Surveillance in the Elderly Patient SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID ORAL SODIUM-PHOSPHATE; ELECTROLYTE LAVAGE SOLUTION; SERVICES TASK-FORCE; SINGLE-BLIND TRIAL; AGED 80 YEARS; POLYETHYLENE-GLYCOL; BOWEL PREPARATION; COLONOSCOPIC PERFORATIONS; CURATIVE RESECTION; RADICAL SURGERY AB Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Older age is associated with a rise in colorectal cancer and adenomas, necessitating the need for CRC screening in older patients. However, decisions about CRC screening and surveillance in older adults are often difficult and challenging. The decision requires an individualized assessment that incorporates factors unique to performing colonoscopy in older adults in order to weigh the risks and benefits for each patient according to their overall health and preferences. This review addresses the factors unique to colorectal cancer and performing colonoscopy in older adults that are relevant in weighing the risks and benefits of screening and surveillance in this population. C1 [Day, Lukejohn W.] San Francisco Gen Hosp, Div Gastroenterol, San Francisco, CA 94110 USA. [Day, Lukejohn W.] Univ Calif San Francisco, Dept Med, GI Hlth Outcomes Policy & Econ HOPE Res Program, San Francisco, CA USA. [Walter, Louise C.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Velayos, Fernando] Univ Calif San Francisco, Dept Med, Div Gastroenterol, San Francisco, CA USA. RP Day, LW (reprint author), San Francisco Gen Hosp, Div Gastroenterol, 1001 Potrero Ave,3D-5, San Francisco, CA 94110 USA. EM lukejohn.day@ucsf.edu FU NIH UCSF-CTSI [KL2 RR024130]; VA Health Services Research and Development [IIR-04-427]; National Cancer Institute [1R01CA134425] FX F.V. was supported in part by NIH UCSF-CTSI Grant number KL2 RR024130. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. L. C. W. was supported by a VA Health Services Research and Development Grant IIR-04-427 and by Grant 1R01CA134425 from the National Cancer Institute. NR 117 TC 19 Z9 21 U1 0 U2 6 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 JUL PY 2011 VL 106 IS 7 BP 1197 EP 1206 DI 10.1038/ajg.2011.128 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 789JG UT WOS:000292511100004 PM 21519362 ER PT J AU Sproul, A Steele, SL Thai, TL Yu, SP Klein, JD Sands, JM Bell, PD AF Sproul, Adrian Steele, Stacy L. Thai, Tiffany L. Yu, ShanPing Klein, Janet D. Sands, Jeff M. Bell, P. Darwin TI N-methyl-D-aspartate receptor subunit NR3a expression and function in principal cells of the collecting duct SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE cytosolic calcium; aquaporin 2; medullary tonicity ID NR3A-CONTAINING NMDA RECEPTORS; PROTEIN PHOSPHATASE 2A; NONMUSCLE MYOSIN-II; RAT-KIDNEY; DEVELOPMENTAL REGULATION; DIABETES-INSIPIDUS; UP-REGULATION; MICE LACKING; VASOPRESSIN; IDENTIFICATION AB Sproul A, Steele SL, Thai TL, Yu S, Klein JD, Sands JM, Bell PD. N-methyl-D-aspartate receptor subunit NR3a expression and function in principal cells of the collecting duct. Am J Physiol Renal Physiol 301: F44-F54, 2011. First published March 23, 2011; doi: 10.1152/ajprenal.00666.2010.-N-methyl-D-aspartate receptors (NMDARs) are Ca(2+) -permeable, ligand-gated, nonselective cation channels that function as neuronal synaptic receptors but which are also expressed in multiple peripheral tissues. Here, we show for the first time that NMDAR subunits NR3a and NR3b are highly expressed in the neonatal kidney and that there is continued expression of NR3a in the renal medulla and papilla of the adult mouse. NR3a was also expressed in mIMCD-3 cells, where it was found that hypoxia and hypertonicity upregulated NR3a expression. Using short-hairpin (sh) RNA-based knockdown, a stable inner medullary collecting duct (IMCD) cell line was established that had similar to 80% decrease in NR3a. Knockdown cells exhibited an increased basal intracellular calcium concentration, reduced cell proliferation, and increased cell death. In addition, NR3a knockdown cells exhibited reduced water transport in response to the addition of vasopressin, suggesting an alteration in aquaporin-2 (AQP2) expression/function. Consistent with this notion, we demonstrate decreased surface expression of glycosylated AQP2 in IMCD cells transfected with NR3a shRNA. To determine whether this also occurred in vivo, we compared AQP2 levels in wild-type vs. in NR3a(-/-) mice. Total AQP2 protein levels in the outer and inner medulla were significantly reduced in knockout mice compared with control mice. Finally, NR3a(-/-) mice showed a significant delay in their ability to increase urine osmolality during water restriction. Thus NR3a may play a renoprotective role in collecting duct cells. Therefore, under conditions that are associated with high vasopressin levels, NR3a, by maintaining low intracellular calcium levels, protects the function of the principal cells to reabsorb water and thereby increase medullary osmolality. C1 [Sproul, Adrian; Steele, Stacy L.; Bell, P. Darwin] Med Univ S Carolina, Dept Med, Charleston, SC 29403 USA. [Steele, Stacy L.; Bell, P. Darwin] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Thai, Tiffany L.; Klein, Janet D.; Sands, Jeff M.] Emory Univ, Dept Med, Atlanta, GA 30322 USA. [Yu, ShanPing] Emory Univ, Dept Anesthesiol, Atlanta, GA 30322 USA. RP Bell, PD (reprint author), Med Univ S Carolina, Dept Med, 173 Ashley Ave,210 CRI, Charleston, SC 29403 USA. EM Bellpd@musc.edu FU Veterans Affairs Merit Award; National Institutes of Health (NIH) [DK32032, P30 DK074038]; National Center for Research Resources FX This work was supported by a Veterans Affairs Merit Award (P. D. Bell) and National Institutes of Health (NIH) Grants DK32032 (P. D. Bell) and P30 DK074038 (P. D. Bell; UAB Core Center, Lisa Guay-Woodford, PI). This work was conducted in a facility constructed with NIH support (Grant C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources). NR 49 TC 14 Z9 14 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL PY 2011 VL 301 IS 1 BP F44 EP F54 DI 10.1152/ajprenal.00666.2010 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 791CY UT WOS:000292641000009 PM 21429969 ER PT J AU Weintraub, D Chen, PJ Ignacio, RV Mamikonyan, E Kales, HC AF Weintraub, Daniel Chen, Peijun Ignacio, Rosalinda V. Mamikonyan, Eugenia Kales, Helen C. TI Patterns and Trends in Antipsychotic Prescribing for Parkinson Disease Psychosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID DRUG-INDUCED PSYCHOSIS; NURSING-HOME PLACEMENT; ATYPICAL ANTIPSYCHOTICS; ELDERLY USERS; OLDER-ADULTS; DOUBLE-BLIND; LEWY BODIES; DEMENTIA; RISK; POPULATION AB Background: Antipsychotic (AP) use is common in Parkinson disease (PD), but APs can worsen parkinsonism, evidence for efficacy is limited, and use in patients with dementia increases mortality. Objective: To examine the frequency and characteristics, including changes over time, of AP use in a large cohort of patients with PD. Design: Using Veterans Affairs data from fiscal year (FY) 2008, rates and predictors of AP prescribing were determined for patients with PD and psychosis stratified by dementia status (N = 2597) and a comparison group of patients with dementia and psychosis without PD (N = 6907). Fiscal year 2008 and FY2002 data were compared to examine changes in AP prescribing over time. Setting: Department of Veterans Affairs outpatient facilities. Participants: Outpatients with PD and psychosis and outpatients without PD with dementia and psychosis, all receiving care at Veterans Affairs facilities in FY2002 and FY2008. Main Outcome Measure: Antipsychotic prescribing, including overall, class, and specific medications. Results: In FY2008, 50% of patients with PD having a diagnosis of psychosis were prescribed an AP. Among treated patients, the atypical AP quetiapine was most frequently prescribed (66%), but approximately 30% received high-potency APs. Clozapine was rarely prescribed (<2%). In multivariate models, diagnoses of PD and dementia were associated with AP use. Comparing FY2008 with FY2002, AP use in PD was unchanged, with decreases in risperidone and olanzapine use offset by an increase in quetiapine prescribing and the introduction of aripiprazole. Conclusions: Half of the patients with PD and psychosis receive APs, not uncommonly high-potency agents associated with worsening parkinsonism, and frequency of use has been unchanged since the "black box" warning for AP use in patients with dementia was issued. Recent trends are a shift to quetiapine use and the common use of aripiprazole. As psychosis and dementia are frequently comorbid in PD, safety risks associated with AP use in this population need to be assessed. C1 [Weintraub, Daniel; Mamikonyan, Eugenia] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Chen, Peijun] Cleveland Vet Affairs Med Ctr, Psychiat Serv, Cleveland, OH USA. [Chen, Peijun] Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. [Ignacio, Rosalinda V.; Kales, Helen C.] Univ Michigan, Natl Vet Affairs Serious Mental Illness Treatment, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48109 USA. [Ignacio, Rosalinda V.; Kales, Helen C.] Univ Michigan, Mental Hlth Serv Outcomes & Translat Sect, Ann Arbor, MI 48109 USA. [Kales, Helen C.] Univ Michigan, Dept Psychiat, Geriatr Psychiat Sect, Ann Arbor, MI 48109 USA. RP Weintraub, D (reprint author), Univ Penn, Dept Psychiat, 3615 Chestnut St,Room 330, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU National Institute of Mental Health [K23 MH067894, R01 MH081070] FX This research was supported by grants K23 MH067894 (Dr Weintraub) and R01 MH081070 (Dr Kales) from the National Institute of Mental Health. Online-Only Material: The eTable is available at http://www.archneurol.com. NR 41 TC 42 Z9 42 U1 1 U2 6 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 JUL PY 2011 VL 68 IS 7 BP 899 EP 904 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 790QG UT WOS:000292603700008 PM 21747029 ER PT J AU Schlosser, RJ Harvey, RJ AF Schlosser, Rodney J. Harvey, Richard J. TI Untitled SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID ENDOSCOPIC SINUS SURGERY; EDUCATIONAL INTERVENTION; CHRONIC RHINOSINUSITIS; PARANASAL SINUSES; FACIAL GROWTH; CHILDREN; ADENOIDECTOMY; MANAGEMENT; EFFICACY; BIOFILMS C1 [Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Harvey, Richard J.] St Vincents Hosp, Dept Otolaryngol & Skull Base Surg, Sydney, NSW 2010, Australia. RP Schlosser, RJ (reprint author), Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,Ste 1130,POB 250550, Charleston, SC 29425 USA. EM schlossr@musc.edu NR 28 TC 0 Z9 0 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0886-4470 EI 1538-361X J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUL PY 2011 VL 137 IS 7 BP 702 EP 704 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 793GL UT WOS:000292808300010 PM 21768417 ER PT J AU Folmer, RL AF Folmer, Robert L. TI Repetitive Transcranial Magnetic Stimulation for Tinnitus SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Letter ID RTMS C1 [Folmer, Robert L.] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR 97239 USA. [Folmer, Robert L.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. RP Folmer, RL (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Robert.Folmer@va.gov NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUL PY 2011 VL 137 IS 7 BP 730 EP 730 PG 1 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 793GL UT WOS:000292808300021 PM 21768426 ER PT J AU Johnson, MR Singh, JA Stewart, T Gioe, TJ AF Johnson, Michael R. Singh, Jasvinder A. Stewart, Thomas Gioe, Terence J. TI Patient Understanding and Satisfaction in Informed Consent for Total Knee Arthroplasty: A Randomized Study SO ARTHRITIS CARE & RESEARCH LA English DT Article ID SURGERY; RECALL AB Objective. Informed consent is a critical component of all surgical procedures, but patients' understanding and recall of the potential risks/benefits is poor. We hypothesized that utilization of multiple standardized education modalities in the informed consent process would allow for better retention and a more informed patient. Methods. A total of 151 patients undergoing primary total knee arthroplasty (TKA) were randomized to 3 groups: group 1 received standardized informed consent and a paper handout detailing the risks/benefits of TKA; group 2 received standardized informed consent, a paper handout, and a video discussing the risks/benefits of TKA; and group 3 followed the same process as group 2 plus formal nurse education. All patients completed a 15-item questionnaire (risks, indications, and expectations) immediately following this consent process on the morning of surgery and 6 weeks postoperatively. We used t-test and analysis of variance for data analyses. Results. There was no difference (P = 0.79) in satisfaction with the consent process between the 3 groups; 92-97% of the patients rated the consent process as good to excellent at all time points. The number of correct answers did not differ significantly between the groups at any time period (P = 0.31-0.81). Scores dropped significantly (P = 0.004) from preoperatively to the 6-week postoperative visit in all groups combined. A higher level of satisfaction with the process was reflected in higher scores preoperatively in all groups (P = 0.028). Conclusion. Preoperatively, patients satisfied with the consent process may have better recall of risks/benefits and expectations of surgery. Neither retention nor satisfaction was influenced by reinforcement methods, such as video or nurse education; they may therefore be unnecessary. C1 [Johnson, Michael R.; Stewart, Thomas; Gioe, Terence J.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama, Birmingham, AL USA. [Gioe, Terence J.] Minneapolis Vet Affairs Med Ctr, Minneapolis, MN 55417 USA. RP Gioe, TJ (reprint author), Minneapolis Vet Affairs Med Ctr, Sect 112E,1 Vet Dr, Minneapolis, MN 55417 USA. EM tjgioe@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Minneapolis VA Medical Center; Birmingham VA Medical Center; URL Pharmaceuticals; Savient; Takeda; Novartis; Abbott; Wyeth; Amgen; Arthritis Foundation; University of Minnesota; Cochrane Library; Department of Veterans Affairs; Allergan; Depuy, Inc. FX Supported by the Minneapolis VA Medical Center and the Birmingham VA Medical Center.; Dr. Singh has received consultant fees, speaking fees. and/or. honoraria (less than $10,000 each) from URL Pharmaceuticals, Savient, Takeda, Novartis, and Abbott; research and travel grants from Takeda, Savient, Wyeth, Amgen, the Arthritis Foundation, University of Minnesota, Cochrane Library, and Department of Veterans Affairs; and investigator-initiator grants from Allergan, Savient, and Takeda. Dr. Gioe has received research support (more than $10,000) from Depuy, Inc. NR 20 TC 11 Z9 11 U1 0 U2 1 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 JUL PY 2011 VL 63 IS 7 BP 1048 EP 1054 DI 10.1002/acr.20475 PG 7 WC Rheumatology SC Rheumatology GA 793GU UT WOS:000292809200017 PM 21485018 ER PT J AU Lombardi, R Nin, N Lorente, JA Frutos-Vivar, F Ferguson, ND Hurtado, J Apezteguia, C Desmery, P Raymondos, K Tomicic, V Cakar, N Gonzalez, M Elizalde, J Nightingale, P Abroug, F Jibaja, M Arabi, Y Moreno, R Matamis, D Anzueto, A Esteban, A AF Lombardi, Raul Nin, Nicolas Lorente, Jose A. Frutos-Vivar, Fernando Ferguson, Niall D. Hurtado, Javier Apezteguia, Carlos Desmery, Pablo Raymondos, Konstantinos Tomicic, Vinko Cakar, Nahit Gonzalez, Marco Elizalde, Jose Nightingale, Peter Abroug, Fekri Jibaja, Manuel Arabi, Yaseen Moreno, Rui Matamis, Dimitros Anzueto, Antonio Esteban, Andres CA VENTILA Grp TI An Assessment of the Acute Kidney Injury Network Creatinine-Based Criteria in Patients Submitted to Mechanical Ventilation SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; INTENSIVE-CARE-UNIT; CRITICALLY-ILL PATIENTS; SERUM CREATININE; CARDIOTHORACIC SURGERY; HOSPITALIZED-PATIENTS; RIFLE CRITERIA; MORTALITY; OUTCOMES; CLASSIFICATION AB Background and objectives The aim of our study was to assess the new diagnostic criteria of acute kidney injury (AKI) proposed by the Acute Kidney Injury Network (AKIN) in a large cohort of mechanically ventilated patients. Design, setting, participants, & measurements This is a prospective observational cohort study enrolling 2783 adult intensive care unit patients under mechanical ventilation (MV) with data on serum creatinine concentration (SCr) in the first 48 hours. The absolute and the relative AKIN diagnostic criteria (changes in SCr >= 0.3 mg/dl or >= 50% over the first 48 hours of MV, respectively) were analyzed separately. In addition, patients were classified into three groups according to their change in SCr (Delta SCr) over the first day on MV (Delta SCr): group 1, Delta SCr <= -0.3 mg/dl; group 2, Delta SCr between -0.3 and +0.29 mg/dl; and group 3, Delta SCr >= +0.3 mg/dl). The primary end point was in-hospital mortality, and secondary end points were intensive care unit and hospital length of stay, and duration of MV. Results Of 2783 patients, 803 (28.8%) had AKI according to both criteria: 431 only absolute (AKI(A)), 362 both relative and absolute (AKI(R+A)), and 10 only relative. The relative criterion identified more patients when baseline SCr (SCr(0)) was <0.9 mg/dl and the absolute when SCr(0) was >1.5 mg/dl. The diagnosis of AKI was associated with mortality. Conclusions Our study confirms the validity of the AKIN criteria in a population of mechanically patients and the criteria's relationship with the baseline SCr. Clin J Am Soc Nephrol 6: 1547-1555, 2011. doi: 10.2215/CJN.09531010 C1 [Esteban, Andres] Hosp Univ Getafe, Intens Care Unit, Madrid 28905, Spain. [Lombardi, Raul] Inst Med Previs & Asistencia IMPASA, Montevideo, Uruguay. [Nin, Nicolas; Lorente, Jose A.; Frutos-Vivar, Fernando; Esteban, Andres] Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain. [Ferguson, Niall D.] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada. [Ferguson, Niall D.] Univ Toronto, Dept Med, Div Respirol, Univ Hlth Network, Toronto, ON, Canada. [Hurtado, Javier] Hosp Espanol, Hosp Clin, Depto Fisiopatol, Montevideo, Uruguay. [Apezteguia, Carlos] Hosp Profesor A Posadas, Buenos Aires, DF, Argentina. [Desmery, Pablo] Sanatorio Mitre, Buenos Aires, DF, Argentina. [Raymondos, Konstantinos] Hannover Med Sch, D-30623 Hannover, Germany. [Tomicic, Vinko] Clin Alemana Santiago, Santiago, Chile. [Cakar, Nahit] Dokuz Eylun Univ, Istanbul, Turkey. [Gonzalez, Marco] Univ Pontificia Bolivariana, Medellin, Colombia. [Gonzalez, Marco] Clin Medellin, Medellin, Colombia. [Elizalde, Jose] Hosp ABC, Mexico City, DF, Mexico. [Nightingale, Peter] Wythenshawe Hosp, Manchester M23 9LT, Lancs, England. [Abroug, Fekri] Fattouma Bourguiba Monastir, Monastir, Tunisia. [Arabi, Yaseen] King Fahad Natl Guard Hosp, Riyadh, Saudi Arabia. [Moreno, Rui] Ctr Hosp Lisboa Cent, EPE, Hosp Santo Antonio Capuchos, Lisbon, Portugal. [Matamis, Dimitros] Papageorgiou Gen Hosp, Thessaloniki, Greece. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, Antonio] Audie L Murphy Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Esteban, A (reprint author), Hosp Univ Getafe, Intens Care Unit, Carretera Toledo Km 12,500, Madrid 28905, Spain. EM aesteban@ucigetafe.com RI ; Pesenti, Antonio/H-7483-2012; koca, ugur/F-1265-2016; Malbrain, Manu/B-3680-2017 OI CHIUMELLO, DAVIDE ALBERTO/0000-0001-9260-3930; Darmon, Michael/0000-0003-4198-8038; koca, ugur/0000-0002-2949-4265; Malbrain, Manu/0000-0002-1816-5255; Severgnini, Paolo/0000-0001-8027-0059; Frutos-Vivar, Fernando/0000-0002-4648-9636; Ferguson, Niall/0000-0002-6213-5264 FU Instituto de Salud Carlos III, Spain FX This study was supported by CIBERES from Instituto de Salud Carlos III, Spain. The study sponsor had no role in study design, in the collection, analysis, and interpretation of data;, in the writing of the report, nor in the decision to submit the paper for publication. NR 26 TC 13 Z9 14 U1 0 U2 9 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 JUL PY 2011 VL 6 IS 7 BP 1547 EP 1555 DI 10.2215/CJN.09531010 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 790VL UT WOS:000292618300008 PM 21700822 ER PT J AU Dalrymple, LS Mohammed, SM Mu, Y Johansen, KL Chertow, GM Grimes, B Kaysen, GA Nguyen, DV AF Dalrymple, Lorien S. Mohammed, Sandra M. Mu, Yi Johansen, Kirsten L. Chertow, Glenn M. Grimes, Barbara Kaysen, George A. Nguyen, Danh V. TI Risk of Cardiovascular Events after Infection-Related Hospitalizations in Older Patients on Dialysis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; CASE SERIES; INFLAMMATION; SEPTICEMIA; STROKE; SYSTEM AB Background and objectives Infection and cardiovascular disease are leading causes of hospitalization and death in patients on dialysis. The objective of this study was to determine whether an infection-related hospitalization increased the short-term risk of a cardiovascular event in older patients on dialysis. Design, setting, participants, & measurements With use of the United States Renal Data System, patients aged 65 to 100 years who started dialysis between January 1, 2000, and December 31, 2002, were examined. All hospitalizations were examined from study entry until time of transplant, death, or December 31, 2004. All discharge diagnoses were examined to determine if an infection occurred during hospitalization. Only principal discharge diagnoses were examined to ascertain cardiovascular events of interest. We used the self-controlled case-series method to estimate the relative incidence of a cardiovascular event within 90 days after an infection-related hospitalization as compared with other times not within 90 days of such a hospitalization. Results A total of 16,874 patients had at least one cardiovascular event and were included in the self-controlled case-series analysis. The risk of a cardiovascular event was increased by 25% in the first 30 days after an infection and was overall increased 18% in the 90 days after an infection-related hospitalization relative to control periods. Conclusions The first 90 days, and in particular the first 30 days, after an infection-related hospitalization is a high-risk period for cardiovascular events and may be an important timeframe for cardiovascular risk reduction, monitoring, and intervention in older patients on dialysis. Clin J Am Soc Nephrol 6: 1708-1713, 2011. doi: 10.2215/CJN.10151110 C1 [Dalrymple, Lorien S.] Univ Calif Davis, Div Nephrol, Dept Med, Sacramento, CA 95817 USA. [Mohammed, Sandra M.; Mu, Yi; Nguyen, Danh V.] Univ Calif Davis, Dept Publ Hlth Sci, Sacramento, CA 95817 USA. [Kaysen, George A.] Univ Calif Davis, Dept Biochem & Mol Med, Sacramento, CA 95817 USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Johansen, Kirsten L.; Grimes, Barbara] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Johansen, Kirsten L.; Chertow, Glenn M.; Grimes, Barbara] US Renal Data Syst Nutr Special Studies Ctr, San Francisco, CA USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA. [Kaysen, George A.] Dept Vet Affairs Mather, Sacramento, CA USA. RP Dalrymple, LS (reprint author), Univ Calif Davis, Div Nephrol, Dept Med, 4150 5 St,Suite 3500, Sacramento, CA 95817 USA. EM Lorien.Dalrymple@ucdmc.ucdavis.edu FU National Center for Research Resources (NCRR) [UL1 RR024146]; National Institutes of Diabetes and Digestive and Kidney Diseases [N01-DK-7-0005] FX This publication was made possible by Grant UL1 RR024146 from the National Center for Research Resources (NCRR) and Contract N01-DK-7-0005 from the National Institutes of Diabetes and Digestive and Kidney Diseases. NR 13 TC 17 Z9 17 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 JUL PY 2011 VL 6 IS 7 BP 1708 EP 1713 DI 10.2215/CJN.10151110 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 790VL UT WOS:000292618300027 PM 21566109 ER PT J AU Bauman, WA Cirnigliaro, CM La Fountaine, MF Jensen, AM Wecht, JM Kirshblum, SC Spungen, AM AF Bauman, W. A. Cirnigliaro, C. M. La Fountaine, M. F. Jensen, A. M. Wecht, J. M. Kirshblum, S. C. Spungen, A. M. TI A Small-Scale Clinical Trial to Determine the Safety and Efficacy of Testosterone Replacement Therapy in Hypogonadal Men with Spinal Cord Injury SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE lean tissue mass; tetraplegia; paraplegia; hypogonadism; androgen replacement therapy ID RANDOMIZED CONTROLLED-TRIAL; RESTING ENERGY-EXPENDITURE; BODY-COMPOSITION; MUSCLE STRENGTH; ELDERLY-MEN; OLDER MEN; INDIVIDUALS; TETRAPLEGIA; PARAPLEGIA; ADULTS AB Men with spinal cord injury are at an increased risk for secondary medical conditions, including metabolic disorders, accelerated musculoskeletal atrophy, and, for some, hypogonadism, a deficiency, which may further adversely affect metabolism and body composition. A prospective, open label, controlled drug intervention trial was performed to determine whether 12 months of testosterone replacement therapy increases lean tissue mass and resting energy expenditure in hypogonadal males with spinal cord injury. Healthy eugonadal (n = 11) and hypogonadal (n = 11) outpatients with chronic spinal cord injury were enrolled. Hypogonadal subjects received transdermal testosterone (5 or 10 mg) daily for 12 months. Measurements of body composition and resting energy expenditure were obtained at baseline and 12 months. The testosterone replacement therapy group increased lean tissue mass for total body (49.6 +/- 7.6 vs. 53.1 +/- 6.9 kg; p <0.0005), trunk (24.1 +/- 4.1 vs. 25.8 +/- 3.8 kg; p <0.005), leg (14.5 +/- 2.7 vs. 15.8 +/- 2.6 kg; p = 0.005), and arm (7.6 +/- 2.3 vs. 8.0 +/- 2.2 kg; p <0.005) from baseline to month 12. After testosterone replacement therapy, resting energy expenditure (1328 +/- 262 vs. 1440 +/- 262 kcal/d; p <0.01) and percent predicted basal energy expenditure (73 +/- 9 vs. 79 +/- 10%; p <0.05) were significantly increased. In conclusion, testosterone replacement therapy significantly improved lean tissue mass and energy expenditure in hypogonadal men with spinal cord injury, findings that would be expected to influence the practice of clinical care, if confirmed. Larger, randomized, controlled clinical trials should be performed to confirm and extend our preliminary findings. C1 [Bauman, W. A.; Cirnigliaro, C. M.; La Fountaine, M. F.; Jensen, A. M.; Wecht, J. M.; Spungen, A. M.] James J Peters VA Med Ctr, VA RR&D Natl Ctr Excellence Med Consequences Spin, Bronx, NY 10468 USA. [Bauman, W. A.; La Fountaine, M. F.; Wecht, J. M.; Spungen, A. M.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Bauman, W. A.; La Fountaine, M. F.; Spungen, A. M.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauman, W. A.; Wecht, J. M.; Spungen, A. M.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Kirshblum, S. C.] Kessler Inst Rehabil, W Orange, NJ USA. [Kirshblum, S. C.] Univ Med & Dent New Jersey, Dept Phys Med & Rehabil, Newark, NJ 07103 USA. RP Bauman, WA (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM william.bauman@va.gov FU James J Peters VA Medical Center, Bronx, NY; Department of Veterans Affairs Rehabilitation Research & Development Service; Kessler Institute for Rehabilitation, West Orange, NJ; Rehabilitation Research & Development (RR & D) National Center of Excellence for the Medical Consequences of Spinal Cord Injury [B2648C, B4162C] FX The authors wish to thank the James J Peters VA Medical Center, Bronx, NY, the Department of Veterans Affairs Rehabilitation Research & Development Service, and the Kessler Institute for Rehabilitation, West Orange, NJ for their support. This work was funded by a Rehabilitation Research & Development (RR & D) National Center of Excellence for the Medical Consequences of Spinal Cord Injury (# B2648C & B4162C). This work has the Clinical Trial Registration Number: NCT00266864. NR 31 TC 17 Z9 18 U1 0 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JUL PY 2011 VL 43 IS 8 BP 574 EP 579 DI 10.1055/s-0031-1280797 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 794DQ UT WOS:000292876100010 PM 21717386 ER PT J AU Muntner, P Halanych, JH Reynolds, K Durant, R Vupputuri, S Sung, VW Meschia, JF Howard, VJ Safford, MM Krousel-Wood, M AF Muntner, Paul Halanych, Jewell H. Reynolds, Kristi Durant, Raegan Vupputuri, Suma Sung, Victor W. Meschia, James F. Howard, Virginia J. Safford, Monika M. Krousel-Wood, Marie TI Low Medication Adherence and the Incidence of Stroke Symptoms Among Individuals With Hypertension: The REGARDS Study SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID TRANSIENT ISCHEMIC ATTACK; BLOOD-PRESSURE CONTROL; RISK-FACTORS; PREDICTIVE-VALIDITY; GENERAL-POPULATION; RACIAL-DIFFERENCES; QUESTIONNAIRE; ASSOCIATION; PREVALENCE; METAANALYSIS AB The authors analyzed data on 9950 participants taking antihypertensive medications in the nationwide Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine the association between medication adherence and incident stroke symptoms. Medication adherence was assessed using a validated 4-item self-report scale and participants were categorized into 4 groups (scores of 0, 1, 2, and 3 or 4, with higher scores indicating worse adherence). The incidence of 6 stroke symptoms (sudden weakness on one side of the body, numbness, painless loss of vision in one or both eyes, loss of half vision, losing the ability to understand people, and losing the ability to express oneself verbally or in writing) was assessed via telephone interviews every 6 months. During a median of 4 years, the incidence of any stroke symptom was 14.6%, 17.9%, 20.2%, and 24.9% among participants with adherence scores of 0, 1, 2, and 3 or 4, respectively (P <.001). The multivariable adjusted hazard ratio (95% confidence interval) for any stroke symptom associated with adherence scores of 1, 2, and 3 or 4, vs 0, was 1.20 (1.04-1.39), 1.23 (0.94-1.60), and 1.59 (1.08-2.33), respectively (P <.001). Worse adherence was also associated with higher multivariable adjusted hazard ratios for each of the 6 stroke symptoms. J Clin Hypertens (Greenwich). 2011; 13: 479-486. (c) 2011 Wiley Periodicals, Inc. C1 [Muntner, Paul] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Muntner, Paul; Halanych, Jewell H.; Durant, Raegan; Safford, Monika M.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Reynolds, Kristi] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Durant, Raegan] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Vupputuri, Suma] Kaiser Permanente Georgia, Ctr Hlth Res, Atlanta, GA USA. [Sung, Victor W.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Krousel-Wood, Marie] Ochsner Clin Fdn, Ctr Hlth Res, New Orleans, LA USA. [Krousel-Wood, Marie] Tulane Univ, Dept Epidemiol, New Orleans, LA 70118 USA. [Krousel-Wood, Marie] Tulane Univ, Dept Family & Community Med, New Orleans, LA 70118 USA. RP Muntner, P (reprint author), Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, RPHB 230J 1530,3rd Ave S, Birmingham, AL 35294 USA. EM pmuntner@uab.edu RI Krousel-Wood, Marie Antoinette/D-4718-2011 OI Sung, Victor/0000-0003-1024-3404 FU National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services [U01 NS041588]; National Institute on Aging [R01 AG022536]; [R01 HL80477] FX This research project is supported by a cooperative agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health. Representatives of the funding agency have been involved in the review of the manuscript but not directly involved in the collection, management, analysis, or interpretation of the data. The authors thank the investigators, staff, and participants of the REGARDS study for their valuable contributions. A full list of participating REGARDS investigators and institutions can be found at http://www.regardsstudy.org. Drs Muntner and Krousel-Wood received support from the National Institute on Aging grant number R01 AG022536. Drs Safford, Halanych, and Durant received support from grant number R01 HL80477. NR 41 TC 18 Z9 18 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JUL PY 2011 VL 13 IS 7 BP 479 EP 486 DI 10.1111/j.1751-7176.2011.00464.x PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 793SQ UT WOS:000292843800004 PM 21762360 ER PT J AU Dighe, MK Bhargava, P Wright, J AF Dighe, Manjiri K. Bhargava, Puneet Wright, Jonathan TI Urinary Bladder Masses: Techniques, Imaging Spectrum, and Staging SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Review DE bladder carcinoma; imaging; cystoscopy; urinary bladder; transitional cell carcinoma ID TRANSITIONAL-CELL-CARCINOMA; RADIOLOGIC-PATHOLOGICAL CORRELATION; VIRTUAL CYSTOSCOPY; FLUORESCENCE CYSTOSCOPY; UROTHELIAL CARCINOMA; SECONDARY NEOPLASMS; MALIGNANT-LYMPHOMA; GROSS HEMATURIA; RENAL PELVIS; CT UROGRAPHY AB Bladder carcinoma is the fourth most common cancer in men and women. Knowledge of imaging options and appearance is necessary for both radiologists and urologists. Transitional cell carcinoma is the most common bladder neoplasm with squamous cell and adenocarcinoma found in less than 10% of cases. Benign lesions are uncommon, but some can be suggested by their imaging appearance. Similarly, malignant lesions often have suggestive appearance and/or location. Cystoscopy allows tissue diagnosis and treatment of superficial lesions. Although magnetic resonance imaging (MRI) and computed tomography (CT) both have limitations in detailing depth of muscle invasion, both have a prominent role helping to define the lesion and in staging. This article illustrates the role of MRI and CT in evaluating bladder masses with a discussion of the newer techniques of MR diffusion-weighted imaging and virtual cystoscopy by CT or MRI. This article reviews the multiple benign and malignant lesions of the bladder so that the reader can appreciate the role of cystoscopy, CT, MRI, diffusion-weighted imaging, and virtual cystoscopy in dealing with these relatively common tumors. C1 [Dighe, Manjiri K.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. [Bhargava, Puneet] VA Puget Sound HCS, Dept Radiol, Seattle, WA USA. [Wright, Jonathan] Univ Washington, Med Ctr, Dept Urol, Seattle, WA 98195 USA. RP Dighe, MK (reprint author), Univ Washington, Med Ctr, Dept Radiol, 1959 NE Pacific St,Box 357115, Seattle, WA 98195 USA. EM dighe@u.washington.edu RI Bhargava, Puneet /F-1330-2011 OI Bhargava, Puneet/0000-0002-3849-9666 NR 79 TC 8 Z9 9 U1 0 U2 4 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 JUL-AUG PY 2011 VL 35 IS 4 BP 411 EP 424 DI 10.1097/RCT.0b013e31821c2e9d PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 792TR UT WOS:000292773800001 PM 21765295 ER PT J AU Mehta, KM Pierluissi, E Boscardin, WJ Kirby, KA Walter, LC Chren, MM Palmer, RM Counsell, SR Landefeld, CS AF Mehta, Kala M. Pierluissi, Edgar Boscardin, W. John Kirby, Katharine A. Walter, Louise C. Chren, Mary-Margaret Palmer, Robert M. Counsell, Steven R. Landefeld, C. Seth TI A Clinical Index to Stratify Hospitalized Older Adults According to Risk for New-Onset Disability SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hospitalization; prognosis; disability; activities of daily living ID ACUTE MEDICAL ILLNESS; RANDOMIZED CONTROLLED-TRIAL; FUNCTIONAL DECLINE; ELDERLY-PATIENTS; OUTCOMES; PREDICTORS; HEALTH; CARE; INTERVENTION; TRANSITIONS AB BACKGROUND: Many older adults who are independent prior to hospitalization develop a new disability by hospital discharge. Early risk stratification for new-onset disability may improve care. Thus, this study's objective was to develop and validate a clinical index to determine, at admission, risk for new-onset disability among older, hospitalized adults at discharge. DESIGN: Data analyses derived from two prospective studies. SETTING: Two teaching hospitals in Ohio. PARTICIPANTS: Eight hundred eighty-five patients aged 70 years and older were discharged from a general medical service at a tertiary care hospital (mean age 78, 59% female) and 753 patients discharged from a separate community teaching hospital (mean age 79, 63% female). All participants reported being independent in five activities of daily living (ADLs: bathing, dressing, transferring, toileting, and eating) 2 weeks before admission. MEASUREMENTS: New-onset disability, defined as a new need for personal assistance in one or more ADLs at discharge in participants who were independent 2 weeks before hospital admission. RESULTS: Seven independent risk factors known on admission were identified and weighted using logistic regression: age (80-89, 1 point; >= 90, 2 points); dependence in three or more instrumental ADLs at baseline (2 points); impaired mobility at baseline (unable to run, 1 point; unable to climb stairs, 2 points); dependence in ADLs at admission (2-3 ADLs, 1 point; 4-5 ADLs, 3 points); acute stroke or metastatic cancer (2 points); severe cognitive impairment (1 point); and albumin less than 3.0 g/dL (2 points). New-onset disability occurred in 6%, 13%, 18%, 34%, 35%, 45%, 50%, and 87% of participants with 0, 1, 2, 3, 4, 5, 6, and 7 or more points, respectively, in the derivation cohort (area under the receiver operating characteristic curve (AUC) = 0.784), and in 8%, 10%, 27%, 38%, 44%, 45%, 58%, and 83%, respectively, in the validation cohort (AUC = 0.784). The risk score also predicted (P<.001) disability severity, nursing home placement, and long-term survival. CONCLUSION: This clinical index determines risk for new-onset disability in hospitalized older adults and may inform clinical care. J AmGeriatr Soc 59:1206-1216, 2011. C1 [Mehta, Kala M.; Pierluissi, Edgar; Boscardin, W. John; Kirby, Katharine A.; Walter, Louise C.; Landefeld, C. Seth] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. [Boscardin, W. John; Landefeld, C. Seth] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94121 USA. [Mehta, Kala M.; Boscardin, W. John; Walter, Louise C.; Chren, Mary-Margaret; Landefeld, C. Seth] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program, San Francisco, CA USA. [Palmer, Robert M.] Univ Pittsburgh, Div Geriatr Med & Gerontol, Pittsburgh, PA USA. [Counsell, Steven R.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. [Counsell, Steven R.] Indiana Univ, Sch Med, Indiana Univ Ctr Aging Res, Indianapolis, IN USA. RP Mehta, KM (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM Kala.mehta@ucsf.edu FU National Institute on Aging (NIA) [RO1 AG029233, K-01AG025444, AG-10418-03]; S.D. Bechtel, Jr. Foundation; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health [K24 AR052667]; National Cancer Institute [R01CA134425-01A2]; Veterans Affairs Merit Review [IIR 04-427]; John A. Hartford Foundation [88277-3G, 2006-0108]; Summa Health System Foundation FX This work was supported by National Institute on Aging (NIA) Grant RO1 AG029233 and a grant from the S.D. Bechtel, Jr. Foundation (PI: Dr. Landefeld). Dr. Mehta was supported by a Research Career Scientist Award from the NIA (K-01AG025444). She was an affiliate of the Center for Aging in Diverse Communities at the University of California at San Francisco, a part of the P30 AG 15272 350 Resource Centers for Minority Aging Research Program (NIA, National Institute of Nursing Research, and the National Center for Minority Health and Health Disparities). Dr. Pierluissi was supported by an administrative supplement to NIA Grant RO1 AG029233. Dr. Chren was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (K24 AR052667). Dr. Walter was supported by a grant from the National Cancer Institute (R01CA134425-01A2) and a Veterans Affairs Merit Review Grant (IIR 04-427). The Acute Care for Elders studies were supported by grants from the John A. Hartford Foundation (88277-3G and 2006-0108), the NIA (AG-10418-03), and the Summa Health System Foundation. NR 49 TC 26 Z9 26 U1 6 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2011 VL 59 IS 7 BP 1206 EP 1216 DI 10.1111/j.1532-5415.2011.03409.x PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 791VT UT WOS:000292696100006 PM 21649616 ER PT J AU Brown, MA AF Brown, Mark A. TI Science Versus Policy in Establishing Equitable Agent Orange Disability Compensation Policy SO MILITARY MEDICINE LA English DT Article ID VIETNAM; HERBICIDES; VETERANS AB This article makes the case that current Agent Orange compensation policy for Vietnam War veterans is based neither wholly upon scientific findings about Agent Orange health effects nor on pure public health policy considerations. Rather, it is the logical culmination of decades of experience among policy makers and public health scientists trying to establish clear-cut, equitable, and scientifically defensible compensation policy in the face of limited relevant science and poor or nonexistent exposure data-all within the broader context of Veterans Affairs disability compensation policies, and a deep-seated commitment to support the men and women who served their country during the Vietnam War. Finally, attempts to update current policy will benefit from an understanding of this background. C1 [Brown, Mark A.] US Dept Vet Affairs, Off Publ Hlth & Environm Agents Serv, Richmond, VA USA. RP Brown, MA (reprint author), 803 Aspen St NW, Washington, DC 20012 USA. NR 21 TC 3 Z9 3 U1 0 U2 3 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 JUL PY 2011 VL 176 IS 7 SU S BP 35 EP 40 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 792XQ UT WOS:000292784100011 PM 21916328 ER PT J AU Yacoub, R Ferrucci, S AF Yacoub, Robert Ferrucci, Steven TI Charles Bonnet syndrome SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION LA English DT Article DE Charles Bonnet syndrome; Visual hallucinations; Visual impairment ID COMPLEX VISUAL HALLUCINATIONS; MACULAR DEGENERATION; VISION; IMPAIRMENT AB BACKGROUND: Charles Bonnet syndrome (CBS) involves nonthreatening hallucinations in patients who have no neurological and no psychological abnormalities but with significant visual impairment secondary to ocular disease, such as macular degeneration and diabetic retinopathy. Because of the fear of a mental illness being diagnosed, patients are often reluctant to discuss these hallucinations. CASE REPORTS: Three cases are presented of patients who experienced CBS caused by decreased vision. Each patient had decreased vision and related visual hallucinations that were consistent with CBS. The first patient underwent magnetic resonance imaging and psychological evaluation, which confirmed our suspicion. The other 2 patents were not willing to undergo further testing, so our diagnosis is presumptive. CONCLUSION: Management for these hallucinations includes treatment of the actual ocular disease as well as optimizing vision for the patient using appropriate low vision devices. As the population continues to age, more patients will be seen with reduced vision caused by a myriad of ocular diseases, increasing the likelihood that more patients may present with CBS in the future. It is therefore prudent to become familiar with the syndrome so primary care optometrists can properly identify CBS and help their patients deal with it. Optometry 2011;82:421-427 C1 [Yacoub, Robert; Ferrucci, Steven] So Calif Coll Optometry, Fullerton, CA USA. [Ferrucci, Steven] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr & Nursing Home, Sepulveda, CA USA. RP Ferrucci, S (reprint author), Sepulveda Vet Affairs Ambulatory Care Ctr, Dept Optometry, Sepulveda, CA 91343 USA. EM Steven.ferrucci@va.gov NR 32 TC 7 Z9 7 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-1839 J9 OPTOMETRY JI Optometry PD JUL PY 2011 VL 82 IS 7 BP 421 EP 427 DI 10.1016/j.optm.2010.11.014 PG 7 WC Ophthalmology SC Ophthalmology GA 791MU UT WOS:000292670100005 PM 21511535 ER PT J AU Hsia, RY Asch, SM Weiss, RE Zingmond, D Liang, LJ Han, WJ McCreath, H Sun, BC AF Hsia, Renee Y. Asch, Steven M. Weiss, Robert E. Zingmond, David Liang, Li-Jung Han, Weijuan McCreath, Heather Sun, Benjamin C. TI Hospital Determinants of Emergency Department Left Without Being Seen Rates SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID MEDICAL-CARE; LEAVE; ACCESS; PHYSICIAN; SERVICES; TRENDS; CONSEQUENCES; EXPERIENCE; CAPACITY; PATIENT AB Study objective: The proportion of patients who leave without being seen in the emergency department (ED) is an outcome-oriented measure of impaired access to emergency care and represents the failure of an emergency care delivery system to meet its goals of providing care to those most in need. Little is known about variation in the amount of left without being seen or about hospital-level determinants. Such knowledge is necessary to target hospital-level interventions to improve access to emergency care. We seek to determine whether hospital-level socioeconomic status case mix or hospital structural characteristics are predictive of ED left without being seen rates. Methods: We performed a cross-sectional study of all acute-care, nonfederal hospitals in California that operated an ED in 2007, using data from the California Office of Statewide Health Planning and Development database and the US census. Our outcome of interest was whether a visit to a given hospital ED resulted in left without being seen. The proportion of left without being seen was measured by the number of left without being seen cases out of the total number of visits. Results: We studied 9.2 million ED visits to 262 hospitals in California. The percentage of left without being seen varied greatly over hospitals, ranging from 0% to 20.3%, with a median percentage of 2.6%. In multivariable analyses adjusting for hospital-level socioeconomic status case mix, visitors to EDs with a higher proportion of low-income and poorly insured patients experienced a higher risk of left without being seen. We found that the odds of an ED visit resulting in left without being seen increased by a factor of 1.15 for each 10-percentage-point increase in poorly insured patients, and odds of left without being seen decreased by a factor of 0.86 for each $10,000 increase in household income. When hospital structural characteristics were added to the model, county ownership, trauma center designation, and teaching program affiliation were positively associated with increased probability of left without being seen (odds ratio 2.09; 1.62, and 2.14, respectively), and these factors attenuated the association with insurance status. Conclusion: Visitors to different EDs experience a large variation in their probability of left without being seen, and visitors to hospitals serving a high proportion of low-income and poorly insured patients are at disproportionately higher risk of leaving without being seen. Our findings suggest that there is room for substantial improvement in this outcome, and regional interventions can be targeted toward certain at-risk hospitals to improve access to emergency care. [Ann Emerg Med. 2011;58:24-32.] C1 [Hsia, Renee Y.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94110 USA. [Asch, Steven M.; Zingmond, David; Liang, Li-Jung; Sun, Benjamin C.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Weiss, Robert E.; Han, Weijuan; McCreath, Heather] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Asch, Steven M.; Sun, Benjamin C.] VA Greater Angeles Hlth Syst, Los Angeles, CA USA. RP Hsia, RY (reprint author), Univ Calif San Francisco, Dept Emergency Med, San Francisco Gen Hosp, 1001 Potrero Ave,1E21, San Francisco, CA 94110 USA. EM rhsia@sfghed.ucsf.edu FU Emergency Medicine Foundation; Agency for Healthcare Research and Quality [R03 HS18098]; UCLA Older Americans Independence Center NIH/NIA [P30-AG028748]; NIH/NCRR/OD [KL2 RR024130]; Robert Wood Johnson Foundation FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). This publication was supported by the Emergency Medicine Foundation (Dr. Sun), Agency for Healthcare Research and Quality (R03 HS18098) (Dr. Sun), UCLA Older Americans Independence Center NIH/NIA grant P30-AG028748 (Ms. Han and Drs. McCreath and Sun), NIH/NCRR/OD UCSF-CTSI grant number KL2 RR024130 (Dr. Hsia), and the Robert Wood Johnson Foundation Physician Faculty Scholars (Dr. Hsia). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of any of the funding agencies. NR 56 TC 26 Z9 26 U1 1 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JUL PY 2011 VL 58 IS 1 BP 24 EP 32 DI 10.1016/j.annemergmed.2011.01.009 PG 9 WC Emergency Medicine SC Emergency Medicine GA 786XL UT WOS:000292341100008 PM 21334761 ER PT J AU Yu, WD Feng, S Dakhova, O Creighton, CJ Cai, Y Wang, JH Li, RL Frolov, A Ayala, G Ittmann, M AF Yu, Wendong Feng, Shu Dakhova, Olga Creighton, Chad J. Cai, Yi Wang, Jianghua Li, Rile Frolov, Anna Ayala, Gustavo Ittmann, Michael TI FGFR-4 Arg(388) Enhances Prostate Cancer Progression via Extracellular Signal-Related Kinase and Serum Response Factor Signaling SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR-4; SQUAMOUS-CELL CARCINOMA; ANDROGEN RECEPTOR; BREAST-CANCER; ARG388 ALLELE; INTRAEPITHELIAL NEOPLASIA; RADICAL PROSTATECTOMY; REACTIVE STROMA; UP-REGULATION; EXPRESSION AB Purpose: Increased expression of FGFR-4 and its ligands have been linked to lethal prostate cancer (PCa). Furthermore, a germ line polymorphism in the FGFR-4 gene, resulting in arginine at codon 388 (Arg(388)) instead of glycine (Gly(388)), is associated with aggressive disease. The FGFR-4 Arg(388) variant results in increased receptor stability, sustained receptor activation, and increased motility and invasion compared with Gly(388). However, the impact of sustained signaling on cellular signal transduction pathways is unknown. Experimental Design: Expression microarray analysis of immortalized prostatic epithelial cells lines expressing FGFR-4 Arg(388) or Gly(388) was used to establish a gene signature associated with FGFR-4 Arg(388) expression. Transient transfection of reporters and inhibitors was used to establish the pathways activated by FGFR-4 Arg(388) expression. The impact of pathway knockdown in vitro and in an orthotopic model was assessed using inhibitors and/or short hairpin RNA (shRNA). Results: Expression of the FGFR-4 Arg(388) protein leads to increased activity of the extracellular signal-related kinase (ERK) pathway, increased activity of serum response factor (SRF) and AP1, and transcription of multiple genes that are correlated with aggressive clinical behavior in PCa. Increased expression of SRF is associated with biochemical recurrence in men undergoing radical prostatectomy. Consistent with these observations, knockdown of FGFR-4 Arg(388) in PCa cells decreases proliferation and invasion in vitro and primary tumor growth and metastasis in vivo. Conclusions: These studies define a signal transduction pathway downstream of FGFR-4 Arg(388) that acts via ERK and SRF to promote PCa progression. Clin Cancer Res; 17(13); 4355-66. (C) 2011 AACR. C1 [Yu, Wendong; Feng, Shu; Dakhova, Olga; Cai, Yi; Wang, Jianghua; Li, Rile; Frolov, Anna; Ayala, Gustavo; Ittmann, Michael] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Creighton, Chad J.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Yu, Wendong; Feng, Shu; Dakhova, Olga; Cai, Yi; Wang, Jianghua; Ittmann, Michael] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. RP Ittmann, M (reprint author), Baylor Coll Med, Dept Pathol, 1 Baylor Plaza, Houston, TX 77030 USA. EM mittmann@bcm.tmc.edu FU Department of Veterans Affairs; DOD [W81XWH-09-1-0172]; National Cancer Institute [1U54CA126568]; Baylor Prostate Cancer SPORE [P50CA058204]; Dan L. Duncan Cancer Center [P30CA125123] FX This work was supported by grants from the Department of Veterans Affairs Merit Review (M. Ittmann), the DOD Prostate Cancer Research program (W81XWH-09-1-0172; W. Yu), the National Cancer Institute to the Tumor Microenvironment Network (1U54CA126568), the Baylor Prostate Cancer SPORE (P50CA058204), and the Dan L. Duncan Cancer Center (P30CA125123) and by the use of the facilities of the Michael E. DeBakey VAMC. NR 50 TC 24 Z9 25 U1 0 U2 4 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 JUL 1 PY 2011 VL 17 IS 13 BP 4355 EP 4366 DI 10.1158/1078-0432.CCR-10-2858 PG 12 WC Oncology SC Oncology GA 788LO UT WOS:000292446600018 PM 21622724 ER PT J AU Grande, D Gollust, SE Asch, DA AF Grande, David Gollust, Sarah E. Asch, David A. TI Polling Analysis: Public Support For Health Reform Was Broader Than Reported And Depended On How Proposals Were Framed SO HEALTH AFFAIRS LA English DT Article ID OPINION; CARE AB The excessive focus of news organizations on "horse race" public opinion polls during the debate about health reform in 2010 left the impression that the public was fickle, as well as sharply divided on whether the government's role in health care should expand. We examined polling data and found that public support for health reform depended very much on how individual policies were described. For example, support for the public insurance option, which was not included in the final version of the Affordable Care Act, ranged from 46.5 percent to 64.6 percent depending on how pollsters worded their questions. Our findings indicate that public support for health reform was broader and more consistent than portrayed at the time. Going forward, policy makers should strive to communicate how health care policy choices are consistent with existing public preferences or should make changes to policy that reflect those preferences. C1 [Grande, David; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Grande, David] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Gollust, Sarah E.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Grande, D (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. EM dgrande@wharton.upenn.edu OI Asch, David/0000-0002-7970-286X FU Robert Wood Johnson Foundation; HealthWell Foundation FX Funding for this research was provided by the Robert Wood Johnson Foundation Health and Society Scholars Program. The funder had no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript. David Grande reports receiving research support from the HealthWell Foundation, serving as a consultant to the National Nursing Centers Consortium, providing expert testimony of behalf of the State of Vermont, receiving honoraria for lectures from Temple University and the Johns Hopkins University continuing medical education program, and previously serving as a voluntary member of the board of directors of the National Physicians Alliance. The authors thank Jeffrey Then for his research assistance. NR 16 TC 5 Z9 5 U1 1 U2 6 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUL PY 2011 VL 30 IS 7 BP 1242 EP 1249 DI 10.1377/hlthaff.2011.0180 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 789ET UT WOS:000292497600004 PM 21734196 ER PT J AU Loftis, JM AF Loftis, J. M. TI Sertoli cell therapy: A novel possible treatment strategy for treatment-resistant major depressive disorder SO MEDICAL HYPOTHESES LA English DT Article ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE PRODUCTION; PITUITARY-ADRENAL AXIS; LONG-TERM POTENTIATION; INDUCED RAT MODEL; HIPPOCAMPAL VOLUME; ANTIDEPRESSANT TREATMENT; WHITE-MATTER; PSYCHIATRIC-DISORDERS; MOOD DISORDERS AB By the year 2020, depression will be the 2nd most common health problem in the world. Current medications to treat depression are effective in less than 50% of patients. There is the need for novel treatments for depression to address the high rates of resistance to current treatment and the chronic residual symptoms in many patients treated for depression. The heterogeneity of major depressive disorder suggests that multiple neurocircuits and neurochemicals are involved in its pathogenesis thus, finding an alternative to neurotransmitter agonist- or antagonist-based treatments offers an important new approach. Cellular therapy is an emerging treatment strategy for multiple diseases, including depression. Based upon their in vivo function as "nurse cells" within the testis and the documented viability, efficacy, and safety of Sertoli cells transplanted into multiple tissues, including brain, the potential for these cells to provide a neuroprotective, anti-inflammatory, and trophic environment for neurons should be considered. It is proposed that the combination of self-protective, immunoregulatory and trophic properties of Sertoli cells may confer a unique potential for depression treatment and avoid many of the risks and challenges associated with stem cell therapies. At the very least, studies of the effects of Sertoli cell transplantation will add substantially to our understanding of the cellular and molecular processes that underlie depression. Published by Elsevier Ltd. C1 [Loftis, J. M.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA. [Loftis, J. M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. RP Loftis, JM (reprint author), 3710 SW US Vet Hosp Rd,Mail Code R&D 16, Portland, OR 97239 USA. EM jennifer.loftis2@va.gov FU Department of Veterans Affairs, Veterans Health Administration. Office of Research and Development, Clinical Sciences Research and Development; Oregon Health and Science University; VA Career Development Award FX This material is based upon work in part supported by the Department of Veterans Affairs, Veterans Health Administration. Office of Research and Development, Clinical Sciences Research and Development, as well as by the Oregon Health and Science University. This manuscript was funded through a VA Career Development Award (J.M.L). NR 151 TC 3 Z9 4 U1 3 U2 8 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD JUL PY 2011 VL 77 IS 1 BP 35 EP 42 DI 10.1016/j.mehy.2011.03.017 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 788FM UT WOS:000292430800010 PM 21454019 ER PT J AU Ikonomovic, MD Klunk, WE Abrahamson, EE Wuu, J Mathis, CA Scheff, SW Mufson, EJ DeKosky, ST AF Ikonomovic, M. D. Klunk, W. E. Abrahamson, E. E. Wuu, J. Mathis, C. A. Scheff, S. W. Mufson, E. J. DeKosky, S. T. TI Precuneus amyloid burden is associated with reduced cholinergic activity in Alzheimer disease SO NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; PITTSBURGH COMPOUND-B; A-BETA; FRONTAL-CORTEX; OLDER PERSONS; DEPOSITION; BRAIN; MEMORY; INDIVIDUALS; DIAGNOSIS AB Objective: This study examined the relationship between postmortem precuneus cholinergic enzyme activity, Pittsburgh compound B (PiB) binding, and soluble amyloid-beta concentration in mild cognitive impairment (MCI) and Alzheimer disease (AD). Methods: Choline acetyltransferase (ChAT) activity, [(3)H]PiB binding, and soluble amyloid-beta(1-42) (A beta 42) concentration were quantified in precuneus tissue samples harvested postmortem from subjects with no cognitive impairment (NCI), MCI, and mild AD and correlated with their last antemortem Mini-Mental State Examination (MMSE) score and postmortem pathologic evaluation according to the National Institute on Aging-Reagan criteria, recommendations of the Consortium to Establish a Registry for Alzheimer's Disease, and Braak stage. Results: Precuneus ChAT activity was lower in AD than in NCI and was comparable between MCI and NCI. Precuneus [(3)H]PiB binding and soluble A beta 42 levels were elevated in MCI and significantly higher in AD than in NCI. Across all case subjects, reduced ChAT activity was associated with increased [(3)H]PiB binding, increased soluble A beta 42, lower MMSE score, presence of the APOE*4 allele, and more advanced AD pathology. Conclusions: Despite accumulating amyloid burden, cholinergic enzyme activity is stable in the precuneus during prodromal AD. A decline in precuneus ChAT activity occurs only in clinical AD, when PiB binding and soluble A beta 42 levels are substantially elevated compared with those in MCI. Anti-amyloid interventions in MCI case subjects with a positive PiB PET scan may aid in reducing cholinergic deficits and cognitive decline later in the disease process. Neurology (R) 2011;77:39-47 C1 [Ikonomovic, M. D.; Klunk, W. E.; Abrahamson, E. E.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Ikonomovic, M. D.; Klunk, W. E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Mathis, C. A.] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15213 USA. [Ikonomovic, M. D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Wuu, J.] Univ Miami, Dept Neurol, Miami, FL USA. [Scheff, S. W.] Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40506 USA. [Mufson, E. J.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [DeKosky, S. T.] Univ Virginia, Sch Med, Off Dean, Charlottesville, VA 22908 USA. [DeKosky, S. T.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. RP Ikonomovic, MD (reprint author), Univ Pittsburgh, Dept Neurol, 200 Lothrop St,BST S521, Pittsburgh, PA 15213 USA. EM ikonomovicmd@upmc.edu OI Klunk, William/0000-0001-5512-0251 FU NIH [AG14449, AG025204, AG10161, AG05133, AG12138]; GE Healthcare; Forest Research Institute, Inc.; Elan/Janssen AI; Roche; AstraZeneca; Neuroptix Corporation; Anonymous Foundation; Cure Alzheimer's Fund; NIH/NIA; FDA; CDC; ALS Association; Muscular Dystrophy Association; Consolidated Anti-Aging Foundation; Bayer Schering Pharma; Biogen Idec; IBA; Takeda Pharmaceutical Company Limited; US Department of Energy; Dana Foundation FX Supported by NIH grants AG14449, AG025204, AG10161, AG05133, and AG12138.; Dr. Ikonomovic has served as a consultant for and received funding for travel from GE Healthcare; serves as an Associate Editor for Cardiovascular Psychiatry and Neurology; and receives research support from GE Healthcare, Forest Research Institute, Inc., and the NIH. Dr. Klunk serves on scientific advisory boards and as a consultant for GE Healthcare, Neuroptix Corporation, Elan/Janssen AI, Roche, Wyeth/Pfizer, and AstraZeneca; has received funding for travel from Elan/Janssen AI, Roche, and AstraZeneca; is author on patents re: PiB PET imaging and chrysamine-G derivatives for imaging and therapy; receives research support from GE Healthcare, Neuroptix Corporation, the NIH (NIA, NIBIB), Anonymous Foundation, and Cure Alzheimer's Fund; holds stock in Neuroptix Corporation; and receives license fee and royalty payment from GE Healthcare. Dr. Abrahamson reports no disclosures. J. Wuu has received research support from the NIH/NIA, the FDA, the CDC, the ALS Association, the Muscular Dystrophy Association, and the Consolidated Anti-Aging Foundation. Dr. Mathis serves on a scientific advisory board for Neuroptix Corporation; has received funding for travel and speaker honoraria from Elan/Janssen AI, GE Healthcare, Bayer Schering Pharma, Biogen Idec, IBA, and Takeda Pharmaceutical Company Limited; serves on the editorial board of Nuclear Medicine and Biology; serves/has served as a consultant for GE Healthcare, Elan/Janssen AI, Wyeth/Pfizer, and Novartis; is author on numerous US and international patents re: Amyloid imaging agents; receives/has received research support from GE Healthcare, Neuroptix Corporation, the NIH, the US Department of Energy, the Dana Foundation, and Anonymous Foundation; holds stock options in Neuroptix Corporation; and has received license fees and royalty payments from GE Healthcare and Neuroptix Corporation for patents re: Amyloid imaging agents. Dr. Scheff serves on a scientific advisory board for TIRR; serves on the editorial board of the Journal of Neurotrauma; and receives research support from the NIH. Dr. Mufson has served as a consultant for Ceregene and NeuroPhage and receives research support from the NIH. Dr. DeKosky has served on a scientific advisory board for Pfizer Inc and as a consultant for Eisai, PsychoGenics Inc., Merck, Elan/Wyeth, Novartis, Eli Lilly, and Janssen; is the site principal investigator at the University of Virginia Memory Disorders Clinics for experimental therapeutic trials of Alzheimer's disease medications for Elan, Novartis, Forest, and Janssen Pharmaceuticals; serves on the editorial boards of Annals of Neurology, Archives of Neurology, Neurodegenerative Diseases, Journal of Alzheimer's Disease, and Alzheimer Disease and Associated Disorders: An International Journal, and as Editor of Up to Date; receives research support from the NIH; and serves as a board member for the National Center for Complementary and Alternative Medicine, the American Board of Psychiatry and Neurology, and the Alzheimer's Association. NR 39 TC 38 Z9 42 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 JUL PY 2011 VL 77 IS 1 BP 39 EP 47 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 789TB UT WOS:000292538100010 PM 21700583 ER PT J AU Green, MF Lee, J Wynn, JK Mathis, KI AF Green, Michael F. Lee, Junghee Wynn, Jonathan K. Mathis, Kristopher I. TI Visual Masking in Schizophrenia: Overview and Theoretical Implications SO SCHIZOPHRENIA BULLETIN LA English DT Article DE visual masking; visual processing; neural tuning; schizophrenia ID BACKWARD-MASKING; BIPOLAR DISORDER; OBJECT-SUBSTITUTION; UNAFFECTED SIBLINGS; SOCIAL-PERCEPTION; DEFICITS; PERFORMANCE; PATTERNS; CORTEX; GABA AB Visual masking provides several key advantages for exploring the earliest stages of visual processing in schizophrenia: it allows for control over timing at the millisecond level, there are several well-supported theories of the underlying neurobiology of visual masking, and it is amenable to examination by electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI). In this paper, we provide an overview of the visual masking impairment schizophrenia, including the relevant theoretical mechanisms for masking impairment. We will discuss its relationship to clinical symptoms, antipsychotic medications, diagnostic specificity, and presence in at-risk populations. As part of this overview, we will cover the neural correlates of visual masking based on recent findings from EEG and fMRI. Finally, we will suggest a possible mechanism that could explain the patterns of masking findings and other visual processing findings in schizophrenia. C1 [Green, Michael F.; Lee, Junghee; Wynn, Jonathan K.; Mathis, Kristopher I.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Green, Michael F.; Lee, Junghee; Wynn, Jonathan K.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. RP Green, MF (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM mgreen@ucla.edu RI Lee, Junghee/C-5226-2014; Wynn, Jonathan/H-3749-2014 OI Lee, Junghee/0000-0001-9567-8700; Wynn, Jonathan/0000-0002-1763-8540 FU National Institute of Mental Health [043292, 065707]; VA FX National Institute of Mental Health Grants (043292 and 065707 to M.F.G.); VA Career Development Award (to J.K.W.). NR 49 TC 33 Z9 34 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUL PY 2011 VL 37 IS 4 BP 700 EP 708 DI 10.1093/schbul/sbr051 PG 9 WC Psychiatry SC Psychiatry GA 789PI UT WOS:000292527400009 PM 21606322 ER PT J AU Valenstein, M Kavanagh, J Lee, T Reilly, P Dalack, GW Grabowski, J Smelson, D Ronis, DL Ganoczy, D Woltmann, E Metreger, T Wolschon, P Jensen, A Poddig, B Blow, FC AF Valenstein, Marcia Kavanagh, Janet Lee, Todd Reilly, Peter Dalack, Gregory W. Grabowski, John Smelson, David Ronis, David L. Ganoczy, Dara Woltmann, Emily Metreger, Tabitha Wolschon, Patricia Jensen, Agnes Poddig, Barbara Blow, Frederic C. TI Using A Pharmacy-Based Intervention To Improve Antipsychotic Adherence Among Patients With Serious Mental Illness SO SCHIZOPHRENIA BULLETIN LA English DT Article DE adherence; antipsychotic medications; health services ID PRESCRIPTION REFILL COMPLIANCE; HEALTH-CARE EXPENDITURES; GROUP RANDOMIZED TRIALS; VALUE-ADDED UTILITIES; MEDICATION ADHERENCE; CONSORT STATEMENT; BIPOLAR DISORDER; REVISED RECOMMENDATIONS; NEUROLEPTIC TREATMENT; SCHIZOPHRENIA AB Background: Similar to patients with other chronic disorders, patients with serious mental illness (SMI) are often poorly adherent with prescribed medications. Objective: We conducted a randomized controlled trial examining the effectiveness of a pharmacy-based intervention (Meds-Help) in increasing antipsychotic medication adherence among Department of Veterans Affairs (VA) patients with SMI. We also examined the impact of Meds-Help on psychiatric symptoms, quality of life, and satisfaction with care. Methods: We enrolled 118 patients from 4 VA facilities with schizophrenia, schizoaffective, or bipolar disorder who were on long-term antipsychotics but had antipsychotic medication possession ratios (MPRs) <0.8 in the prior year. Patients were randomized to usual care (UC; n = 60) or the pharmacy-based intervention (Meds-Help; n = 58). We reassessed adherence at 6 and 12 months, at which time patients completed Positive and Negative Symptom Scales (PANSS), Quality of Well-being Scales (QWB), and Client Satisfaction Questionnaires (CSQ-8). Results: Prior to enrollment, Meds-Help and UC patients had mean antipsychotic MPRs of 0.54 and 0.55, respectively. At 6 months, mean MPRs were 0.91 for Meds-Help and 0.64 for UC patients; at 12 months, they were 0.86 for Meds-Help and 0.62 for UC patients. In multivariate analyses adjusting for patient factors, Meds-Help patients had significantly higher MPRs at 6 and 12 months (P < .0001). There were no significant differences between groups in PANSS, QWB, or CSQ-8 scores, but power to detect small effects was limited. Conclusions: Congruent with prior studies of patients with other disorders, a practical pharmacy-based intervention increased antipsychotic adherence among patients with SMI. However, SMI patients may require additional care management components to improve outcomes. C1 [Valenstein, Marcia; Ronis, David L.; Woltmann, Emily; Jensen, Agnes; Blow, Frederic C.] Dept Vet Affairs, Serious Mental Illness Treatment Res & Evaluat Ct, Ann Arbor, MI 48104 USA. [Valenstein, Marcia; Kavanagh, Janet; Dalack, Gregory W.; Ganoczy, Dara; Woltmann, Emily; Metreger, Tabitha; Blow, Frederic C.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Lee, Todd; Poddig, Barbara] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Lee, Todd] Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies, Chicago, IL 60611 USA. [Lee, Todd] Northwestern Univ, Feinberg Sch Med, Div Gen Internal Med, Chicago, IL 60611 USA. [Reilly, Peter; Grabowski, John; Wolschon, Patricia] Dept Vet Affairs, John D Dingell Med Ctr, Detroit, MI USA. [Smelson, David] Edith Nourse Rogers Mem Vet Hosp, Bedford, MA USA. [Smelson, David] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Ronis, David L.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. RP Valenstein, M (reprint author), Dept Vet Affairs, Serious Mental Illness Treatment Res & Evaluat Ct, Ann Arbor, MI 48104 USA. EM marciav@umich.edu FU Department of Veterans Affairs Health Services Research and Development [IIR 01-174-01] FX Department of Veterans Affairs Health Services Research and Development (IIR 01-174-01). NR 33 TC 29 Z9 30 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUL PY 2011 VL 37 IS 4 BP 727 EP 736 DI 10.1093/schbul/sbp121 PG 10 WC Psychiatry SC Psychiatry GA 789PI UT WOS:000292527400012 PM 19933540 ER PT J AU Wiederhold, NP Najvar, LK Bocanegra, RA Kirkpatrick, WR Patterson, TF AF Wiederhold, Nathan P. Najvar, Laura K. Bocanegra, Rosie A. Kirkpatrick, William R. Patterson, Thomas F. TI Caspofungin Dose Escalation for Invasive Candidiasis Due to Resistant Candida albicans SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID REDUCED ECHINOCANDIN SUSCEPTIBILITY; DOUBLE-BLIND TRIAL; AMPHOTERICIN-B; IN-VITRO; ASPERGILLUS-FUMIGATUS; MICAFUNGIN FK463; ADULT PATIENTS; IMMUNE-SYSTEM; MURINE MODEL; GLABRATA AB Previous in vivo studies have reported caspofungin dose escalation to be effective against Candida glabrata with reduced susceptibility. We hypothesized that higher doses of caspofungin would be effective against invasive candidiasis caused by the more virulent species Candida albicans, including isolates resistant to this echinocandin. Immunocompetent mice were inoculated with one of three C. albicans isolates, including one susceptible and two resistant isolates with different FKS1 hot spot 1 point mutations. Mice received daily caspofungin treatment for 7 days and were then followed off therapy for 2 weeks to assess survival. Kidney tissue and blood were collected, and fungal burden and serum (1 -> 3)-beta-D-glucan were measured. Significant differences in virulence were observed among the three C. albicans isolates, which translated into differences in responses to caspofungin. The most virulent of the resistant isolates studied (isolate 43001; Fks1p F641S) did not respond to caspofungin doses of up to 10 mg/kg of body weight, as there were no differences in survival (survival range, 0 to 12% with treatment), tissue burden, or (1 -> 3)-beta-D-glucan concentration compared to those for untreated controls. Higher doses of caspofungin did improve survival against the second resistant isolate (53264; Fks1p S645P) that demonstrated reduced virulence (5 and 10 mg/kg; 80% survival). In contrast, caspofungin doses as low as 1 mg/kg improved survival (85 to 95%) and reduced tissue burden and (1 -> 3)-beta-D-glucan concentration against the susceptible isolate (ATCC 90028). These data suggest that caspofungin dose escalation for invasive candidiasis may not be consistently effective against resistant C. albicans isolates, and this may be associated with the virulence of the strain. C1 [Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie A.; Kirkpatrick, William R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie A.; Kirkpatrick, William R.; Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Wiederhold, NP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, PERC MSC 6220,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM wiederholdn@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU Merck Co., Inc.; Pfizer; Schering-Plough; Merck; Basilea; Astellas; Nektar Therapeutics FX This work was supported in part by a research grant from the Investigator-Initiated Studies Program of Merck & Co., Inc.; N.P.W. has received research support from Pfizer, Schering-Plough, Merck, Basilea, and Astellas. T. F. P. has received research support from Basilea, Astellas, Merck, Pfizer, Schering-Plough, and Nektar Therapeutics and has served as a consultant for Basilea, Merck, Pfizer, and Toyama. NR 39 TC 29 Z9 32 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2011 VL 55 IS 7 BP 3254 EP 3260 DI 10.1128/AAC.01750-10 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 778FK UT WOS:000291687900026 PM 21502632 ER PT J AU Palacio, F Lewis, JS Sadkowski, L Echevarria, K Jorgensen, JH AF Palacio, Federico Lewis, James S., II Sadkowski, Lee Echevarria, Kelly Jorgensen, James H. TI Breakthrough Bacteremia and Septic Shock Due to Streptococcus anginosus Resistant to Daptomycin in a Patient Receiving Daptomycin Therapy SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Letter ID MILLERI; INFECTIONS; INTERMEDIUS C1 [Palacio, Federico] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. [Lewis, James S., II] Univ Hlth Syst, Dept Pharm, San Antonio, TX USA. [Sadkowski, Lee; Echevarria, Kelly] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Jorgensen, James H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. RP Palacio, F (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. EM jorgensen@uthscsa.edu NR 14 TC 9 Z9 9 U1 0 U2 1 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 JUL PY 2011 VL 55 IS 7 BP 3639 EP 3640 DI 10.1128/AAC.00231-11 PG 2 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 778FK UT WOS:000291687900086 PM 21502623 ER PT J AU Ovretveit, JC Shekelle, PG Dy, SM McDonald, KM Hempel, S Pronovost, P Rubenstein, L Taylor, SL Foy, R Wachter, RM AF Ovretveit, John C. Shekelle, Paul G. Dy, Sydney M. McDonald, Kathryn M. Hempel, Susanne Pronovost, Peter Rubenstein, Lisa Taylor, Stephanie L. Foy, Robbie Wachter, Robert M. TI How does context affect interventions to improve patient safety? An assessment of evidence from studies of five patient safety practices and proposals for research SO BMJ QUALITY & SAFETY LA English DT Article ID INTENSIVE-CARE UNITS AB Background: Logic and experience suggest that it is easier in some situations than in others to change behaviour and organisation to improve patient safety. Knowing which 'context factors' help and hinder implementation of different changes would help implementers, as well as managers, policy makers, regulators and purchasers of healthcare. It could help to judge the likely success of possible improvements, given the conditions that they have, and to decide which of these conditions could be modified to make implementation more effective. Methods: The study presented in this paper examined research to discover any evidence reported about whether or how context factors influence the effectiveness of five patient safety interventions. Results: The review found that, for these five diverse interventions, there was little strong evidence of the influence of different context factors. However, the research was not designed to investigate context influence. Conclusions: The paper suggests that significant gaps in research exist and makes proposals for future research better to inform decision-making. C1 [Ovretveit, John C.] Karolinska Inst, MMC, Med Management Ctr, S-17177 Stockholm, Sweden. [Shekelle, Paul G.] Univ Calif Los Angeles, RAND Corp, Los Angeles, CA USA. [Shekelle, Paul G.] VA Greater Los Angeles, Los Angeles, CA USA. [Pronovost, Peter] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care, Baltimore, MD USA. [McDonald, Kathryn M.] Stanford Univ, Stanford, CA 94305 USA. [Hempel, Susanne; Taylor, Stephanie L.] RAND Corp, Santa Monica, CA USA. [Pronovost, Peter] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Pronovost, Peter] Johns Hopkins Univ, Sch Med, Dept Hlth Policy & Management, Baltimore, MD 21205 USA. [Pronovost, Peter] Johns Hopkins Univ, Sch Med, Ctr Innovat Qual Patient Care, Baltimore, MD 21205 USA. [Rubenstein, Lisa] VA HSRD Ctr Excellence Study Healthcare Provider, North Hills, CA USA. [Foy, Robbie] Univ Leeds, Leeds Inst Hlth Sci, Leeds, W Yorkshire, England. [Wachter, Robert M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Ovretveit, JC (reprint author), Karolinska Inst, MMC, Med Management Ctr, Berzelius Vag 3, S-17177 Stockholm, Sweden. EM jovret@aol.com FU US Agency for Healthcare Research and Quality [HHSA-290-2009-10001C] FX This study was financed by the US Agency for Healthcare Research and Quality Contract No HHSA-290-2009-10001C. NR 29 TC 32 Z9 32 U1 1 U2 9 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD JUL PY 2011 VL 20 IS 7 BP 604 EP 610 DI 10.1136/bmjqs.2010.047035 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 778SX UT WOS:000291727100009 PM 21493589 ER PT J AU Taylor, SL Dy, S Foy, R Hempel, S McDonald, KM Ovretveit, J Pronovost, PJ Rubenstein, LV Wachter, RM Shekelle, PG AF Taylor, Stephanie L. Dy, Sydney Foy, Robbie Hempel, Susanne McDonald, Kathryn M. Ovretveit, John Pronovost, Peter J. Rubenstein, Lisa V. Wachter, Robert M. Shekelle, Paul G. TI What context features might be important determinants of the effectiveness of patient safety practice interventions? SO BMJ QUALITY & SAFETY LA English DT Article ID HEALTH-CARE RESEARCH; QUALITY IMPROVEMENT; GUIDELINES; RECOMMENDATIONS; IMPLEMENTATION; AGENCY AB Background: Differences in contexts (eg, policies, healthcare organisation characteristics) may explain variations in the effects of patient safety practice (PSP) implementations. However, knowledge of which contextual features are important determinants of PSP effectiveness is limited and consensus is lacking on a taxonomy of which contexts matter. Methods: Iterative, formal discussions were held with a 22-member technical expert panel composed of experts or leaders in patient safety, healthcare systems, and methods. First, potentially important contextual features were identified, focusing on five PSPs. Then, two surveys were conducted to determine the context likely to influence PSP implementations. Results: The panel reached a consensus on a taxonomy of four broad domains of contextual features important for PSP implementations: safety culture, teamwork and leadership involvement; structural organisational characteristics (eg, size, organisational complexity or financial status); external factors (eg, financial or performance incentives or PSP regulations); and availability of implementation and management tools (eg, training organisational incentives). Panelists also tended to rate specific patient safety culture, teamwork and leadership contexts as high priority for assessing their effects on PSP implementations, but tended to rate specific organisational characteristic contexts as high priority only for use in PSP evaluations. Panelists appeared split on whether specific external factors and implementation/management tools were important for assessment or only description. Conclusion: This work can guide research commissioners and evaluators on the contextual features of PSP implementations that are important to report or evaluate. It represents a first step towards developing guidelines on contexts in PSP implementation evaluations. However, the science of context measurement needs maturing. C1 [Taylor, Stephanie L.; Hempel, Susanne; Rubenstein, Lisa V.; Shekelle, Paul G.] RAND Corp, Santa Monica, CA USA. [Taylor, Stephanie L.; Rubenstein, Lisa V.; Shekelle, Paul G.] Vet Adm, Los Angeles, CA USA. [Dy, Sydney; Pronovost, Peter J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Foy, Robbie] Univ Leeds, Leeds Inst Hlth Sci, Leeds, W Yorkshire, England. [McDonald, Kathryn M.] Stanford Univ, Stanford, CA 94305 USA. [Ovretveit, John] Karolinska Inst, Med Management Ctr, Stockholm, Sweden. [Wachter, Robert M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Taylor, SL (reprint author), VA Greater Los Angeles, 16111 Plummer St,Bldg 25 152, North Hills, CA 91343 USA. EM stephanie.taylor8@va.gov FU Agency for Healthcare Research and Quality; Agency for Healthcare Research and Quality, US Department of Health and Human Services [HHSA-290-2009-10001C] FX Funding Agency for Healthcare Research and Quality.; The technical expert panel included Alyce S. Adams, PhD, Peter Angood, MD, David W. Bates, MD, MSc, Len Bickman, PhD, Celia Brown, PhD, Pascale Carayon, PhD, Sir Liam Donaldson, MD, Naihua Duan, PhD, Donna O. Farley, PhD, MPH, Trisha Greenhalgh, MD, John Haughom, MD, Eileen T. Lake, PhD, RN, Richard Lilford, MB BCh, PhD, Kathleen N. Lohr, PhD, Gregg S. Meyer, MD, MSc, Marlene Miller, MD, MSc, Duncan Neuhauser, PhD, Gery Ryan, PhD, Sanjay Saint, MD, MPH, Kaveh Shojania, MD, Stephen M. Shortell, PhD, MPH, David P. Stevens, MD, and Kieran Walshe, PhD. The research reported here was supported under Contract No. HHSA-290-2009-10001C from the Agency for Healthcare Research and Quality, US Department of Health and Human Services. The authors of this paper are responsible for its content. Statements in this paper should not be construed as endorsement by the Agency for Healthcare Research and Quality or the US Department of Health and Human Services. NR 31 TC 60 Z9 60 U1 2 U2 19 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD JUL PY 2011 VL 20 IS 7 BP 611 EP 617 DI 10.1136/bmjqs.2010.049379 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 778SX UT WOS:000291727100010 PM 21617166 ER PT J AU Nallapareddy, SR Sillanpaa, J Mitchell, J Singh, KV Chowdhury, SA Weinstock, GM Sullam, PM Murray, BE AF Nallapareddy, Sreedhar R. Sillanpaeae, Jouko Mitchell, Jennifer Singh, Kavindra V. Chowdhury, Shahreen A. Weinstock, George M. Sullam, Paul M. Murray, Barbara E. TI Conservation of Ebp-Type Pilus Genes among Enterococci and Demonstration of Their Role in Adherence of Enterococcus faecalis to Human Platelets SO INFECTION AND IMMUNITY LA English DT Article ID EXTRACELLULAR-MATRIX PROTEINS; URINARY-TRACT-INFECTION; CLUMPING FACTOR-A; STREPTOCOCCUS-PYOGENES; STAPHYLOCOCCUS-AUREUS; BIOFILM FORMATION; COLLAGEN ADHESIN; FAECIUM ISOLATE; ENDOCARDITIS; BACTERIA AB Ebp are endocarditis- and biofilm-associated pili of Enterococcus faecalis that are also important in experimental urinary tract infections (UTIs). Our analyses, using available genomes, found that the ebp locus is unique to enterococci. In E. faecalis, the ebp locus is very highly conserved and only 1/473 E. faecalis isolates tested lacked ebpABC, while only 1.2% had the bee pilus locus. No other pilus-encoding operon was identified in 55 available genomes, indicating that the vast majority of E. faecalis strains (unlike Enterococcus faecium and streptococci) have a single pilus locus. Surface expression studies showed that Ebp pili were produced in vitro by 91/91 brain heart infusion (BHI) plus serum-grown E. faecalis isolates and that strain OG1RF expressed pili at even higher levels in rat endocarditis vegetations. However, Ebp expression was restricted to 30 to 72% of E. faecalis cells, consistent with a bistability mode of expression. We also evaluated E. faecalis interactions with human platelets and found that growth of E. faecalis in BHI plus serum significantly enhanced adherence to human platelets and that sortase deletion mutants (the Delta srtA, Delta bps, and Delta bps Delta srtA mutants) were markedly defective. Further studies identified that Ebp pili, but not the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) Ace and Fss2, mediate adherence of E. faecalis to platelets. Taken together, our data show that the immunogenic (in human endocarditis patients) and commonly expressed Ebp pili, which are known to be important for experimental endocarditis, are highly conserved and mediate adherence to platelets, suggesting that Ebp pili may be a reasonable immunotherapeutic target for prevention or possibly treatment of endocarditis caused by this species. C1 [Nallapareddy, Sreedhar R.; Sillanpaeae, Jouko; Singh, Kavindra V.; Chowdhury, Shahreen A.; Murray, Barbara E.] Univ Texas Med Sch, Div Infect Dis, Dept Internal Med, Houston, TX 77030 USA. [Nallapareddy, Sreedhar R.; Sillanpaeae, Jouko; Singh, Kavindra V.; Chowdhury, Shahreen A.; Murray, Barbara E.] Univ Texas Med Sch, Ctr Study Emerging & Reemerging Pathogens, Houston, TX 77030 USA. [Murray, Barbara E.] Univ Texas Med Sch, Dept Microbiol & Mol Genet, Houston, TX 77030 USA. [Mitchell, Jennifer] Univ Coll Dublin, Dublin 2, Ireland. [Weinstock, George M.] Washington Univ, Dept Genet, St Louis, MO 63108 USA. [Sullam, Paul M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Sullam, Paul M.] Univ Calif San Francisco, San Francisco, CA 94121 USA. RP Murray, BE (reprint author), Univ Texas Med Sch Houston, Div Infect Dis, Dept Internal Med, 6431 Fannin St,MSB 2-112, Houston, TX 77030 USA. EM bem.asst@uth.tmc.edu RI Weinstock, George/C-6314-2013 OI Weinstock, George/0000-0002-2997-4592 FU Division of Microbiology and Infectious Diseases, NIAID, National Institutes of Health (NIH) [R37 AI47923, R01 AI47923]; Department of Veteran Affairs; NIH [R01 AI041513, R01 AI057433] FX This work was supported by National Institutes of Health (NIH) grants R37 AI47923 and R01 AI47923 from the Division of Microbiology and Infectious Diseases, NIAID, to B.E.M. and the Department of Veteran Affairs and NIH grants R01 AI041513 and R01 AI057433 to P.M.S. NR 75 TC 23 Z9 25 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2011 VL 79 IS 7 BP 2911 EP 2920 DI 10.1128/IAI.00039-11 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 779OO UT WOS:000291788700044 PM 21502588 ER PT J AU Schuyler, CA Ta, NN Li, YC Lopes-Virella, MF Huang, Y AF Schuyler, Corinne A. Ta, Nga N. Li, Yanchun Lopes-Virella, Maria F. Huang, Yan TI Insulin treatment attenuates diabetes-increased atherosclerotic intimal lesions and matrix metalloproteinase 9 expression in apolipoprotein E-deficient mice SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; HIGH GLUCOSE; MATRIX METALLOPROTEINASES; CARDIOVASCULAR-DISEASE; MMP-1 EXPRESSION; GLYCEMIC CONTROL; RECEPTOR; PLAQUES; MACROPHAGES; MIGRATION AB Patients with diabetes mellitus have increased mortality and morbidity of cardiovascular diseases compared with nondiabetic patients. Although clinical studies have shown that effective glycemic control with insulin treatment in patients with type 1 diabetes is associated with reduced cardiovascular events, the underlying mechanisms have not been well understood. In this study, we treated diabetic apolipoprotein E-deficient (apoE(-/-)) mice with insulin for 20 weeks and studied the effect of insulin treatment on intimal lesion size and matrix metalloproteinase (MMP) 9 expression known to be involved in plaque destabilization. Results showed that insulin treatment, which effectively reduced plasma glucose level in diabetic mice, attenuated diabetes-increased intimal lesion size and significantly inhibited diabetes-increased MMP9 expression, but had no effect on tissue inhibitor of metalloproteinase 1 in atherosclerotic plaques. Furthermore, we observed that insulin treatment did not reduce diabetes-increased macrophage content but inhibited interleukin 6 expression, a stimulator for MMP expression. Taken together, this study has shown for the first time that insulin treatment in diabetic apoE(-/-) mice changes atherosclerotic lesions and gene expression to a state that favors plaque stability. Journal of Endocrinology (2011) 210, 37-46 C1 [Schuyler, Corinne A.; Lopes-Virella, Maria F.; Huang, Yan] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Ta, Nga N.; Li, Yanchun; Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29425 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU Department of Veterans Affairs; NIH [DE016353] FX This study was supported by a Merit Review Grant from the Department of Veterans Affairs and NIH grant DE016353 (to Y H). NR 38 TC 12 Z9 12 U1 1 U2 4 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JUL PY 2011 VL 210 IS 1 BP 37 EP 46 DI 10.1530/JOE-10-0420 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 777OY UT WOS:000291633800006 PM 21478228 ER PT J AU Eid, GM Entabi, F Watson, AR Zuckerbraun, BS Wilson, MA AF Eid, George Michel Entabi, Fateh Watson, Andrew R. Zuckerbraun, Brian S. Wilson, Mark A. TI Robotic-Assisted Laparoscopic Side-to-Side Lateral Pancreaticojejunostomy SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Puestow; Pancreaticojejunostomy; Robotic C1 [Eid, George Michel] Minimally Invas Surg Ctr, Pittsburgh, PA 15213 USA. [Eid, George Michel; Entabi, Fateh; Watson, Andrew R.; Zuckerbraun, Brian S.; Wilson, Mark A.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Eid, George Michel; Wilson, Mark A.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Eid, GM (reprint author), Minimally Invas Surg Ctr, Suite 390,3380 Blvd Allies, Pittsburgh, PA 15213 USA. EM eidgm@upmc.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JUL PY 2011 VL 15 IS 7 BP 1243 EP 1243 DI 10.1007/s11605-011-1495-9 PG 1 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 778JU UT WOS:000291700800027 PM 21584825 ER PT J AU Humphrey, LL Shannon, J Partin, MR O'Malley, J Chen, ZQ Helfand, M AF Humphrey, Linda L. Shannon, Jackilen Partin, Melissa R. O'Malley, Jean Chen, Zunqiu Helfand, Mark TI Improving the Follow-Up of Positive Hemoccult Screening Tests: An Electronic Intervention SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE colorectal cancer; cancer screening; cancer prevention ID FECAL-OCCULT-BLOOD; COLORECTAL-CANCER; NOTIFICATION; MORTALITY; QUALITY; CARE; US AB BACKGROUND: Four population-based studies of screening for CRC with fecal occult blood testing (FOBT) have shown that mortality can be significantly reduced. However, nearly half of all positive screening tests are not appropriately evaluated. OBJECTIVES: We evaluated whether an electronic record intervention improved the follow-up of patients with a positive FOBT (FOBT+) result. DESIGN: We conducted a cluster randomized trial involving four Veteran's Affairs (VA) medical centers pair-matched by colonoscopy volume and randomized within the pair to receive the electronic intervention or usual care. PARTICIPANTS: All patients with FOBT+ results at participating facilities during a matched pre- and post-intervention time period. INTERVENTIONS: In the two intervention sites, an electronic consult that imported relevant clinical information was automatically submitted to the gastroenterology (GI) clinic for all FOBT+ patients at the time the result was recorded in the laboratory. In both intervention and control sites (usual care), PCPs continued to be notified of FOBT+ results in the usual manner MEASURES: Pre- and post-intervention changes in the proportion of FOBT+ patients having: (1) a GI consult or (2) a GI consult plus complete diagnostic evaluation (CDE) of the colon within 30, 90 and 180 days were compared across intervention and control sites. Log rank tests were used to determine statistical significance. RESULTS: The 30-, 90- and 180-day GI consult rates improved 21-33 % (p < 0.001) among intervention sites, but did not change in the usual care sites. Thirty-, 90- and 180-day CDE rates improved 9-31% (p < 0.03) in intervention sites, but did not significantly change in the usual care sites. Time to GI consult and CDE decreased significantly over time in the intervention sites (p < 0.001), but remained unchanged in the usual care sites. CONCLUSIONS: The relatively simple electronic intervention evaluated can significantly improve the follow-up of FOBT+ results. Interventions such as this could improve patient care and may be applicable to other practice settings, as well as other types of tests. C1 [Humphrey, Linda L.; Shannon, Jackilen; Helfand, Mark] Portland VA Med Ctr, Portland, OR 97239 USA. [Humphrey, Linda L.; Helfand, Mark] Oregon Hlth & Sci Univ, Dept Informat & Clin Epidemiol, Portland, OR 97201 USA. [Humphrey, Linda L.; Helfand, Mark] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Humphrey, Linda L.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Partin, Melissa R.] Minneapolis Vet Affairs Med Ctr, Minneapolis, MN USA. [O'Malley, Jean; Chen, Zunqiu] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Ctr, Portland, OR 97201 USA. RP Humphrey, LL (reprint author), Portland VA Med Ctr, Mail Code P-3 Med,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Linda.Humphrey@va.gov FU VA HSRD [CRT-02-059]; Oregon Clinical and Translational Research Institute (OCTRI); National Center for Research Resources (NCRR), National Institutes of Health (NIH) [UL1 RR024140 01]; NIH Roadmap for Medical Research FX This research was funded by VA HSR&D grant number CRT-02-059. This publication was made possible with support from the Oregon Clinical and Translational Research Institute (OCTRI); grant number UL1 RR024140 01 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH); and NIH Roadmap for Medical Research. The funding organizations had no direct involvement in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. We are grateful for the help of Barbara Genovese, MS; Courtney Maxcy, BS; Paige Farris, MSW; David Pauly, MBA, MSW; David Lieberman, MD; Joan Ash, PhD; Robert Socherman PhD; David Douglas, MD; and Michele Freeman, MPH, in the completion of this study and manuscript. We also acknowledge the help of the many co-investigators and programming staff involved with this study at each of the participating sites. NR 22 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2011 VL 26 IS 7 BP 691 EP 697 DI 10.1007/s11606-011-1639-3 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 778JY UT WOS:000291701200006 PM 21327529 ER PT J AU Lembke, A Bradley, KA Henderson, P Moos, R Harris, AHS AF Lembke, Anna Bradley, Katharine A. Henderson, Patricia Moos, Rudolf Harris, Alex H. S. TI Alcohol Screening Scores and the Risk of New-Onset Gastrointestinal Illness or Related Hospitalization SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE alcohol; AUDIT; gastrointestinal; hospitalization; new-onset; women ID IDENTIFICATION TEST AUDIT; USE DISORDERS; GENERAL-POPULATION; VETERANS-AFFAIRS; PRIMARY-CARE; DRINKING; QUESTIONNAIRES; CONSUMPTION; MORTALITY; SERVICES AB BACKGROUND: Excessive alcohol use is associated with a variety of negative health outcomes, including liver disease, upper gastrointestinal bleeding, and pancreatitis. OBJECTIVE: To determine the 2-year risk of gastrointestinal-related hospitalization and new-onset gastrointestinal illness based on alcohol screening scores. DESIGN: Retrospective cohort study. PARTICIPANTS: Male (N = 215, 924) and female (N = 9,168) outpatients who returned mailed questionnaires and were followed for 24 months. MEASUREMENTS: Alcohol Use Disorder Identification Test-Consumption Questionnaire (AUDIT-C), a validated three-item alcohol screening questionnaire (0-12 points). RESULTS: Two-year risk of hospitalization with a gastrointestinal disorder was increased in men with AUDIT-C scores of 5-8 and 9-12 (OR 1.54, 95% CI = 1.27-1.86; and OR 3.27; 95% CI = 2.62-4.09 respectively), and women with AUDIT-C scores of 9-12 (OR 6.84, 95% CI = 1.85 - 25.37). Men with AUDIT-C scores of 5-8 and 9-12 had increased risk of new-onset liver disease (OR 1.49, 95% CI = 1.30-1.71; and OR 2.82, 95% CI = 2.38-3.34 respectively), and new-onset of upper gastrointestinal bleeding (OR 1.28, 95% CI = 1.05-1.57; and OR 2.14, 95% CI = 1.54-2.97 respectively). Two-year risk of new-onset pancreatitis in men with AUDIT -C scores 9-12 was also increased (OR 2.14; 95% CI = 1.54-2.97). CONCLUSIONS: Excessive alcohol use as determined by AUDIT-C is associated with 2-year increased risk of gastrointestinal-related hospitalization in men and women and new-onset liver disease, upper gastrointestinal bleeding, and pancreatitis in men. These results provide risk information that clinicians can use in evidence-based conversations with patients about their alcohol consumption. C1 [Lembke, Anna] Stanford Univ, Sch Med, Dept Psychiat, Palo Alto, CA 94305 USA. [Bradley, Katharine A.] Vet Affairs VA Puget Sound Hlth Care Syst, Grp Hlth Res Inst, Hlth Serv Res & Dev HSR&D NW Ctr Excellence, Seattle, WA USA. [Bradley, Katharine A.] Grp Hlth Cooperat Puget Sound, Dept Med, Hlth Serv, Seattle, WA 98121 USA. [Bradley, Katharine A.] VA Puget Sound, Seattle, WA USA. [Bradley, Katharine A.] Univ WA, Seattle, WA USA. [Henderson, Patricia; Moos, Rudolf; Harris, Alex H. S.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA. RP Lembke, A (reprint author), Stanford Univ, Sch Med, Dept Psychiat, 401 Quarry Rd, Palo Alto, CA 94305 USA. EM alembke@stanford.edu FU NIAAA [R03 AA016793-01]; VA Office of Quality and Performance FX This paper does not necessarily represent the views of the Department of Veterans Affairs, Stanford University, or University of Washington. This work was made possible through a grant from NIAAA (R03 AA016793-01) and support from the VA Office of Quality and Performance. NR 25 TC 13 Z9 13 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2011 VL 26 IS 7 BP 777 EP 782 DI 10.1007/s11606-011-1688-7 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 778JY UT WOS:000291701200019 PM 21455813 ER PT J AU Hausmann, LRM Hannon, MJ Kresevic, DM Hanusa, BH Kwoh, CK Ibrahim, SA AF Hausmann, Leslie R. M. Hannon, Michael J. Kresevic, Denise M. Hanusa, Barbara H. Kwoh, C. Kent Ibrahim, Said A. TI Impact of Perceived Discrimination in Healthcare on Patient-Provider Communication SO MEDICAL CARE LA English DT Article DE social discrimination; communication; physician patient relations; minority health; Veterans health ID INTERACTION ANALYSIS SYSTEM; QUALITY-OF-CARE; AFRICAN-AMERICAN; PHYSICIANS COMMUNICATION; COMMUNITY SAMPLE; RACIAL BIAS; RACE; ASSOCIATION; PERCEPTIONS; DISPARITIES AB Background: The impact of patients' perceptions of discrimination in healthcare on patient-provider interactions is unknown. Objective: To examine association of past perceived discrimination with subsequent patient-provider communication. Research Design: Observational cross-sectional study. Subjects: African-American (N = 100) and white (N = 253) patients treated for osteoarthritis by orthopedic surgeons (N = 63) in 2 Veterans Affairs facilities. Measures: Patients were surveyed about past experiences with racism and classism in healthcare settings before a clinic visit. Visits were audio-recorded and coded for instrumental and affective communication content (biomedical exchange, psychosocial exchange, rapport-building, and patient engagement/activation) and nonverbal affective tone. After the encounter, patients rated visit informativeness, provider warmth/respectfulness, and ease of communicating with the provider. Regression models stratified by patient race assessed the associations of racism and classism with communication outcomes. Results: Perceived racism and classism were reported by more African-American patients than by white patients (racism: 70% vs. 26% and classism: 73% vs. 53%). High levels of perceived racism among African-American patients was associated with less positive nonverbal affect among patients [beta = -0.41, 95% confidence interval (CI) = -0.73 to -0.09] and providers (beta = -0.34, 95% CI = -0.66 to -0.01) and with low patient ratings of provider warmth/respectfulness [odds ratio (OR) = 0.19, 95% CI = 0.05-0.72] and ease of communication (OR = 0.22, 95% CI = 0.07-0.67). Any perceived racism among white patients was associated with less psychosocial communication (beta = -4.18, 95% CI = -7.68 to -0.68), and with low patient ratings of visit informativeness (OR = 0.40, 95% CI = 0.23-0.71) and ease of communication (OR = 0.43, 95% CI = 0.20-0.89). Perceived classism yielded similar results. Conclusions: Perceptions of past racism and classism in healthcare settings may negatively impact the affective tone of subsequent patient-provider communication. C1 [Hausmann, Leslie R. M.; Hannon, Michael J.; Hanusa, Barbara H.; Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hausmann, Leslie R. M.; Hannon, Michael J.; Hanusa, Barbara H.; Kwoh, C. Kent] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kresevic, Denise M.] Univ Hosp Case Med Ctr, Louis Stokes DVA Med Ctr, Cleveland, OH USA. [Ibrahim, Said A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ibrahim, Said A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Hausmann, LRM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. EM leslie.hausmann@gmail.com FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service [IIR 04-137]; Veterans Affairs Health Services [RCD 06-287, ER 0280-1]; National Institutes of Musculoskeletal and Skin Disorders [1K24AR055259-01] FX This study was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service (IIR 04-137, PI: Said A. Ibrahim). Dr. Hausmann's effort was supported by the Veterans Affairs Health Services Research and Development Career Development Program (RCD 06-287 and ER 0280-1). Dr. Ibrahim was also supported by a K24 Award (1K24AR055259-01) from the National Institutes of Musculoskeletal and Skin Disorders. The views expressed here are those of the authors and do not represent those of the Department of Veterans Affairs or the United States Government. NR 46 TC 32 Z9 34 U1 2 U2 14 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 JUL PY 2011 VL 49 IS 7 BP 626 EP 633 DI 10.1097/MLR.0b013e318215d93c PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 778VC UT WOS:000291735100003 PM 21478769 ER PT J AU Samal, L Saha, S Chander, G Korthuis, PT Sharma, RK Sharp, V Cohn, J Moore, RD Beach, MC AF Samal, Lipika Saha, Somnath Chander, Geetanjali Korthuis, P. Todd Sharma, Rashmi K. Sharp, Victoria Cohn, Jonathan Moore, Richard D. Beach, Mary Catherine TI Internet Health Information Seeking Behavior and Antiretroviral Adherence in Persons Living with HIV/AIDS SO AIDS PATIENT CARE AND STDS LA English DT Article ID UNITED-STATES; HIV; CARE; INTERVENTION; PATIENTSLIKEME; COMMUNICATION; INFECTION; COMMUNITY; IMPACT; ADULTS AB While the Internet has the potential to educate persons living with HIV/AIDS (PLWHA), websites may contain inaccurate information and increase the risk of nonadherence with antiretroviral therapy (ART). The objectives of our study were to determine the extent to which PLWHA engage in Internet health information seeking behavior (IHISB) and to determine whether IHISB is associated with ART adherence. We conducted a survey of adult, English-speaking HIV-infected patients at four HIV outpatient clinic sites in the United States (Baltimore, Maryland; Detroit, Michigan; New York, and Portland, Oregon) between December 2004 and January 2006. We assessed IHISB by asking participants how much information they had received from the Internet since acquiring HIV. The main outcome was patient-reported ART adherence over the past three days. Data were available on IHISB for 433 patients, 334 of whom were on ART therapy. Patients had a mean age of 45 (standard error [SE] 0.45) years and were mostly male (66%), African American (58%), and had attained a high school degree (73%). Most (55%) reported no IHISB, 18% reported some, and 27% reported "a fair amount" or "a great deal." Patients who reported higher versus lower levels of IHISB were significantly younger, had achieved a higher level of education, and had higher medication self-efficacy. In unadjusted analyses, higher IHISB was associated with ART adherence (odds ratio [OR], 2.96, 95% confidence interval [CI] 1.27-6.94). This association persisted after adjustment for age, gender, race, education, clinic site, and medication self-efficacy (adjusted odds ratio [AOR] 2.76, 95% CI 1.11-6.87). Our findings indicate that IHISB is positively associated with ART adherence even after controlling for potentially confounding variables. Future studies should investigate the ways in which Internet health information may promote medication adherence among PLWHA. C1 [Samal, Lipika] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. [Saha, Somnath] Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR USA. [Saha, Somnath] Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA. [Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Chander, Geetanjali; Moore, Richard D.; Beach, Mary Catherine] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA. [Sharma, Rashmi K.] Northwestern Univ, Div Hosp Med, Chicago, IL 60611 USA. [Sharp, Victoria] St Lukes Roosevelt Hosp, HIV Ctr Comprehens Care, New York, NY 10025 USA. [Cohn, Jonathan] Wayne State Univ, Div Infect Dis, Detroit, MI USA. RP Samal, L (reprint author), 1620 Tremont St,Suite BC 003-002V, Boston, MA 02120 USA. EM LSAMAL@PARTNERS.ORG FU Health Resources and Service Administration; Agency for Healthcare Research and Quality [AHRQ 290-01-0012, K08 HS013903-05]; National Institute of Drug Abuse [K23 DA019809]; National Institute on Alcoholism and Alcohol Abuse [K23 AA015313]; Department of Veterans Affairs; Robert Wood Johnson Generalist Physician Faculty Scholars Awards FX This research was supported by a contract from the Health Resources and Service Administration and the Agency for Healthcare Research and Quality (AHRQ 290-01-0012). Dr. Korthuis was supported by the National Institute of Drug Abuse (K23 DA019809), Dr. Chander was supported by the National Institute on Alcoholism and Alcohol Abuse (K23 AA015313), Dr. Saha was supported by the Department of Veterans Affairs, Dr. Beach was supported by the Agency for Healthcare Research and Quality (K08 HS013903-05) and both Drs. Beach and Saha were supported by Robert Wood Johnson Generalist Physician Faculty Scholars Awards. NR 33 TC 18 Z9 18 U1 2 U2 14 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 JUL PY 2011 VL 25 IS 7 BP 445 EP 449 DI 10.1089/apc.2011.0027 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 784DW UT WOS:000292135900008 PM 21682586 ER PT J AU West, RK Beeri, MS Schmeidler, J Mitchell, DB Carlisle, KR Angelo, G Mavris, R Langhoff, E Rosendorff, C Silverman, JM AF West, Rebecca K. Beeri, Michal Schnaider Schmeidler, James Mitchell, Dara B. Carlisle, Katherine R. Angelo, Gary Mavris, Rizalina Langhoff, Erik Rosendorff, Clive Silverman, Jeremy M. TI Homocysteine and Cognitive Function in Very Elderly Nondemented Subjects SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Cognitive performance; dementia; homocysteine ID ALZHEIMER-DISEASE; DECLINE; DEMENTIA; RISK; AGE AB Objectives: To examine the association of homocysteine with cognitive functioning in very elderly community-dwelling individuals (80 years or older). Methods: Two hundred twenty-eight nondemented community-dwelling individuals were assessed with a broad neuropsychological battery. Bloods were drawn to measure homocysteine, serum vitamin B(12), and folate levels and APOE genotype. Results: Higher homocysteine levels were associated with poorer executive-language functioning scores (r = -0.311). The association persisted when serum B12 and folate levels were controlled for (r = -0.308). Homocysteine levels were not associated with memory score (r = 0.120). Conclusions: In very elderly, nondemented community dwellers, high homocysteine levels are associated with poorer executive-language functioning but not with memory. This possible differential effect of homocysteine on cognitive functions suggests that it may affect only specific brain regions or mechanisms underlying healthy executive functioning. (Am J Geriatr Psychiatry 2011; 19:673-677) C1 [West, Rebecca K.; Beeri, Michal Schnaider; Schmeidler, James; Mitchell, Dara B.; Carlisle, Katherine R.; Angelo, Gary; Langhoff, Erik; Rosendorff, Clive; Silverman, Jeremy M.] Mt Sinai Sch Med, New York, NY USA. [Mavris, Rizalina; Langhoff, Erik; Rosendorff, Clive; Silverman, Jeremy M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP West, RK (reprint author), 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM rebecca.west@mssm.edu RI Yue, Chunlin/B-3554-2014 OI Yue, Chunlin/0000-0002-2261-6725 FU National Institutes of Health [AG002219, AG023515]; United States Department of Veterans Affairs, Berkman Charitable Trust FX This study was supported by National Institutes of Health (AG002219 [to JMS] and AG023515 [to MSB]) and United States Department of Veterans Affairs, Berkman Charitable Trust (to Vahram Haroutunian). NR 12 TC 8 Z9 8 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUL PY 2011 VL 19 IS 7 BP 673 EP 677 DI 10.1097/JGP.0b013e3181faee37 PG 5 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 782SQ UT WOS:000292031900009 PM 21709613 ER PT J AU Madero, M Wassel, CL Peralta, CA Najjar, SS Sutton-Tyrrell, K Fried, LF de Boer, IH Shlipak, MG Newman, AB Hausmann, D Sarnak, MJ Kritcheysky, SB Ix, JH AF Madero, Magdalena Wassel, Christina L. Peralta, Carmen A. Najjar, Samer S. Sutton-Tyrrell, Kim Fried, Linda F. de Boer, Ian H. Shlipak, Michael G. Newman, Anne B. Hausmann, Dorothy Sarnak, Mark J. Kritcheysky, Stephen B. Ix, Joachim H. CA Hlth ABC Study TI Markers of Mineral Metabolism Are Not Associated With Aortic Pulse Wave Velocity in Community-Living Elderly Persons: The Health Aging and Body Composition Study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE arterial stiffness; blood pressure; cardiovascular disease; hypertension; kidney disease; mineral metabolism; PWV ID SERUM PHOSPHORUS LEVELS; VITAMIN-D DEFICIENCY; PARATHYROID-HORMONE; CARDIOVASCULAR-DISEASE; 25-HYDROXYVITAMIN-D LEVELS; ARTERIAL STIFFNESS; MORTALITY RISK; RENAL-FUNCTION; YOUNG-ADULTS; CYSTATIN-C AB BACKGROUND Disorders in mineral metabolism are associated with risk for cardiovascular disease (CVD) events in patients with kidney disease as well as in the general population. This risk is thought to be mediated, in part, through the mechanism of stiffening of the arteries. METHODS The objective of this study was to evaluate the relationships between serum calcium, phosphorus, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D levels and arterial pulse wave velocity (aPWV) among 2,229 community-dwelling elderly persons participating in the Health Aging and Body Composition (Health ABC) study. RESULTS The mean age of the participants was 72 years; 52% were woman, 39% were black, and 17% had chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)). In parallel unadjusted analyses, the following associations were observed: 2.86% greater aPWV per 12 ng/ml (s.d.) lower 25-hydroxyvitamin D (95% confidence interval -4.38%, -1.31%), 3.04% greater aPWV per 28 pg/ml (s.d.) higher iPTH (95% confidence interval 1.42-4.68%), and 2.37% lower aPWV per 0.5 mg/dl (s.d.) higher phosphorus (95% confidence interval -3.90% to -0.81%). Except for phosphorus, these associations were attenuated and rendered no longer statistically significant after adjustment for demographic risk factors, clinical site, season, medications and other CVD risk factors. The results were similar in men and women and were not dependent on the presence of CKD. CONCLUSIONS Among well-functioning community-dwelling elderly persons, only serum phosphorus was associated with aPWV; and this association was in the opposite direction of the one hypothesized. Factors other than vascular stiffening may mediate the relationship between disordered mineral metabolism and CVD events in community-living elders. C1 [Madero, Magdalena] Inst Nacl Cardiol Ignacio Chavez, Dept Nephrol, Mexico City, DF, Mexico. [Wassel, Christina L.] Univ Calif San Diego, Div Prevent Med, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Peralta, Carmen A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Peralta, Carmen A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Najjar, Samer S.] Washington Hosp Ctr, MedStar Hlth Res Inst, Washington, DC 20010 USA. [Sutton-Tyrrell, Kim; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Fried, Linda F.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [de Boer, Ian H.] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [de Boer, Ian H.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Sect Gen Internal Med, San Francisco, CA USA. [Hausmann, Dorothy] Univ Georgia, Dept Foods & Nutr, Athens, GA 30602 USA. [Sarnak, Mark J.] Tufts Med Ctr, Dept Med, Div Nephrol, Boston, MA USA. [Kritcheysky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, San Diego, CA 92103 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Ctr, San Diego, CA USA. RP Madero, M (reprint author), Inst Nacl Cardiol Ignacio Chavez, Dept Nephrol, Mexico City, DF, Mexico. EM madero.magdalena@gmail.com RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU NIH, National Institute on Aging [R01 HL096851, R01 AG029364, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] FX This work was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (National Institute on Aging R01 HL096851, R01 AG029364, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106). NR 33 TC 8 Z9 8 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JUL PY 2011 VL 24 IS 7 BP 755 EP 761 DI 10.1038/ajh.2011.43 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 780ZT UT WOS:000291901100007 PM 21436791 ER PT J AU Luo, NL Wang, XD Chung, BH Lee, MH Klein, RL Garvey, WT Fu, YC AF Luo, Nanlan Wang, Xiangdong Chung, B. Hong Lee, Mi-Hye Klein, Richard L. Garvey, W. Timothy Fu, Yuchang TI Effects of macrophage-specific adiponectin expression on lipid metabolism in vivo SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE metabolic disorder; type 2 diabetes; atherosclerosis ID HIGH-DENSITY-LIPOPROTEIN; REVERSE CHOLESTEROL TRANSPORT; MONOCYTE-DERIVED MACROPHAGES; PIMA INDIAN POPULATION; INSULIN-RESISTANCE; ADIPOSE-TISSUE; SERUM ADIPONECTIN; LIVER-TRANSPLANTATION; APOLIPOPROTEIN-B; PLASMA-PROTEIN AB Luo N, Wang X, Chung BH, Lee M, Klein RL, Garvey WT, Fu Y. Effects of macrophage-specific adiponectin expression on lipid metabolism in vivo. Am J Physiol Endocrinol Metab 301: E180-E186, 2011. First published April 19, 2011; doi: 10.1152/ajpendo.00614.2010.-Epidemiological studies have associated low circulating levels of the adipokine adiponectin with multiple metabolic disorders, including metabolic syndrome, obesity, insulin resistance, type II diabetes, and cardiovascular disease. Recently, we reported that adiponectin selectively overexpressed in mouse macrophages can improve insulin sensitivity and protect against inflammation and atherosclerosis. To further investigate the role of adiponectin and macrophages on lipid and lipometabolism in vivo, we engineered the expression of adiponectin in mouse macrophages (Ad-TG mice) and examined effects on plasma lipoproteins and on the expression levels of genes involved in lipoprotein metabolism in tissues. Compared with the wild-type (WT) mice, Ad-TG mice exhibited significantly lower levels of plasma total cholesterol (-21%, P < 0.05) due to significantly decreased LDL (-34%, P < 0.05) and VLDL (-32%, P < 0.05) cholesterol concentrations together with a significant increase in HDL cholesterol (+41%, P < 0.05). Further studies investigating potential mechanisms responsible for the change in lipoprotein cholesterol profile revealed that adiponectin-producing macrophages altered expression of key genes in liver tissue, including apoA1, apoB, apoE, the LDL receptor, (P < 0.05), and ATP-binding cassette G1 (P < 0.01). In addition, Ad-TG mice also exhibited higher total and high-molecular-weight adipnection levels in plasma and increased expression of the anti-inflammatory cytokine IL-10 as well as a decrease in the proinflammatory cytokine IL-6 in adipose tissue. These results indicate that macrophages engineered to produce adiponectin can influence in vivo gene expression in adipose tissue in a manner that reduces inflammation and macrophage infiltration and in liver tissue in a manner that alters the circulating lipoprotein profile, resulting in a decrease in VLDL and LDL and an increase in HDL cholesterol. The data support further study addressing the use of genetically manipulated macrophages as a novel therapeutic approach for treatment of cardiometabolic disease. C1 [Luo, Nanlan; Chung, B. Hong; Garvey, W. Timothy; Fu, Yuchang] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Wang, Xiangdong] Shandong Univ, Sch Med, Inst Cell Biol, Jinan 250100, Peoples R China. [Lee, Mi-Hye; Klein, Richard L.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Lee, Mi-Hye; Klein, Richard L.] Med Univ S Carolina, Ralph H Johnson Dept Veteran Affairs Med Ctr, Charleston, SC 29425 USA. RP Fu, YC (reprint author), Univ Alabama, Dept Nutr Sci, Shelby Bldg 1213,1825 Univ Blvd, Birmingham, AL 35294 USA. EM yfu@uab.edu RI e-, a/F-9947-2012 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK-083562, DK-038764]; Medical Research Service of the Department of Veterans Affairs; University of Alabama Birmingham Diabetes Research and Training Center; American Diabetes Association [1-07-RA-49]; University of Alabama at Birmingham Diabetes Research Center [DK-079626] FX This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK-083562, DK-038764) and the Merit Review Program of the Medical Research Service of the Department of Veterans Affairs to W. T. Garvey and R. L. Klein and by grants from the University of Alabama Birmingham Diabetes Research and Training Center and American Diabetes Association (1-07-RA-49) to Y. Fu. We further acknowledge the University of Alabama at Birmingham Diabetes Research Center (DK-079626) for research core support. NR 46 TC 12 Z9 12 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUL PY 2011 VL 301 IS 1 BP E180 EP E186 DI 10.1152/ajpendo.00614.2010 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 783MA UT WOS:000292085900020 PM 21505149 ER PT J AU Batki, SL Canfield, KM Ploutz-Snyder, R AF Batki, Steven L. Canfield, Kelly M. Ploutz-Snyder, Robert TI Psychiatric and Substance Use Disorders among Methadone Maintenance Patients with Chronic Hepatitis C Infection: Effects on Eligibility for Hepatitis C Treatment SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID OPIOID-DEPENDENT PATIENTS; INJECTION-DRUG USERS; INTERFERON-ALPHA; COOCCURRING DISORDERS; VIRUS-INFECTION; ABUSE TREATMENT; PUBLIC-HEALTH; PREVALENCE; COMORBIDITY; CARE AB We set out to describe the prevalence and severity of psychiatric and substance use disorders (SUDs) in methadone maintenance treatment (MMT) patients with chronic hepatitis C virus (HCV) infection and to measure the impact on HCV-treatment eligibility. Psychiatric disorders, SUDs, and HCV-treatment eligibility were assessed in 111 MMT patients prior to a controlled trial of HCV treatment. Lifetime and current diagnosis rates, respectively were.. any non-SUD Axis I disorder 82% and 57%, any mood disorder: 67% and 35%, any anxiety disorder: 63% and 22%, any psychotic disorder: 11% and 9%. Antisocial personality disorder was present in 40%. A total of 56% met criteria for current SUDs. A total of 66% received psychiatric medications prior to HCV treatment; over half were receiving antidepressants. Despite psychiatric and substance use comorbidity, only 15% of patients were ineligible for HCV treatment: 10% clue to failure to complete the evaluation, and 5% due to psychiatric severity. Substance use did not lead to ineligibility in any participant. Multiple logistic regression showed the Beck Depression Inventory contributed significantly to predicting HCV treatment eligibility. Most MMT patients were ineligible for HCV treatment despite current SUD and non-SUD diagnoses. Depression severity may be a more significant predictor of HCV treatment eligibility than is substance use. (Am J Addict 2011;20:312-318) C1 [Batki, Steven L.] UCSF, Addict Psychiat Res Program, Dept Psychiat, San Francisco VA Med Ctr 116P, San Francisco, CA 94121 USA. [Batki, Steven L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Canfield, Kelly M.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Ploutz-Snyder, Robert] Univ Space Res Assoc, Houston, TX USA. RP Batki, SL (reprint author), UCSF, Addict Psychiat Res Program, Dept Psychiat, San Francisco VA Med Ctr 116P, 4150 Clement St, San Francisco, CA 94121 USA. EM steven.batki@ucsf.edu FU NIDA NIH HHS [R01 DA016764-06, R01 DA016764, R01 DA 016764] NR 52 TC 9 Z9 9 U1 0 U2 5 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 JUL-AUG PY 2011 VL 20 IS 4 BP 312 EP 318 DI 10.1111/j.1521-0391.2011.00139.x PG 7 WC Substance Abuse SC Substance Abuse GA 781CT UT WOS:000291908900002 PM 21679262 ER PT J AU Meszaros, ZS Dimmock, JA Abdul-Malak, Y Ploutz-Snyder, R Batki, SL AF Meszaros, Zsuzsa Szombathyne Dimmock, Jacqueline A. Abdul-Malak, Ynesse Ploutz-Snyder, Robert Batki, Steven L. TI Alcohol Use Is Associated with Impaired Decision Making in Patients with Schizophrenia and Schizoaffective Disorder SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Batki, Steven L.] SUNY Upstate Med Univ, Dept Psychiat, UCSF Dept Psychiat, Syracuse, NY USA. [Batki, Steven L.] San Francisco VA Med Ctr, San Francisco, CA 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 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2011 VL 20 IS 4 MA 7 BP 376 EP 376 PG 1 WC Substance Abuse SC Substance Abuse GA 781CT UT WOS:000291908900016 ER PT J AU Lugea, A Waldron, RT French, SW Pandol, SJ AF Lugea, Aurelia Waldron, Richard T. French, Samuel W. Pandol, Stephen J. TI Drinking and driving pancreatitis Links between endoplasmic reticulum stress and autophagy SO AUTOPHAGY LA English DT Editorial Material DE acinar cell; alcohol abuse; pancreas; ERAD; UPR; XBP1 AB Alcohol abuse is the leading etiologic factor of pancreatitis, although many heavy drinkers do not develop pancreatic damage. Alcohol promotes pancreatitis through a combination of remote (e.g., increased gut permeability to bacterial products such as lipopolysaccharide) and more proximal effects (e.g., altered pancreatic cholinergic inputs), including oxidative damage at the level of the pancreatic acinar cell. Recent evidence indicates that alcohol exposure to rodents disturbs proteostasis in the exocrine pancreas, an effect counterbalanced by homeostatic processes that include both the unfolded protein response (UPR) and autophagy. A corollary to this notion is that pancreatitis results when adaptive responses are insufficiently robust to alleviate the cellular stress caused by alcohol. C1 [Lugea, Aurelia; Waldron, Richard T.; Pandol, Stephen J.] VA Greater Los Angeles Healthcare Syst, So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA USA. [Lugea, Aurelia; Waldron, Richard T.; Pandol, Stephen J.] Univ Calif Los Angeles, Los Angeles, CA USA. [French, Samuel W.] Harbor UCLA Med Ctr, Dept Pathol, Torrance, CA 90509 USA. RP Lugea, A (reprint author), VA Greater Los Angeles Healthcare Syst, So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA USA. EM alugea@ucla.edu FU NCCIH NIH HHS [1P01AT003960, P01 AT003960]; NIAAA NIH HHS [R01 AA019954, R21 AA016010, R21AA016010]; PHS HHS [P50-A11999] NR 0 TC 10 Z9 11 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD JUL PY 2011 VL 7 IS 7 BP 783 EP 785 DI 10.4161/auto.7.7.15594 PG 3 WC Cell Biology SC Cell Biology GA 786JA UT WOS:000292300600017 PM 21460613 ER PT J AU Fiedler, SE Carr, DW AF Fiedler, Sarah E. Carr, Daniel W. TI ROPN1, a Protein Kinase A-Like (R2D2) Protein, Regulates Sperm Motility SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR) CY 2011 CL Portland, OR SP Soc Study Reproduct C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2011 VL 85 SI SI MA 804 PG 1 WC Reproductive Biology SC Reproductive Biology GA 032VC UT WOS:000310746200193 ER PT J AU Devic, I Hwang, HJ Edgar, JS Izutsu, K Presland, R Pan, C Goodlett, DR Wang, Y Armaly, J Tumas, V Zabetian, CP Leverenz, JB Shi, M Zhang, J AF Devic, Ivana Hwang, HyeJin Edgar, John Scott Izutsu, Kenneth Presland, Richard Pan, Catherine Goodlett, David R. Wang, Yu Armaly, Jeff Tumas, Vitor Zabetian, Cyrus P. Leverenz, James B. Shi, Min Zhang, Jing TI Salivary alpha-synuclein and DJ-1: potential biomarkers for Parkinson's disease SO BRAIN LA English DT Letter ID CARDIAC SYMPATHETIC-NERVE; LEWY BODY DISEASE; DEGENERATION; PATHOLOGY; SYSTEM; SECRETION C1 [Devic, Ivana; Hwang, HyeJin; Pan, Catherine; Wang, Yu; Armaly, Jeff; Shi, Min; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Devic, Ivana; Izutsu, Kenneth; Presland, Richard] Univ Washington, Sch Dent, Dept Oral Biol, Seattle, WA 98195 USA. [Edgar, John Scott; Goodlett, David R.] Univ Washington, Sch Pharm, Dept Med Chem, Seattle, WA 98195 USA. [Presland, Richard] Univ Washington, Sch Med, Dept Med Dermatol, Seattle, WA 98104 USA. [Wang, Yu] Huazhong Univ Sci & Technol, Dept Neurosurg, Tongji Hosp, Tongji Med Coll, Wuhan 430074, Peoples R China. [Tumas, Vitor] Univ Sao Paulo, Dept Neurosci & Behav, Ribeirao Preto Sch Med, BR-05508 Sao Paulo, Brazil. [Zabetian, Cyrus P.; Leverenz, James B.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98104 USA. [Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Leverenz, James B.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. RP Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, HMC Box 359635,325 9th Ave, Seattle, WA 98104 USA. EM zhangj@uw.edu RI Shi, Min/G-6165-2012; Tumas, Vitor/C-9949-2014 OI Shi, Min/0000-0002-6901-2558; FU NIA NIH HHS [AG033398, R01 AG033398]; NIDCR NIH HHS [DE17634]; NIEHS NIH HHS [ES004696, P42 ES004696]; NINDS NIH HHS [NS057567, NS062684, NS065070, P30 NS055088, P50 NS062684, P50 NS062684-02, R01 NS057567, R01 NS065070, R01 NS065070-02, R01 NS065070-03] NR 25 TC 66 Z9 69 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUL PY 2011 VL 134 AR e178 DI 10.1093/brain/awr015 PN 7 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 782YV UT WOS:000292049600001 PM 21349902 ER PT J AU Goldstein, NE May, CW Meier, DE AF Goldstein, Nathan E. May, Christopher W. Meier, Diane E. TI Comprehensive Care for Mechanical Circulatory Support A New Frontier for Synergy With Palliative Care SO CIRCULATION-HEART FAILURE LA English DT Article DE ventricular assist device; communication; palliative care; decision making; heart failure ID ADVANCED HEART-FAILURE; RANDOMIZED CONTROLLED-TRIAL; VENTRICULAR ASSIST DEVICE; INTERMACS ANNUAL-REPORT; OF-LIFE CARE; PROGNOSIS COMMUNICATION; ADVANCE DIRECTIVES; DECISION-MAKING; ADVANCED CANCER; END C1 [Goldstein, Nathan E.; Meier, Diane E.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Goldstein, Nathan E.] James J Peters Vet Affairs Med Ctr, GRECC, Bronx, NY USA. [May, Christopher W.] Inova Heart & Vasc Inst, Heart Failure Cardiac Transplant Program, Falls Church, VA USA. RP Goldstein, NE (reprint author), Mt Sinai Sch Med, Dept Geriatr & Palliat Med, Box 1070, New York, NY 10029 USA. EM Nathan.Goldstein@mssm.edu FU National Institute of Aging [K23 AG025933]; Mount Sinai Claude D Pepper Older Americans Independence Center from the National Institute on Aging [P30AG028741-01A2]; National Heart, Lung, and Blood Institute [1R01HL102084-01A1]; Greenwall Foundation; Kornfeld Program in Bioethics and Patient Care; National Cancer Institute [5R01CA116227] FX Dr Goldstein was supported by a Mentored Patient-Oriented Research Career Development Award for the National Institute of Aging (K23 AG025933), a grant from the Mount Sinai Claude D Pepper Older Americans Independence Center from the National Institute on Aging (P30AG028741-01A2), a grant from the National Heart, Lung, and Blood Institute (1R01HL102084-01A1), and a grant jointly provided by the Greenwall Foundation and the Kornfeld Program in Bioethics and Patient Care. Dr Meier was supported by a grant from the National Cancer Institute (5R01CA116227). NR 49 TC 20 Z9 20 U1 0 U2 2 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 JUL PY 2011 VL 4 IS 4 BP 519 EP + DI 10.1161/CIRCHEARTFAILURE.110.957241 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 794BX UT WOS:000292871300018 PM 21772016 ER PT J AU Lai, KKY Jin, M Yuan, S Larson, MF Dominitz, JA Bankson, DD AF Lai, Keane K. Y. Jin, Ming Yuan, Shan Larson, Meaghan F. Dominitz, Jason A. Bankson, Daniel D. TI Improved Reflexive Testing Algorithm for Hepatitis C Infection Using Signal-to-Cutoff Ratios of a Hepatitis C Virus Antibody Assay SO CLINICAL CHEMISTRY LA English DT Article ID UNITED-STATES; PREVALENCE AB BACKGROUND: Chemiluminescence immunoassay (CIA) is used to detect hepatitis C virus (HCV) antibody status on the basis of signal-to-cutoff (S/Co) ratios. Positive results of antibody to HCV (anti-HCV) are followed by either recombinant immunoblot assay (RIBA) to confirm anti-HCV positivity or reverse transcription (RT)-PCR to detect viremia. We hypothesized that by analyzing S/Co ratios, we could determine a strategy to reduce unnecessary supplementary testing in our population. METHODS: CIA was performed to screen for anti-HCV, and positive results were followed up with RT-PCR testing. Negative RT-PCR results were followed up with RIBA, whereas positive RT-PCR results were assumed to be RIBA positive. ROC curves were analyzed to determine the optimal S/Co ratios to predict HCV infection. RESULTS: We determined the S/Co ratios on 34 243 veteran patient samples. We found that with the CIA method 9.0% of patients had positive test results for anti-HCV. An S/Co ratio < 3.0 ruled out active HCV infection and exposure with 100% negative predictive value. When the S/Co ratio was >= 20.0, positive predictive values were 98.5% compared with RIBA results, and 81.0% compared with RT-PCR results. CONCLUSIONS: RIBA is not necessary to confirm negative or positive CIA anti-HCV if the S/Co ratio is < 3.0 or > 20.0, respectively. To confirm HCV exposure, samples with an S/Co ratio between 3.0 and 19.9 should be followed up with RIBA unless PCR testing has been performed and the result is positive. Samples with an S/Co ratio >= 20.0 or positive RIBA results should be further tested by RT-PCR to determine HCV viremia status. (C) 2011 American Association for Clinical Chemistry C1 [Jin, Ming] Temple Univ, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19140 USA. [Lai, Keane K. Y.] Univ So Calif, Dept Pathol, So Calif Res Ctr Alcohol Liver & Pancreat Dis & C, Los Angeles, CA 90089 USA. [Lai, Keane K. Y.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Yuan, Shan] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA. [Larson, Meaghan F.; Dominitz, Jason A.] Vet Affairs Puget Sound Hlth Care Syst, NW Hepatitis Resource Ctr C, Seattle, WA USA. [Dominitz, Jason A.] Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA USA. [Bankson, Daniel D.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Bankson, Daniel D.] Vet Affairs Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, Seattle, WA USA. RP Jin, M (reprint author), Temple Univ, Sch Med, Dept Pathol & Lab Med, 3401 N Broad St, Philadelphia, PA 19140 USA. EM mjin@temple.edu OI Dominitz, Jason/0000-0002-8070-7086 FU Department of Veterans Affairs; VAPSHCS Liver Research Enhancement Award Program; NIH [P50AA011999, T32AA007578] FX This material is based upon work supported by the National Hepatitis C Program, Department of Veterans Affairs. K.K.Y. Lai, VAPSHCS Liver Research Enhancement Award Program and NIH grants P50AA011999 and T32AA007578. NR 13 TC 13 Z9 13 U1 0 U2 5 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUL PY 2011 VL 57 IS 7 BP 1050 EP 1056 DI 10.1373/clinchem.2010.158691 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 784DL UT WOS:000292134400020 PM 21566071 ER PT J AU Li, YX Tafti, BA Shaba, W Berenji, GR AF Li, Yuxin Tafti, Bashir A. Shaba, Wisam Berenji, Gholam R. TI Extraosseus Uptake of F-18 Fluoride in the Primary Malignancy and Cerebral Metastasis in a Case of Non-Small-Cell Lung Cancer SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE F-18 fluoride; lung cancer; positron emission tomography; bone scan ID TC-99M MDP; CARCINOMA; TRACER; BREAST AB A 68-year-old man with history of heavy smoking was admitted for increasing falls during the past 4 weeks. Chest x-ray revealed a right upper lobe mass. Biopsy demonstrated poorly differentiated non-small-cell carcinoma. F-18 fluoride positron emission tomography/computer tomography (PET/CT) was performed to evaluate bone metastasis. Review of the sectional PET images demonstrated extraosseous fluoride uptake in the primary lung mass, as well as ring-shaped fluoride uptake in the cerebral metastatic lesion. Neither of these lesions demonstrated calcifications on CT images. The patient received radiation treatment of the brain metastasis after F-18 fluoride PET/CT study. C1 [Berenji, Gholam R.] VA Greater Los Angeles Healthcare Syst, Nucl Med Serv 115, Dept Nucl Med, Los Angeles, CA 90073 USA. RP Berenji, GR (reprint author), VA Greater Los Angeles Healthcare Syst, Nucl Med Serv 115, Dept Nucl Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Gholam.Berenji@va.gov NR 12 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD JUL PY 2011 VL 36 IS 7 BP 609 EP 611 DI 10.1097/RLU.0b013e318217af49 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 772XH UT WOS:000291271000035 PM 21637076 ER PT J AU Roshanaei-Moghaddam, B Pauly, MC Atkins, DC Baldwin, SA Stein, MB Roy-Byrne, P AF Roshanaei-Moghaddam, Babak Pauly, Michael C. Atkins, David C. Baldwin, Scott A. Stein, Murray B. Roy-Byrne, Peter TI RELATIVE EFFECTS OF CBT AND PHARMACOTHERAPY IN DEPRESSION VERSUS ANXIETY: IS MEDICATION SOMEWHAT BETTER FOR DEPRESSION, AND CBT SOMEWHAT BETTER FOR ANXIETY? SO DEPRESSION AND ANXIETY LA English DT Review DE meta-analysis; CBT; pharmacotherapy; depression; anxiety ID COGNITIVE-BEHAVIORAL THERAPY; PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; OBSESSIVE-COMPULSIVE DISORDER; GENERALIZED SOCIAL PHOBIA; COLLABORATIVE RESEARCH-PROGRAM; MENTAL-HEALTH TREATMENT; PANIC DISORDER; PRIMARY-CARE; ANTIDEPRESSANT MEDICATION AB Background: Little is known about whether cognitive behavioral therapy (CBT) or pharmacotherapy is relatively more advantageous for depressive versus anxiety disorders. Methods: We conducted a meta-analysis wherein we searched electronic databases and references to select randomized controlled studies comparing CBT and pharmacotherapy, with or without placebo, in adults with major depressive or anxiety disorders. The primary effect size was calculated from disorder-specific outcome measures as the difference between CBT and pharmacotherapy outcomes (i.e., positive effect size favors CBT; negative effect size favors pharmacotherapy). Results: Twenty-one anxiety (N = 1,266) and twenty-one depression (N = 2,027) studies comparing medication to CBT were included. Including all anxiety disorders, the overall effect size was .25 (95% CI: -0.02, 0.55, P = .07). Effects for panic disorder significantly favored CBT over medications (.50, 95% CI: 0.02, 0.98). Obsessive-compulsive disorder showed similar effects-sizes, though not statistically significant (.49, 95% CI: -0.11, 1.09). Medications showed a nonsignificant advantage for social anxiety disorder (-.22, 95% CI: -0.50, 0.06). The overall effect size for depression studies was .05 (95% CI: -0.09, 0.19), with no advantage for medications or CBT. Pooling anxiety disorder and depression studies, the omnibus comparison of the relative difference between anxiety and depression in effectiveness for CBT versus pharmacotherapy pointed to a nonsignificant advantage for CBT in anxiety versus depression (B = .14, 95% CI: -0.14, 0.43). Conclusions: On balance, the evidence presented here indicates that there are at most very modest differences in effects of CBT versus pharmacotherapy in the treatment of anxiety versus depressive disorders. There seems to be larger differences between the anxiety disorders in terms of their relative responsiveness to pharmacotherapy versus CBT. Depression and Anxiety 28: 560-567, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Roshanaei-Moghaddam, Babak; Pauly, Michael C.; Atkins, David C.; Baldwin, Scott A.; Stein, Murray B.; Roy-Byrne, Peter] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Roshanaei-Moghaddam, B (reprint author), VA Puget Sound Hlth Care Syst, S-116 ATC,1660 S Columbian Wy, Seattle, WA USA. EM babakr@uw.edu RI Baldwin, Scott/G-4021-2017 OI Baldwin, Scott/0000-0003-3428-0437; Atkins, David/0000-0002-5781-9880 NR 68 TC 34 Z9 36 U1 4 U2 46 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JUL PY 2011 VL 28 IS 7 BP 560 EP 567 DI 10.1002/da.20829 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 784JR UT WOS:000292153900002 PM 21608087 ER PT J AU Seal, KH Cohen, G Waldrop, A Cohen, BE Maguen, S Ren, L AF Seal, Karen H. Cohen, Greg Waldrop, Angela Cohen, Beth E. Maguen, Shira Ren, Li TI Substance use disorders in Iraq and Afghanistan veterans in VA healthcare, 2001-2010: Implications for screening, diagnosis and treatment SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcohol use disorders; Drug use disorders; Posttraumatic stress disorder; Comorbidity; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; COMORBIDITY SURVEY REPLICATION; ALCOHOL-RELATED PROBLEMS; MENTAL-HEALTH; VIETNAM VETERANS; SERVICE UTILIZATION; MILITARY PERSONNEL; COMBAT DEPLOYMENT; EXPOSURE THERAPY AB Background: The prevalence and correlates of alcohol use disorder (AUD) and drug use disorder (DUD) diagnoses in Iraq and Afghanistan veterans who are new users of Department of Veterans Affairs (VA) healthcare nationwide has not been evaluated. Methods: VA administrative data were used in retrospective cross-sectional descriptive and multivariable analyses to determine the prevalence and independent correlates of AUD and DUD in 456,502 Iraq and Afghanistan veterans who were first-time users of VA healthcare between October 15, 2001 and September 30, 2009 and followed through January 1, 2010. Results: Over 11% received substance use disorder diagnoses: AUD, DUD or both; 10% received AUD diagnoses, 5% received DUD diagnoses and 3% received both. Male sex, age <25 years, being never married or divorced, and proxies for greater combat exposure were independently associated with AUD and DUD diagnoses. Of those with AUD, DUD or both diagnoses, 55-75% also received PTSD or depression diagnoses. AUD, DUD or both diagnoses were 3-4.5 times more likely in veterans with PTSD and depression (p < 0.001). Conclusions: Post-deployment AUD and DUD diagnoses were more prevalent in subgroups of Iraq and Afghanistan veterans and were highly comorbid with PTSD and depression. Stigma and lack of universal screening may have reduced the number of DUD diagnoses reported. There is a need for improved screening and diagnosis of substance use disorders and increased availability of integrated treatments that simultaneously address AUD and DUD in the context of PTSD and other deployment-related mental health disorders. Published by Elsevier Ireland Ltd. C1 [Seal, Karen H.; Cohen, Greg; Waldrop, Angela; Cohen, Beth E.; Maguen, Shira; Ren, Li] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Seal, Karen H.; Waldrop, Angela; Cohen, Beth E.; Maguen, Shira] Univ Calif San Francisco, San Francisco, CA 94121 USA. RP Seal, KH (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 111A-1, San Francisco, CA 94121 USA. EM Karen.Seal@va.gov RI Schueter, nicos/A-3625-2014 FU VA Health Services Research and Development (HSRD); Department of Defense [W81XWH-05-2-0094]; VA HSR&D Career Development Award; San Francisco VA Medical Center; [K23 DA018718]; [K23 HL 094765-01] FX This study was funded by a VA Health Services Research and Development (HSR&D) Career Development Award and by a Department of Defense Award (W81XWH-05-2-0094). Dr. Waldrop was supported by a K23 DA018718. Dr. Cohen was supported by a K23 HL 094765-01. Dr. Maguen was supported by a VA HSR&D Career Development Award. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review or approval of the manuscript.; The authors wish to acknowledge the service and courage of the men and women who have served in Iraq, Afghanistan and surrounding areas. We also wish to acknowledge Mr. Daniel Bertenthal of the San Francisco VA Medical Center HSR&D Research Enhancement Award Program who provided consultation on the use of VA national-level data. NR 86 TC 114 Z9 114 U1 6 U2 19 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUL 1 PY 2011 VL 116 IS 1-3 BP 93 EP 101 DI 10.1016/j.drugalcdep.2010.11.027 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 784SY UT WOS:000292179700015 PM 21277712 ER PT J AU Banks, WA AF Banks, William A. TI Extrahypothalamic Effects of Leptin: A Therapeutic for Depression and Dementia? SO ENDOCRINOLOGY LA English DT Editorial Material ID HIGH-FAT DIET; RECEPTOR EXPRESSION; MEMORY C1 [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Banks, William A.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA 98108 USA. RP Banks, WA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Room 810A,Bldg 1,1660 S Columbian Way, Seattle, WA 98108 USA. EM wabanks1@uw.edu NR 14 TC 6 Z9 6 U1 0 U2 2 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 JUL PY 2011 VL 152 IS 7 BP 2539 EP 2541 DI 10.1210/en.2011-1161 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 781IZ UT WOS:000291925700001 PM 21697453 ER PT J AU Restrepo, MI Mortensen, EM Anzueto, A AF Restrepo, M. I. Mortensen, E. M. Anzueto, A. TI Are COPD patients with pneumonia who are taking inhaled corticosteroids at higher risk of dying? SO EUROPEAN RESPIRATORY JOURNAL LA English DT Editorial Material ID OBSTRUCTIVE PULMONARY-DISEASE; COMMUNITY-ACQUIRED PNEUMONIA; METERED-DOSE INHALER; SALMETEROL/FLUTICASONE PROPIONATE; CLINICAL-TRIAL; BUDESONIDE; EXACERBATIONS; PREVENTION; SALMETEROL; FORMOTEROL C1 [Restrepo, M. I.; Mortensen, E. M.] Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. [Restrepo, M. I.; Mortensen, E. M.; Anzueto, A.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Restrepo, M. I.; Anzueto, A.] Div Pulm & Crit Care Med, San Antonio, TX USA. [Mortensen, E. M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hosp Med, San Antonio, TX 78229 USA. RP Restrepo, MI (reprint author), S Texas Vet Hlth Care Syst ALMD, VERDICT 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 OI Mortensen, Eric/0000-0002-3880-5563 FU NHLBI NIH HHS [K23 HL096054, K23HL096054] NR 15 TC 7 Z9 7 U1 0 U2 3 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD JUL PY 2011 VL 38 IS 1 BP 1 EP 3 DI 10.1183/09031936.00028711 PG 3 WC Respiratory System SC Respiratory System GA 785RW UT WOS:000292247700001 PM 21719494 ER PT J AU Wang, Q Yan, JQ Chen, XH Li, J Yang, Y Weng, JP Deng, C Yenari, MA AF Wang, Qing Yan, Junqiang Chen, Xiaohong Li, Jin Yang, Yu Weng, JianPing Deng, Chao Yenari, Midori A. TI Statins: Multiple neuroprotective mechanisms in neurodegenerative diseases SO EXPERIMENTAL NEUROLOGY LA English DT Review DE Statins; Inflammation; Ischemia; Alzheimer's disease; Parkinson's disease; Neuroprotection ID NITRIC-OXIDE SYNTHASE; COA REDUCTASE INHIBITORS; CEREBRAL VASOMOTOR REACTIVITY; MILD COGNITIVE IMPAIRMENT; D-2 RECEPTOR EXPRESSION; BRAIN-BARRIER BREAKDOWN; SMOOTH-MUSCLE-CELLS; ALZHEIMERS-DISEASE; BLOOD-PRESSURE; PARKINSONS-DISEASE AB Statins have been widely used for the treatment of a variety of conditions beyond their original role in lowering cholesterol. Since statins have relatively few side effects, they have been recognized as useful medicine to ameliorate neurodegenerative disorders. Current studies on the applications of statins have demonstrated their neuroprotective and clinical significance among neurodegenerative diseases like cerebral ischemic stroke, vascular dementia, Alzheimer's disease, and Parkinson's disease, though the neuroprotective mechanisms are not completely understood. This review will discuss recent development in the use of statins in slowing down the progression of these neurodegenerative diseases. It will summarize the potential mechanisms for statin-mediated neuroprotective effects in neurodegenerative diseases. In detail, this review discuss the roles of statins in lowering cholesterol, reducing reactive oxygen species, impairing beta-amyloid production and serum apolipoprotein E levels, enhancing the levels of endothelial nitric oxide synthase and cerebral blood flow, and modulating cognitive related receptors and matrix metalloproteases. Finally, different alterations of various receptors in brain regions following statin treatment and their correlations with cognitive dysfunction in Parkinson's disease will also be reviewed, as well as the potential for therapy in ameliorating the progression of Parkinson's disease. This article is part of a Special Issue entitled "Interaction between repair, disease, & inflammation." (C) 2010 Elsevier Inc. All rights reserved. C1 [Wang, Qing] Sun Yat Sen Univ, Affiliated Hosp 3, Neurol Res Lab, Dept Neurol, Guangzhou 510630, Guangdong, Peoples R China. [Weng, JianPing] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Endocrinol, Guangzhou 510630, Guangdong, Peoples R China. [Wang, Qing; Deng, Chao] Univ Wollongong, Sch Hlth Sci, Ctr Translat Neurosci, Wollongong, NSW 2522, Australia. [Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Wang, Q (reprint author), Sun Yat Sen Univ, Affiliated Hosp 3, Neurol Res Lab, Dept Neurol, 600 Tianhe Rd, Guangzhou 510630, Guangdong, Peoples R China. EM denniswq@yahoo.com RI Deng, Chao/F-4417-2016 OI Deng, Chao/0000-0003-1147-5741 FU Third Affiliated Hospital of Sun Yat-Sen University; Sun Yat-Sen University [A77, 10ykzd08]; Ministry of Education (PR China); Australia National Health and Medical Research Council (NHMRC) [514640] FX This work was supported by Grant-In-Aid of the Third Affiliated Hospital of Sun Yat-Sen University and Sun Yat-Sen University (grant no. A77 and 10ykzd08), Distinguished Young Investigator Supporting Grant of the Ministry of Education (PR China), and Australia National Health and Medical Research Council Grant (NHMRC, ID: 514640) from Q.W. We would like to thank Dr. Mandy Reid for critical reading of this manuscript. NR 116 TC 47 Z9 51 U1 1 U2 23 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 2011 VL 230 IS 1 SI SI BP 27 EP 34 DI 10.1016/j.expneurol.2010.04.006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 781BT UT WOS:000291906300004 PM 20406638 ER PT J AU Dubin, R Owens, C Gasper, W Ganz, P Johansen, K AF Dubin, Ruth Owens, Christopher Gasper, Warren Ganz, Peter Johansen, Kirsten TI Associations of endothelial dysfunction and arterial stiffness with intradialytic hypotension and hypertension SO HEMODIALYSIS INTERNATIONAL LA English DT Article DE Endothelial dysfunction; arterial stiffness; intradialytic hypotension; intradialytic hypertension; phosphorus ID HEMODIALYSIS-ASSOCIATED HYPOTENSION; STAGE RENAL-DISEASE; FLOW-MEDIATED DILATION; CHRONIC KIDNEY-DISEASE; ASYMMETRIC DIMETHYLARGININE; CARDIOVASCULAR EVENTS; OXIDATIVE STRESS; VITAMIN-E; DIALYSIS; FAILURE AB Intradialytic hypotension and hypertension are both independently associated with mortality among persons with end-stage renal disease on hemodialysis. Endothelial dysfunction and arterial stiffness are two possible mechanisms underlying these phenomena, but their association with hemodynamic instability during dialysis has not been evaluated. Thirty patients were recruited from chronic dialysis units at San Francisco General Hospital and San Francisco Veterans Affairs Medical Center. Endothelial dysfunction was assessed with flow-mediated dilation of the brachial artery after upper arm occlusion. Arterial stiffness was assessed using carotid-femoral pulse wave velocity measured by tonometry. Intradialytic hypotension and hypertension were defined as the average decrease in systolic blood pressure (SBP) over 1 week, as well as the frequency over 1 month of hypotension or hypertension. Every 5% decrease in flow-mediated dilation was associated with a 7.5 mmHg decrease in SBP after adjustment for phosphorus, body mass index, atherosclerosis, and ultrafiltration (P=0.02). Every 5 m/s increase in pulse wave velocity was associated with an 8 mmHg increase in SBP after adjustment for predialysis SBP and ultrafiltration (P=0.03). Over 1 month, every 5% lower flow-mediated dilation was associated with a 10% higher frequency of hypotension (P=0.09), and every 5 m/s increase in pulse wave velocity was associated with an 15% higher frequency of hypertension (P=0.02). In a cross-sectional analysis of 30 dialysis patients, endothelial dysfunction and arterial stiffness were independently associated with intradialytic hypotension and intradialytic hypertension, respectively. Elucidating these potential mechanisms of hemodynamic instability during dialysis may facilitate development of treatment strategies specific to this pathophysiology. C1 [Dubin, Ruth; Johansen, Kirsten] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA 94143 USA. [Owens, Christopher; Gasper, Warren] Univ Calif San Francisco, Dept Vasc & Endovasc Surg, San Francisco, CA 94143 USA. [Owens, Christopher; Johansen, Kirsten] San Francisco VA Med Ctr, San Francisco, CA USA. [Ganz, Peter] Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. RP Dubin, R (reprint author), Univ Calif San Francisco, Dept Med, Div Nephrol, 521 Parnassus Ave,C443, San Francisco, CA 94143 USA. EM ruth.dubin@ucsf.edu FU Clinical and Translational Science Institute, University of California, San Francisco FX This research is funded through the Clinical and Translational Science Institute by the Resource Allocation Program of the University of California, San Francisco. The authors have no conflicts of interest to declare. NR 48 TC 17 Z9 18 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1492-7535 J9 HEMODIAL INT JI Hemodial. Int. PD JUL PY 2011 VL 15 IS 3 BP 350 EP 358 DI 10.1111/j.1542-4758.2011.00560.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 786NJ UT WOS:000292314900008 PM 21658174 ER PT J AU Schillace, RV Miller, CL Carr, DW AF Schillace, Robynn V. Miller, Casey L. Carr, Daniel W. TI AKAPs in lipid rafts are required for optimal antigen presentation by dendritic cells SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Article DE AKAP; antigen presentation; human dendritic cell; lipid raft; signal transduction ID PROTEIN-KINASE-A; CLASS-II MOLECULES; MEMBRANE RAFTS; CYTOKINE PRODUCTION; KEY FACTOR; T-CELLS; EZRIN; ACTIVATION; RECEPTOR; MATURATION AB Dendritic cell (DC) maturation and antigen presentation are regulated by activation of protein kinase A (PKA) signaling pathways, through unknown mechanisms. We have recently shown that interfering with PKA signaling through the use of anchoring inhibitor peptides hinders antigen presentation and DC maturation. These experiments provide evidence that DC maturation and antigen presentation are regulated by A-kinase anchoring proteins (AKAPs). Herein, we determine that the presence of AKAPs and PKA in lipid rafts regulates antigen presentation. Using a combination of western blotting and immuno-cytochemistry, we illustrate the presence of AKAP149, AKAP79, Ezrin and the regulatory subunits of PKA in DC lipid rafts. Incubation of DCs with the type II anchoring inhibitor, AKAP-in silico (AKAP-IS), removes Ezrin and RII from the lipid raft without disrupting raft formation. Addition of a lipid raft disruptor, methyl-beta-cyclodextrin, blocks the efficacy of AKAP-IS, suggesting that the lipid raft must be intact for AKAP-IS to inhibit antigen presentation. Ezrin and AKAP79 are present in the lipid raft of stimulated KG1 cells, but Ezrin is not present in the lipid raft of unstimulated KG1 cells and AKAP79 levels are greatly diminished, suggesting that Ezrin and AKAP79 may be the key AKAPs responsible for regulating antigen presentation. Immunology and Cell Biology (2011) 89, 650-658; doi:10.1038/icb.2010.148; published online 11 January 2011 C1 [Schillace, Robynn V.; Miller, Casey L.; Carr, Daniel W.] Portland VA Med Ctr, Portland, OR 97239 USA. [Schillace, Robynn V.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Carr, Daniel W.] Oregon Hlth & Sci Univ, Dept Endocrinol, Portland, OR 97201 USA. RP Carr, DW (reprint author), Portland VA Med Ctr, VAMC RD 8,3710 US Vet Hosp Rd, Portland, OR 97239 USA. EM carrd@ohsu.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Service FX This research was supported by Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Service (DWC). We thank Sarah Fiedler and Dr Sonemany Salinthone for helpful comments during paper preparation. NR 51 TC 8 Z9 9 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD JUL PY 2011 VL 89 IS 5 BP 650 EP 658 DI 10.1038/icb.2010.148 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 786PK UT WOS:000292320200011 PM 21221125 ER PT J AU Mulligan, JK Mulligan, RM Atkinson, C Schlosser, RJ AF Mulligan, Jennifer K. Mulligan, Ryan M. Atkinson, Carl Schlosser, Rodney J. TI Human sinonasal epithelial cells direct dendritic function and T-cell T helper 1/T helper 2 skewing following Aspergillus exposure SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article; Proceedings Paper CT 69th Annual Meeting of the American-Academy-of-Otolaryngic-Allergy (AAOA) CY SEP 24-25, 2010 CL Boston, MA SP Amer Acad Otolaryng Allergy (AAOA) DE allergic fungal rhinosinusitis; chronic rhinosinusitis without nasal polyps; chronic rhinosinusitis; dendritic cells; human sinonasal epithelial cells ID CHRONIC RHINOSINUSITIS; NASAL POLYPOSIS; HOST-DEFENSE; ASTHMA; SINUSITIS; DISEASE; CYTOKINES; IMMUNITY; PERSPECTIVES; EXPRESSION AB Background: In lower airway disease such as asthma, epithelial cells have been shown to be potent regulators of dendritic cell (DC) functions. However, it is unclear how human sinonasal epithelial cells (HSNECs) from patients with sinusitis regulate DC functions. Therefore, in these studies we investigated the ability of Aspergillus fumigatus exposed HSNECs to regulate DC antigen uptake, maturation, and direction of T-cell T helper 1 (Th1)/Th2 skewing. Methods: Primary HSNECs were cultured from control (n = 8), chronic sinusitis without nasal polyps (CRSsNP) (n = 9), and chronic sinusitis with nasal polyps (CRSwNP) (n = 7) patients and exposed to Aspergillus. Conditioned media was placed upon monocyte-derived DCs from healthy controls. DC antigen uptake was assessed by dextran-fluorescein isothiocyanate (FITC) uptake. DC differentiation and maturation was assessed by immunostaining for CD209, CD80, and CD86 followed by flow cytometric analysis. DC direction of T-cell Th1/Th2 skewing was evaluated by immunostaining followed by intracellular flow cytometric analysis for interferon (IFN)-gamma and interleukin (IL)-5. Results: Control and CRSsNP HSNECs have the capacity to stimulate DC antigen uptake, differentiation, and maturation following Aspergillus exposure. CRSwNP HSNECs stimulate DC activation independent of Aspergillus exposure. Furthermore, Aspergillus-exposed CRSwNP HSNECs skew T-cells toward a Th2 phenotype. Conclusion: CRSwNP-derived HSNECs stimulate DC maturation and Th2 skewing independent of Aspergillus exposure. However, control and CRSsNP HSNECs induce DC maturation and Th2 skewing after Aspergillus exposure. These in vitro studies demonstrate that HSNECs are key regulators of DC functions in the sinus microenvironment. (C) 2011 ARS-AAOA, LLC. C1 [Mulligan, Jennifer K.; Mulligan, Ryan M.; Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Mulligan, Jennifer K.; Mulligan, Ryan M.; Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Atkinson, Carl] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Mulligan, JK (reprint author), MSC 550,135 Rutledge Ave, Charleston, SC 29425 USA. EM konopa@musc.edu NR 35 TC 9 Z9 9 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD JUL-AUG PY 2011 VL 1 IS 4 BP 268 EP 274 DI 10.1002/alr.20055 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 007XS UT WOS:000308922300007 PM 22287430 ER PT J AU Lockhart, SR Wagner, D Iqbal, N Pappas, PG Andes, DR Kauffman, CA Brumble, LM Hadley, S Walker, R Ito, JI Baddley, JW Chiller, T Park, BJ AF Lockhart, Shawn R. Wagner, Debra Iqbal, Naureen Pappas, Peter G. Andes, David R. Kauffman, Carol A. Brumble, Lisa M. Hadley, Susan Walker, Randall Ito, James I. Baddley, John W. Chiller, Tom Park, Benjamin J. TI Comparison of In Vitro Susceptibility Characteristics of Candida Species from Cases of Invasive Candidiasis in Solid Organ and Stem Cell Transplant Recipients: Transplant-Associated Infections Surveillance Network (TRANSNET), 2001 to 2006 SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GLOBAL ANTIFUNGAL SURVEILLANCE; BONE-MARROW-TRANSPLANTATION; STANDARDIZED DISK DIFFUSION; FUNGAL-INFECTIONS; IMMUNOCOMPROMISED PATIENTS; FLUCONAZOLE PROPHYLAXIS; ACTIVE SURVEILLANCE; UNITED-STATES; EPIDEMIOLOGY; KRUSEI AB Invasive fungal infections (IFI) are a major cause of morbidity and mortality among both solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Candida is the most common cause of IFI in SOT recipients and the second most common cause of IFI in HSCT recipients. We determined susceptibilities to fluconazole, voriconazole, itraconazole, posaconazole, amphotericin B, and caspofungin for 383 invasive Candida sp. isolates from SOT and HSCT recipients enrolled in the Transplant-Associated Infection Surveillance Network and correlated these results to clinical data. Fluconazole resistance in C. albicans, C. tropicalis, and C. parapsilosis isolates was low (1%), but the high percentage of C. glabrata and C. krusei isolates within this group of patients increased the overall percentage of fluconazole resistance to 16%. Voriconazole resistance was 3% overall but was 8% among C. glabrata isolates. On multivariable analysis, among HSCT recipients fluconazole nonsusceptibility was independently associated with C. glabrata, non-Hodgkin's lymphoma, cytomegalovirus (CMV) antigenemia, diabetes active at the time of the IFI, and any prior amphotericin B use; among SOT recipients, fluconazole nonsusceptibility was independently associated with any fluconazole use in the 3 months prior to the IFI, C. glabrata, ganciclovir use in the 3 months prior to the IFI, diabetes acquired since the transplant, and gender. C1 [Lockhart, Shawn R.; Wagner, Debra; Iqbal, Naureen; Chiller, Tom; Park, Benjamin J.] Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA 30333 USA. [Pappas, Peter G.; Baddley, John W.] Univ Alabama, Dept Med, Div Infect Dis & Prevent Med, Birmingham, AL 35294 USA. [Andes, David R.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Kauffman, Carol A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Kauffman, Carol A.] Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Brumble, Lisa M.] Mayo Clin, Jacksonville, FL 32224 USA. [Hadley, Susan] Tufts Med Ctr, Boston, MA USA. [Walker, Randall] Mayo Clin, Coll Med, Rochester, MN USA. [Ito, James I.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Dept Med, Div Infect Dis, Birmingham, AL USA. RP Lockhart, SR (reprint author), Ctr Dis Control & Prevent, Mycot Dis Branch, 1600 Clifton Rd NE,Mailstop G-11, Atlanta, GA 30333 USA. EM gyi2@cdc.gov FU Astellas; Pfizer; Merck; Schering-Plough FX TRANSNET was sponsored by Astellas, Pfizer, Merck, and Schering-Plough.; Potential conflicts of interest are as follows: P.G.P. receives research support from and is an ad hoc advisor for Merck, Pfizer, and Astellas; J.W.B. received research support from Pfizer and is a consultant/advisor for Merck and Pfizer; J.I.I. received honoraria for speaker activities from Astellas, Cubist, and Pfizer; D.R.A. has received grants from and is a consultant for Merck, Astellas, and Pfizer; and C.A.K. receives research support from Merck and chairs a data adjudication committee for Pfizer. All other authors have no conflicts. NR 34 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2011 VL 49 IS 7 BP 2404 EP 2410 DI 10.1128/JCM.02474-10 PG 7 WC Microbiology SC Microbiology GA 786BC UT WOS:000292276200004 PM 21562099 ER PT J AU Rhodes, KV Dichter, ME Kothari, CL Marcus, SC Cerulli, C AF Rhodes, Karin Verlaine Dichter, Melissa E. Kothari, Catherine L. Marcus, Steven C. Cerulli, Catherine TI The Impact of Children on Legal Actions Taken by Women Victims of Intimate Partner Violence SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE Intimate partner violence; Children; Prosecution; Personal protection order; Help seeking ID ABUSIVE RELATIONSHIPS; DECISION-MAKING; PROSECUTION; PROTECTION AB Successful criminal or civil legal system response to assaults against intimate partners (intimate partner violence; IPV) usually rely on the victim's participation in the legal process, including having contact with the prosecutor, filing charges, and/or applying for an order of personal protection. Using data abstracted from criminal and civil legal system records for a county-wide cohort of 990 female IPV victims over a 4-year period, we examine the impact of having children, and of specific child factors, on victims' engagement with the criminal prosecution of their abusive partners and/or seeking a personal protection order (PPO) in the civil court system. Having children increased victim's contact with the prosecutor and applications for PPOs, but did not increase her likelihood of wanting to file or drop charges. Findings support prior work suggesting both the importance and complexity of children on mothers' decision-making. Policy makers and service providers may want to assess survivors' thoughts about the role children play in their decision-making. Additionally, by offering survivors interventions to help their children address the impact of IPV exposure, survivors may be more willing to engage with services. C1 [Rhodes, Karin Verlaine] Univ Penn, Div Emergency Care Policy Res, Dept Emergency Med, Philadelphia, PA 19104 USA. [Rhodes, Karin Verlaine; Dichter, Melissa E.; Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Rhodes, Karin Verlaine] Univ Penn, Sch Med, Dept Emergency Med, Philadelphia, PA 19104 USA. [Dichter, Melissa E.; Marcus, Steven C.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Kothari, Catherine L.] Michigan State Univ, Kalamazoo Ctr Med Studies, Kalamazoo, MI USA. [Rhodes, Karin Verlaine; Marcus, Steven C.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Cerulli, Catherine] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. RP Rhodes, KV (reprint author), Univ Penn, Div Emergency Care Policy Res, Dept Emergency Med, 3815 Walnut St, Philadelphia, PA 19104 USA. EM kvr@sp2.upenn.edu OI Kothari, Catherine/0000-0001-8072-8920 NR 39 TC 8 Z9 8 U1 1 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD JUL PY 2011 VL 26 IS 5 BP 355 EP 364 DI 10.1007/s10896-011-9370-8 PG 10 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 782WY UT WOS:000292044600003 ER PT J AU Jordan, TH Talarico, RH Schuberth, JM AF Jordan, Thomas H. Talarico, Ross H. Schuberth, John M. TI The Radiographic Fate of the Syndesmosis after Trans-syndesmotic Screw Removal in Displaced Ankle Fractures SO JOURNAL OF FOOT & ANKLE SURGERY LA English DT Article DE ankle fracture; open reduction; syndesmosis ID DISTAL TIBIOFIBULAR SYNDESMOSIS; FIXATION; INSTABILITY; ROTATION; CADAVER; OSSIFICATION; BIMALLEOLAR; DIASTASIS; INJURIES; MODEL AB The purpose of this study was to evaluate the radiographic changes of the tibiofibular position and the ankle mortise after removal of trans-syndesmotic fixation to determine if there is loss or maintenance of correction. In addition, the effect of the type of rotational injury, early weight bearing, and the number of trans-syndesmotic screws used on the integrity of the inferior tibiofibular articulation or ankle mortise after screw removal were evaluated. An analysis was conducted of 86 patients, with an unstable rotational ankle fracture requiring open reduction with syndesmosis screw stabilization. Routine radiographic parameters were measured just after open reduction and just before syndesmotic screw removal. There was a high correlation of loss of the integrity of the syndesmotic parameters after screw removal. However, the medial clear space of the ankle changed an insignificant amount, suggesting that although there appears to be some loss of maintenance, the talus did not shift laterally at the expense of a mobile syndesmosis. Ankle injuries requiring stabilization of syndesmotic instability with use of temporary trans-syndesmotic fixation achieve a stable ankle mortise after removal. Tibiofibular diastasis is commonplace upon removal of the syndesmotic hardware, but the ankle mortise remains unchanged. Based on the radiographic criteria described in this study, the postoperative change in medial clear space or tibiofibular diastasis has no bearing on fracture type, deltoid injury, or the use of 1 or 2 cortical screws. As such, other unknown mechanisms affecting the integrity of the syndesmosis after screw removal are in place. (C) 2011 by the American College of Foot and Ankle Surgeons. All rights reserved. C1 [Schuberth, John M.] Kaiser Fdn Hosp, Dept Orthoped Surg, San Francisco, CA 94118 USA. [Jordan, Thomas H.] Kaiser Permanente Med Grp, Santa Rosa, CA USA. [Talarico, Ross H.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Schuberth, JM (reprint author), Kaiser Fdn Hosp, Dept Orthoped Surg, 450 6th Ave, San Francisco, CA 94118 USA. EM Jmfoot@aol.com NR 35 TC 15 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-2516 J9 J FOOT ANKLE SURG JI J. Foot Ankle Surg. PD JUL-AUG PY 2011 VL 50 IS 4 BP 407 EP 412 DI 10.1053/j.jfas.2011.03.014 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 782TY UT WOS:000292036100009 PM 21596590 ER PT J AU Larauche, M Mulak, A Tache, Y AF Larauche, Muriel Mulak, Agata Tache, Yvette TI Stress-Related Alterations of Visceral Sensation: Animal Models for Irritable Bowel Syndrome Study SO JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Review DE Irritable bowel syndrome; Models, animal; Pain AB Stressors of different psychological, physical or immune origin play a critical role in the pathophysiology of irritable bowel syndrome participating in symptoms onset, clinical presentation as well as treatment outcome. Experimental stress models applying a variety of acute and chronic exteroceptive or interoceptive stressors have been developed to target different periods throughout the lifespan of animals to assess the vulnerability, the trigger and perpetuating factors determining stress influence on visceral sensitivity and interactions within the brain-gut axis. Recent evidence points towards adequate construct and face validity of experimental models developed with respect to animals' age, sex, strain differences and specific methodological aspects such as non-invasive monitoring of visceromotor response to colorectal distension as being essential in successful identification and evaluation of novel therapeutic targets aimed at reducing stress-related alterations in visceral sensitivity. Underlying mechanisms of stress-induced modulation of visceral pain involve a combination of peripheral, spinal and supraspinal sensitization based on the nature of the stressors and dysregulation of descending pathways that modulate nociceptive transmission or stress-related analgesic response. C1 Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Digest Dis Div,Dept Med, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Larauche, M (reprint author), West Los Angeles VA Med Ctr, CURE Digest Dis Res Ctr, 11301 Wilshire Blvd,Bldg 115 Rm 111, Los Angeles, CA 90073 USA. EM mlarauche@mednet.ucla.edu OI Larauche, Muriel/0000-0003-3320-3675 FU VA Research Career Scientist Award; NIH [R01 DK-57238, DK 33061, P50 DK-64539, K01 DK088937] FX This review is part of studies supported by the VA Research Career Scientist Award, NIH grants R01 DK-57238 and DK 33061 and P50 DK-64539 (YT) and K01 DK088937 (ML). NR 310 TC 28 Z9 34 U1 2 U2 9 PU KOREAN SOC NEUROGASTERONTEROL & MOTILITY PI GANGNAM-GU PA RM 305, LOTTE GOLD ROSE VILL II, 31 SEOLLEUNG-RO 86-GIL, GANGNAM-GU, SEOUL 135-839, SOUTH KOREA SN 2093-0879 J9 J NEUROGASTROENTEROL JI J. Neurogastroenterol. Motil. PD JUL PY 2011 VL 17 IS 3 BP 213 EP 234 DI 10.5056/jnm.2011.17.3.213 PG 22 WC Gastroenterology & Hepatology; Clinical Neurology SC Gastroenterology & Hepatology; Neurosciences & Neurology GA V29WV UT WOS:000208779400003 PM 21860814 ER PT J AU Seo, Y Aparici, CM Chen, CP Hsu, C Kased, N Schreck, C Costouros, N Hawkins, R Shinohara, K Roach, M AF Seo, Youngho Aparici, Carina Mari Chen, Chien Peter Hsu, Charles Kased, Norbert Schreck, Carole Costouros, Nick Hawkins, Randall Shinohara, Katsuto Roach, Mack, III TI Mapping of Lymphatic Drainage from the Prostate Using Filtered Tc-99m-Sulfur Nanocolloid and SPECT/CT SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE prostate cancer; sulfur colloid; SPECT/CT; lymphatic mapping; sentinel node ID RADIATION-THERAPY; NODE DISSECTION; WHOLE-PELVIS; GAMMA-PROBE; CANCER; RADIOTHERAPY; LYMPHOSCINTIGRAPHY; INJECTION; INVASION AB We have developed a practice procedure for prostate lymphoscintigraphy using SPECT/CT and filtered Tc-99m-sulfur nanocolloid, as an alternative to the proprietary product Tc-99m-Nanocoll, which is not approved in the United States. Methods: Ten patients were enrolled for this study, and all received radiotracer prepared using a 100-nm membrane filter at a commercial radiopharmacy. Whole-body scans and SPECT/CT studies were performed within 1.5-3 h after the radiotracer had been administered directly into 6 locations of the prostate gland under transrectal ultrasound guidance. The radiation dose was estimated from the first 3 patients. Lymphatic drainage mapping was performed, and lymph nodes were identified. Results: The estimated radiation dose ranged from 3.9 to 5.2 mSv/MBq. The locations of lymph nodes draining the prostate gland were similar to those found using the proprietary product. Conclusion: When the proprietary radiolabeled nanocolloid indicated for lymphoscintigraphy is not available, prostate lymph node mapping and identification are still feasible using filtered Tc-99m-sulfur nanocolloid. C1 [Seo, Youngho; Aparici, Carina Mari; Schreck, Carole; Costouros, Nick; Hawkins, Randall] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94107 USA. [Seo, Youngho; Chen, Chien Peter; Hsu, Charles; Kased, Norbert; Shinohara, Katsuto; Roach, Mack, III] Univ Calif San Francisco, Helen Diller Family Comprehens Ctr, Dept Radiat Oncol, San Francisco, CA 94107 USA. [Seo, Youngho; Hawkins, Randall] Univ Calif San Francisco, Joint Grad Grp Bioengn, San Francisco, CA 94107 USA. [Aparici, Carina Mari] San Francisco VA Med Ctr, San Francisco, CA USA. [Shinohara, Katsuto; Roach, Mack, III] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94107 USA. RP Seo, Y (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 185 Berry St,Ste 350, San Francisco, CA 94107 USA. EM youngho.seo@ucsf.edu FU National Cancer Institute [K25 CA114254] FX We thank Marilyn Robinson at the University of California, San Francisco, for her help with coordinating the clinical study. We also thank Chang-Lae Lee, who helped with radiation dose calculations using biokinetic data. This study was partially funded by National Cancer Institute grant K25 CA114254. No other potential conflict of interest relevant to this article was reported. NR 20 TC 7 Z9 7 U1 0 U2 1 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 JUL 1 PY 2011 VL 52 IS 7 BP 1068 EP 1072 DI 10.2967/jnumed.110.085944 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 786IL UT WOS:000292297900011 PM 21680690 ER PT J AU Salinthone, S Schillace, RV Tsang, C Regan, JW Bourdette, DN Carr, DW AF Salinthone, Sonemany Schillace, Robynn V. Tsang, Catherine Regan, John W. Bourdette, Dennis N. Carr, Daniel W. TI Lipoic acid stimulates cAMP production via G protein-coupled receptor-dependent and -independent mechanisms SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE G protein-coupled receptors; Adenylyl cyclase; cAMP; Lipoic acid ID SOLUBLE ADENYLYL-CYCLASE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; T-CELL MIGRATION; ADENOSINE-MEDIATED INHIBITION; PROSTANOID RECEPTORS; CYTOKINE PRODUCTION; THIOCTIC ACID; NK CELLS; SIGNAL-TRANSDUCTION; MULTIPLE-SCLEROSIS AB Lipoic acid (LA) is a naturally occurring fatty acid that exhibits anti-oxidant and anti-inflammatory properties and is being pursued as a therapeutic for many diseases including multiple sclerosis, diabetic polyneuropathy and Alzheimer's disease. We previously reported on the novel finding that racemic LA (50:50 mixture of R-LA and S-LA) stimulates CAMP production, activates prostanoid EP2 and EP4 receptors and adenylyl cyclases (AC), and suppresses activation and cytotoxicity in NK cells. In this study, we present evidence that furthers our understanding of the mechanisms of action of LA. Using various LA derivatives, such as dihydrolipoic acid (DHLA),S,S-dimethyl lipoic acid (DMLA) and lipoamide (LPM), we discovered that only LA is capable of stimulating CAMP production in NK cells. Furthermore, there is no difference in cAMP production after stimulation with either R-LA, S-LA or racemic LA. Competition and synergistic studies indicate that LA may also activate AC independent of the EP2 and EP4 receptors. Pretreatment of PBMCs with KH7 (a specific peptide inhibitor of soluble AC) and the calcium inhibitor (Bapta) prior to LA treatment resulted in reduced cAMP levels, suggesting that soluble AC and calcium signaling mediate LA stimulation of cAMP production. In addition, pharmacological inhibitor studies demonstrate that LA also activates other G protein-coupled receptors, including histamine and adenosine but not the beta-adrenergic receptors. These novel findings provide information to better understand the mechanisms of action of LA, which can help facilitate the use of LA as a therapeutic for various diseases. (C) Published by Elsevier Inc. C1 [Salinthone, Sonemany; Schillace, Robynn V.; Tsang, Catherine; Bourdette, Dennis N.; Carr, Daniel W.] Portland VA Med Ctr, Portland, OR 97239 USA. [Salinthone, Sonemany; Schillace, Robynn V.; Bourdette, Dennis N.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Regan, John W.] Univ Arizona, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA. [Carr, Daniel W.] Oregon Hlth & Sci Univ, Dept Endocrinol, Portland, OR 97239 USA. RP Carr, DW (reprint author), Portland VA Med Ctr, Portland, OR 97239 USA. EM carrd@ohsu.edu FU Department of Veterans Affairs Biomedical Laboratory Research & Development Service; NIH [P50AT00066-01]; The National MS Society [CRG CA1055-A-3]; Laura Fund for Innovation in Multiple Sclerosis Research; Nancy Davis Center Without Walls; Collins Medical Trust FX This research was supported by the Department of Veterans Affairs Biomedical Laboratory Research & Development Service (D.W.C. and D.N.B.), NIH Grant P50AT00066-01 (D.N.B.), The National MS Society CRG CA1055-A-3 (D.N.B.), the Laura Fund for Innovation in Multiple Sclerosis Research (D.N.B.), the Nancy Davis Center Without Walls (D.N.B.), and the Collins Medical Trust (S.S.). NR 69 TC 17 Z9 17 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 EI 1873-4847 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD JUL PY 2011 VL 22 IS 7 BP 681 EP 690 DI 10.1016/j.jnutbio.2010.05.008 PG 10 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 787CR UT WOS:000292354700010 PM 21036588 ER PT J AU Bekelman, DB Nowels, CT Allen, LA Shakar, S Kutner, JS Matlock, DD AF Bekelman, David B. Nowels, Carolyn T. Allen, Larry A. Shakar, Simon Kutner, Jean S. Matlock, Daniel D. TI Outpatient Palliative Care for Chronic Heart Failure: A Case Series SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID SYMPTOM ASSESSMENT SCALE; QUALITY-OF-LIFE; DEPRESSION; MANAGEMENT; SURVIVAL; CANCER; PREVALENCE; DISEASE; END; HOSPITALIZATION AB Background/Objectives: Although the palliative care needs of outpatients with chronic heart failure (HF) are numerous, there is limited published experience in providing outpatient HF palliative care. This article describes the patients seen and the issues addressed in an outpatient palliative care program for patients with HF. Methods: Case series involving a retrospective medical record review using descriptive quantitative and qualitative analysis. Results: Over a 3 1/2 year time period, 50 patients were seen, resulting in 228 total visits. Fifty percent of patients were seen only once. Fifty-eight percent of patients had New York Heart Association (NYHA) Class III-IV HF. Within a year of the initial palliative care visit, 14% of patients died. Depression, anxiety, pain, fatigue, breathlessness, and sleep disturbance were common symptoms addressed during visits. Advance care planning topics were discussed with 48% of patients; hospice and resuscitation status were each discussed with 16% of patients. Fears or concerns about the future arose in 34% of patients. Care coordination was commonly addressed with patients' other health care providers (58%). The most common referrals were to social work (26%) and rehabilitation/physical therapy (20%). Conclusions: Several findings reflect how outpatient HF palliative care differs from that of inpatient hospital-based palliative care. Many of the issues addressed, including care coordination, advance care planning, and psychosocial issues, imply that palliative HF care is complementary to standard HF care at all stages of the disease process and that future programs should consider dedicating a nurse and/or social worker. Research is needed to test how such a care model affects patient-centered outcomes, utilization, and cost. C1 [Bekelman, David B.] Dept Vet Affairs Med Ctr, Denver, CO USA. [Bekelman, David B.; Nowels, Carolyn T.; Allen, Larry A.; Shakar, Simon; Kutner, Jean S.; Matlock, Daniel D.] Univ Colorado, Denver Sch Med, Aurora, CO USA. [Bekelman, David B.; Allen, Larry A.; Matlock, Daniel D.] Colorado Cardiovasc Outcomes Res, Denver, CO USA. [Allen, Larry A.; Shakar, Simon; Kutner, Jean S.; Matlock, Daniel D.] Univ Colorado Hosp, Aurora, CO USA. RP Bekelman, DB (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM david.bekelman@va.gov FU University of Colorado; Department of Veterans Affairs (HSRD) [CDA 08-022]; University of Colorado Hartford/Jahnigen Center for Excellence in Geriatric Medicine; Division of General Internal Medicine FX This research was funded by the University of Colorado Program in Palliative Care Research Fund. Dr. Bekelman is funded through the Department of Veterans Affairs (HSR&D CDA 08-022) and was also funded by University of Colorado Hartford/Jahnigen Center for Excellence in Geriatric Medicine and the Division of General Internal Medicine while running the Supportive Care Program. The funding organizations had no role in any part of the study. The views in this article are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs. NR 48 TC 17 Z9 17 U1 2 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JUL PY 2011 VL 14 IS 7 BP 815 EP 821 DI 10.1089/jpm.2010.0508 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 782PP UT WOS:000292021900007 PM 21554021 ER PT J AU Kim, B Viel, KR Marder, VJ Howard, TE AF Kim, B. Viel, K. R. Marder, V. J. Howard, T. E. TI ADAMTS13 single-nucleotide polymorphisms in geographically-diverse populations SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Kim, B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90024 USA. [Viel, K. R.; Marder, V. J.] St Josephs Hosp, St Josephs Translat Res Inst, Phoenix, AZ USA. [Howard, T. E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI MA P-TU-473 BP 456 EP 456 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA V33AX UT WOS:000208992801255 ER PT J AU Lewis, KB Nguyen, PCT Norby-Slycord, C Howard, TE Key, NS Pratt, KP AF Lewis, K. B. Nguyen, P-C T. Norby-Slycord, C. Howard, T. E. Key, N. S. Pratt, K. P. TI Phenotypes of allo- and auto-immune antibody responses to FVIII characterized by surface plasmon resonance SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Lewis, K. B.; Nguyen, P-C T.; Norby-Slycord, C.; Pratt, K. P.] Puget Sound Blood Ctr, Res Dept, Seattle, WA USA. [Howard, T. E.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Key, N. S.] Univ N Carolina, Hemophilia & Thrombosis Ctr, Chapel Hill, NC 27515 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI MA P-WE-184 BP 578 EP 578 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA V33AX UT WOS:000208992802092 ER PT J AU Pinne, M Haake, D AF Pinne, Marija Haake, David TI Immuno-fluorescence Assay of Leptospiral Surface-exposed Proteins SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article C1 [Pinne, Marija] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Pinne, Marija] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Haake, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Haake, David] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Gent, Los Angeles, CA 90095 USA. [Haake, David] Vet Affairs Greater Angeles Hlth Care Syst, Div Infect Dis, Los Angeles, CA USA. RP Pinne, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. EM mpinne@ucla.edu NR 17 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JUL PY 2011 IS 53 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36MC UT WOS:000209215000019 ER PT J AU Bickel, CS Cross, JM Bamman, MM AF Bickel, C. Scott Cross, James M. Bamman, Marcas M. TI Exercise Dosing to Retain Resistance Training Adaptations in Young and Older Adults SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE MUSCLE FIBER; SARCOPENIA; EXERCISE DOSE; HYPERTROPHY; AGING; ATROPHY ID SKELETAL-MUSCLE ADAPTATIONS; MYOFIBER HYPERTROPHY; GENE-EXPRESSION; STRENGTH; MEN; WOMEN; FORCE; AGE; INTENSITY; PEOPLE AB BICKEL, C. S., J. M. CROSS, and M. M. BAMMAN. Exercise Dosing to Retain Resistance Training Adaptations in Young and Older Adults. Med. Sci. Sports Exerc., Vol. 43, No. 7, pp. 1177-1187, 2011. Resistance training (RT) is a proven sarcopenia countermeasure with a high degree of potency. However, sustainability remains a major issue that could limit the appeal of RT as a therapeutic approach without well-defined dosing requirements to maintain gains. Purpose: To test the efficacy of two maintenance prescriptions on muscle mass, myofiber size and type distribution, and strength. We hypothesized the minimum dose required to maintain RT-induced adaptations would be greater in the old (60-75 yr) versus young (20-35 yr). Methods: Seventy adults participated in a two-phase exercise trial that consisted of RT 3 d.wk(-1) for 16 wk (phase 1) followed by a 32-wk period (phase 2) with random assignment to detraining or one of two maintenance prescriptions (reducing the dose to one-third or one-ninth of that during phase 1). Results: Phase 1 resulted in expected gains in strength, myofiber size, and muscle mass along with the typical IIx-to-IIa shift in myofiber-type distribution. Both maintenance prescriptions preserved phase 1 muscle hypertrophy in the young but not the old. In fact, the one-third maintenance dose led to additional myofiber hypertrophy in the young. In both age groups, detraining reversed the phase 1 IIx-to-IIa myofiber-type shift, whereas a dose response was evident during maintenance training with the one-third dose better maintaining the shift. Strength gained during phase 1 was largely retained throughout detraining with only a slight reduction at the final time point. Conclusions: We conclude that older adults require a higher dose of weekly loading than the young to maintain myofiber hypertrophy attained during a progressive RT program, yet gains in specific strength among older adults were well preserved and remained at or above levels of the untrained young. C1 [Bickel, C. Scott] Univ Alabama, Dept Physiol & Biophys, Core Muscle Res Lab, Birmingham, AL 35294 USA. [Bickel, C. Scott] Univ Alabama, Dept Phys Therapy, Birmingham, AL 35294 USA. [Cross, James M.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. [Bamman, Marcas M.] Birmingham Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Birmingham, AL USA. [Bickel, C. Scott; Bamman, Marcas M.] UAB Ctr Exercise Med, Birmingham, AL USA. RP Bamman, MM (reprint author), Univ Alabama, Dept Physiol & Biophys, Core Muscle Res Lab, MCLM 966,1530 3rd Ave S, Birmingham, AL 35294 USA. EM mbamman@uab.edu FU National Institute on Aging [1R01 AG017896, 1R01 AG027084-S1]; VA Merit Review grant FX This work was sponsored by National Institute on Aging grants 1R01 AG017896 (MMB) and 1R01 AG027084-S1 (CSB), and a VA Merit Review grant (MMB). NR 42 TC 25 Z9 25 U1 5 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUL PY 2011 VL 43 IS 7 BP 1177 EP 1187 DI 10.1249/MSS.0b013e318207c15d PG 11 WC Sport Sciences SC Sport Sciences GA 781IQ UT WOS:000291924500007 PM 21131862 ER PT J AU Fletcher, CE Copeland, LA Lowery, JC Reeves, PJ AF Fletcher, Carol E. Copeland, Laurel A. Lowery, Julie C. Reeves, Pamela J. TI Nurse Practitioners as Primary Care Providers Within the VA SO MILITARY MEDICINE LA English DT Article ID INSTITUTIONAL REORGANIZATION; COMORBIDITY INDEX; AMBULATORY CARE; PILOT PROGRAM; PHYSICIANS; OUTCOMES; VETERANS; QUALITY; DISEASE; TRIAL AB We examined the perceptions of nurse practitioners (NPs) and physicians regarding NPs' roles as primary care providers within the Department of Veterans Affairs, thus suggesting possible reasons for the variation of NPs use. NPs and physicians from 7 Veterans Affairs hospitals were surveyed regarding perceptions and concerns about NPs' responsibilities. Quality of care was verified through outpatient services, laboratory results, and medications prescribed for 104,226 hypertensive or diabetic patients. Clinical findings suggest primary care for diabetic and hypertensive patients was comparable. Survey findings suggest physicians tended to underestimate what NPs do on their own for acute patients. Both groups expressed some concerns about expectations for NPs. To successfully integrate NPs into the primary care environment, health systems need to pay increased attention to differences in role perceptions among primary care providers. C1 [Fletcher, Carol E.; Lowery, Julie C.] VA Ann Arbor Med Ctr, Ann Arbor, MI 48108 USA. [Copeland, Laurel A.] S Texas Vet Healthcare Syst, San Antonio, TX 78229 USA. [Reeves, Pamela J.] John D Dingell Vet Med Ctr, Detroit, MI 48201 USA. RP Fletcher, CE (reprint author), VA Ann Arbor Med Ctr, 2215 Fuller Rd 127, Ann Arbor, MI 48108 USA. OI Copeland, Laurel/0000-0002-9478-0209 FU VISN 11 in Ann Arbor, Michigan; Veterans Evidence-based Research Dissemination; South Texas Veterans Health Care System, San Antonio, Texas; Health Services Research and Development Service of the Department of VA; VA Health Services [MRP-05-145] FX This article is based on the work supported by VISN 11 in Ann Arbor, Michigan, Veterans Evidence-based Research Dissemination and Implementation Cen-Ter (VERDICT) research program at the South Texas Veterans Health Care System, San Antonio, Texas, and the Health Services Research and Development Service of the Department of VA. Dr. Copeland was funded by VA Health Services Research and Development award MRP-05-145. NR 40 TC 4 Z9 4 U1 0 U2 15 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 JUL PY 2011 VL 176 IS 7 BP 791 EP 797 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 792XO UT WOS:000292783900010 PM 22128721 ER PT J AU Hoglinger, GU Melhem, NM Dickson, DW Sleiman, PMA Wang, LS Klei, L Rademakers, R de Silva, R Litvan, I Riley, DE van Swieten, JC Heutink, P Wszolek, ZK Uitti, RJ Vandrovcova, J Hurtig, HI Gross, RG Maetzler, W Goldwurm, S Tolosa, E Borroni, B Pastor, P Cantwell, LB Han, MR Dillman, A van der Brug, MP Gibbs, JR Cookson, MR Hernandez, DG Singleton, AB Farrer, MJ Yu, CE Golbe, LI Revesz, T Hardy, J Lees, AJ Devlin, B Hakonarson, H Muller, U Schellenberg, GD AF Hoeglinger, Guenter U. Melhem, Nadine M. Dickson, Dennis W. Sleiman, Patrick M. A. Wang, Li-San Klei, Lambertus Rademakers, Rosa de Silva, Rohan Litvan, Irene Riley, David E. van Swieten, John C. Heutink, Peter Wszolek, Zbigniew K. Uitti, Ryan J. Vandrovcova, Jana Hurtig, Howard I. Gross, Rachel G. Maetzler, Walter Goldwurm, Stefano Tolosa, Eduardo Borroni, Barbara Pastor, Pau Cantwell, Laura B. Han, Mi Ryung Dillman, Allissa van der Brug, Marcel P. Gibbs, J. Raphael Cookson, Mark R. Hernandez, Dena G. Singleton, Andrew B. Farrer, Matthew J. Yu, Chang-En Golbe, Lawrence I. Revesz, Tamas Hardy, John Lees, Andrew J. Devlin, Bernie Hakonarson, Hakon Mueller, Ulrich Schellenberg, Gerard D. CA PSP Genetics Study Grp TI Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; UNFOLDED PROTEIN RESPONSE; ALZHEIMERS-DISEASE; CORTICOBASAL DEGENERATION; NEUROPATHOLOGIC CRITERIA; PARKINSONS-DISEASE; TAU-GENE; HAPLOTYPE; EXPRESSION; METAANALYSIS AB Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP (cases) and 3,247 controls (stage 1) followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the stage 1 SNPs that yielded P <= 10(-3). We found significant previously unidentified signals (P < 5 x 10(-8)) associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. C1 [Wang, Li-San; Cantwell, Laura B.; Han, Mi Ryung; Schellenberg, Gerard D.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Hoeglinger, Guenter U.] Univ Marburg, Dept Neurol, Marburg, Germany. [Melhem, Nadine M.; Klei, Lambertus; Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Dickson, Dennis W.; Rademakers, Rosa] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Sleiman, Patrick M. A.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [de Silva, Rohan; Vandrovcova, Jana; Gibbs, J. Raphael; Hernandez, Dena G.; Hardy, John; Lees, Andrew J.] UCL, Inst Neurol, Reta Lila Weston Inst, London, England. [Litvan, Irene] Univ Louisville, Div Movement Disorders, Dept Neurol, Louisville, KY 40292 USA. [Riley, David E.] Case Western Reserve Univ, Dept Neurol, Univ Hosp, Cleveland, OH 44106 USA. [van Swieten, John C.] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands. [Heutink, Peter] Vrije Univ VU Med Ctr, Dept Clin Genet, Sect Med Genom, Amsterdam, Netherlands. [Wszolek, Zbigniew K.; Uitti, Ryan J.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Hurtig, Howard I.; Gross, Rachel G.] Univ Penn Hlth Syst, Dept Neurol, Philadelphia, PA USA. [Maetzler, Walter] Univ Tubingen, Dept Neurodegenerat, Hertie Inst Clin Brain Res, Ctr Neurol, Tubingen, Germany. [Maetzler, Walter] Univ Tubingen, German Ctr Neurodegenerat Dis, Tubingen, Germany. [Goldwurm, Stefano] Ist Clin Perfezionamento, Parkinson Inst, Milan, Italy. [Tolosa, Eduardo] Univ Barcelona, IDIBAPS, CIBERNED, Neurol Serv,Hosp Clin, Barcelona, Spain. [Borroni, Barbara] Univ Brescia, Inst Neurol, Dept Med & Surg Sci, Brescia, Italy. [Pastor, Pau] Inst Salud Carlos III, CIBERNED, Madrid, Spain. [Pastor, Pau] Univ Navarra, Ctr Appl Med Res, Div Neurosci, Neurogenet Lab, E-31080 Pamplona, Spain. [Pastor, Pau] Univ Navarra, Clin Univ Navarra, Dept Neurol, E-31080 Pamplona, Spain. [Dillman, Allissa; Gibbs, J. Raphael; Cookson, Mark R.; Hernandez, Dena G.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [van der Brug, Marcel P.] Scripps Res Inst, Dept Neurosci, Jupiter, FL USA. [Farrer, Matthew J.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Yu, Chang-En] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Yu, Chang-En] Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. [Golbe, Lawrence I.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08903 USA. [Revesz, Tamas; Lees, Andrew J.] UCL, UCL Inst Neurol, Dept Mol Neurosci, Queen Sq Brain Bank Neurol Disorders, London, England. [Mueller, Ulrich] Univ Giessen, Inst Humangenet, Giessen, Germany. RP Schellenberg, GD (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. EM ulrich.mueller@humangenetik.med.uni-giessen.de; gerardsc@mail.med.upenn.edu RI Silveira-Moriyama, Laura/G-4592-2014; Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Lees, Andrew/A-6605-2009; Ross, Owen/D-7573-2013; Melhem, Nadine/G-1510-2013; Troakes, Claire/K-4346-2015; Maetzler, Walter/A-6796-2011; Goldwurm, Stefano/Q-8978-2016; Morris, Huw/B-8527-2008; Pastor, Pau/C-9834-2009; Revesz, Tamas/A-8732-2010; O'Sullivan, Sean/C-9333-2012 OI Silveira-Moriyama, Laura/0000-0002-8267-0977; Budka, Herbert/0000-0002-1933-1577; van Swieten, John /0000-0001-6278-6844; Geller, Evan/0000-0002-8035-8736; CILIA, ROBERTO/0000-0002-1990-1939; Pickering-Brown, Stuart/0000-0003-1561-6054; Standaert, David/0000-0003-2921-8348; Litvan, Irene/0000-0002-3485-3445; Goldwurm, Stefano/0000-0002-1651-567X; Morris, Huw/0000-0002-5473-3774; Pastor, Pau/0000-0002-7493-8777; Revesz, Tamas/0000-0003-2501-0259; Rohrer, Jonathan/0000-0002-6155-8417; O'Sullivan, Sean/0000-0002-0583-7956; Dickson, Dennis W/0000-0001-7189-7917 FU CurePSP Foundation; Peebler PSP Research Foundation; US National Institutes of Health (NIH) (National Institute on Aging (NIA)/NIH) [R37 AG 11762, R01 PAS-03-092, P50 NS72187, P01 AG17216]; US National Institutes of Health (NIH) (National Institute of Mental Health (NIMH) [MH057881, MH077930]; NIA; German National Genome Research Network [01GS08136-4]; Deutsche Forschungsgemeinschaft [HO 2402/6-1]; Prinses Beatrix Fonds [01-0128]; Reta Lila Weston Trust; UK Medical Research Council [G0501560, G0400074]; Newcastle National Institute for Health Research (NIHR) Biomedical Research Centre in Ageing and Age Related Diseases; Alzheimer's Society; Alzheimer's Research Trust; TELETHON Italy [GTB07001]; Fondazione Grigioni per il Morbo di Parkinson; Wellcome Trust; Howard Hughes Medical Institute; Canadian Institute of Health Research; Federal Ministry of Education and Research (BMBF) [01GI0505]; PSP (Europe) Association; Cure PSP+; NIH/NINDS [1RC2NS070276, NS057567, P50NS072187]; Mayo Clinic Florida (MCF) Research Committee [90052030]; Government of Navarra; Division of Neuroscience, NIA; Division of Aging Biology and the Division of Geriatrics and Clinical Gerontology, NIA; National Human Genome Research Institute (NHGRI) [U01HG004608]; National Institute for General Medical Sciences (NIGMS); Marshfield Clinic, Health Resources Service Administration Office of Rural Health Policy [D1A RH00025]; Wisconsin Department of Commerce [TDF FYO10718]; NIH [U01HG004438] FX We thank the subjects and their families that participated in this study. This work was funded by grants from the CurePSP Foundation, the Peebler PSP Research Foundation and US National Institutes of Health (NIH) grants R37 AG 11762, R01 PAS-03-092, P50 NS72187, P01 AG17216 (National Institute on Aging (NIA)/NIH), MH057881 and MH077930 (National Institute of Mental Health (NIMH)). Work was also supported in part by the NIA Intramural Research Program, the German National Genome Research Network (01GS08136-4) and the Deutsche Forschungsgemeinschaft (HO 2402/6-1), Prinses Beatrix Fonds (JCvS, 01-0128), the Reta Lila Weston Trust and the UK Medical Research Council (RdS: G0501560). The Newcastle Brain Tissue Resource provided tissue and is funded in part by a grant from the UK Medical Research Council (G0400074), by the Newcastle National Institute for Health Research (NIHR) Biomedical Research Centre in Ageing and Age Related Diseases to the Newcastle upon Tyne Hospitals National Health Service Foundation Trust and by a grant from the Alzheimer's Society and Alzheimer's Research Trust as part of the Brains for Dementia Research Project. We acknowledge the contribution of many tissue samples from the Harvard Brain Tissue Resource Center. We also acknowledge the 'Human Genetic Bank of Patients affected by Parkinson Disease and Parkinsonism' (http://www.parkinson.it/dnabank.html) of the Telethon Genetic Biobank Network, supported by TELETHON Italy (project no. GTB07001) and by Fondazione Grigioni per il Morbo di Parkinson. The University of Toronto sample collection was supported by grants from Wellcome Trust, Howard Hughes Medical Institute and the Canadian Institute of Health Research. Brain-Net-Germany is supported by the Federal Ministry of Education and Research (BMBF) (01GI0505). R.d.S., A.J.L. and J.A.H. are funded by the Reta Lila Weston Trust and the PSP (Europe) Association. R.d.S. is funded by the UK Medical Research Council (Grant G0501560) and Cure PSP+. Z.K.W. is partially supported by the NIH/NINDS 1RC2NS070276, NS057567, P50NS072187, Mayo Clinic Florida (MCF) Research Committee CR programs (MCF #90052030 and MCF #90052030) and the gift from C. E. Bolch Jr. and S. B. Bolch (MCF #90052031/PAU # 90052). The Mayo Clinic College of Medicine would like to acknowledge M. Baker, R. Crook, M. DeJesus-Hernandez and N. Rutherford for their preparation of samples. P. P. was supported by a grant from the Government of Navarra ('Ayudas para la Realizacion de Proyectos de Investigacion' 2006-2007) and acknowledges the 'Iberian Atypical Parkinsonism Study Group Researchers': M. A. Pastor, M. R. Luquin, M. Riverol, J.A. Obeso and M. C. Rodriguez-Oroz (Department of Neurology, Clinica Universitaria de Navarra, University of Navarra, Pamplona, Spain), M. Blazquez (Neurology Department, Hospital Universitario Central de Asturias, Oviedo, Spain), A. Lopez de Munain, B. Indakoetxea, J. Olaskoaga, J. Ruiz, J. Felix Marti Masso (Servicio de Neurologia, Hospital Donostia, San Sebastian, Spain), V. Alvarez (Genetics Department, Hospital Universitario Central de Asturias, Oviedo, Spain), T. Tu on (Banco de Tejidos Neurologicos, CIBERNED, Hospital de Navarra, Navarra, Spain), F. Moreno (Servicio de Neurologia, Hospital Ntra. Sra. de la Antigua, Zumarraga, Gipuzkoa, Spain), A. Alzualde (Neurogenetics Department, Hospital Donostia, San Sebastian, Spain). E. T. wishes to acknowledge the Banco de Tejidos Neurologicos de la Universidad de Barcelona-Hospital Clinic, which provided many tissue samples for the project. We also acknowledge E.; Loomis for providng technical support.; The datasets used for older controls were obtained from Database for Genotypes and Phenotypes (dbGap) at http://www.ncbi.nlm.nih.gov/gap/. Funding support for the 'Genetic Consortium for Late Onset Alzheimer's Disease' was provided through the Division of Neuroscience, NIA. The Genetic Consortium for Late Onset Alzheimer's Disease (study accession number: phs000168.v1.p1) includes a genome-wide association study funded as part of the Division of Neuroscience, NIA. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by Genetic Consortium for Late Onset Alzheimer's Disease. Funding support for the 'CIDR Visceral Adiposity Study' (study accession number: phs000169.v1.p1) was provided through the Division of Aging Biology and the Division of Geriatrics and Clinical Gerontology, NIA. The CIDR Visceral Adiposity Study includes a genome-wide association study funded as part of the Division of Aging Biology and the Division of Geriatrics and Clinical Gerontology, NIA. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by Heath ABC Study Investigators. Funding support for the Personalized Medicine Research Project (PMRP) was provided through a cooperative agreement (U01HG004608) with the National Human Genome Research Institute (NHGRI), with additional funding from the National Institute for General Medical Sciences (NIGMS). The samples used for PMRP analyses were obtained with funding from Marshfield Clinic, Health Resources Service Administration Office of Rural Health Policy grant number D1A RH00025 and Wisconsin Department of Commerce Technology Development Fund contract number TDF FYO10718. Funding support for genotyping, which was performed at Johns Hopkins University, was provided by the NIH (U01HG004438). Assistance with phenotype harmonization and genotype cleaning was provided by the eMERGE Administrative Coordinating Center (U01HG004603) and the National Center for Biotechnology Information (NCBI). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000170.v1.p1. NR 46 TC 161 Z9 163 U1 2 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2011 VL 43 IS 7 BP 699 EP U125 DI 10.1038/ng.859 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 784UV UT WOS:000292184600017 PM 21685912 ER PT J AU Ingram, KH Lara-Castro, C Gower, BA Makowsky, R Allison, DB Newcomer, BR Munoz, AJ Beasley, TM Lawrence, JC Lopez-Ben, R Rigsby, DY Garvey, WT AF Ingram, Katherine H. Lara-Castro, Cristina Gower, Barbara A. Makowsky, Robert Allison, David B. Newcomer, Bradley R. Munoz, A. Julian Beasley, T. Mark Lawrence, Jeannine C. Lopez-Ben, Robert Rigsby, Dana Y. Garvey, W. Timothy TI Intramyocellular Lipid and Insulin Resistance: Differential Relationships in European and African Americans SO OBESITY LA English DT Article ID TYPE-2 DIABETIC SUBJECTS; VISCERAL ADIPOSE-TISSUE; METABOLIC SYNDROME; SKELETAL-MUSCLE; WEIGHT-LOSS; ETHNIC-DIFFERENCES; ABDOMINAL FAT; WHITE WOMEN; SENSITIVITY; OBESITY AB Insulin resistance has been associated with the accumulation of fat within skeletal muscle fibers as intramyocellular lipid (IMCL). Here, we have examined in a cross-sectional study the interrelationships among IMCL, insulin sensitivity, and adiposity in European Americans (EAs) and African Americans (AAs). In 43 EA and 43 AA subjects, we measured soleus IMCL content with proton-magnetic resonance spectroscopy, insulin sensitivity with hyperinsulinemic-euglycemic clamp, and body composition with dual-energy X-ray absorptiometry. The AA and EA subgroups had similar IMCL content, insulin sensitivity, and percent fat, but only in EA was IMCL correlated with insulin sensitivity (r = -0.47, P < 0.01), BMI (r = 0.56, P < 0.01), percent fat (r = 0.35, P < 0.05), trunk fat (r = 0.47, P < 0.01), leg fat (r = 0.40, P < 0.05), and waist and hip circumferences (r = 0.54 and 0.55, respectively, P < 0.01). In a multiple regression model including IMCL, race, and a race by IMCL interaction, the interaction was found to be a significant predictor (t = 1.69, DF = 1, P = 0.0422). IMCL is related to insulin sensitivity and adiposity in EA but not in AA, suggesting that IMCL may not function as a pathophysiological factor in individuals of African descent. These results highlight ethnic differences in the determinants of insulin sensitivity and in the pathogenesis of the metabolic syndrome trait cluster. C1 [Ingram, Katherine H.; Makowsky, Robert; Allison, David B.; Beasley, T. Mark] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. [Lara-Castro, Cristina; Gower, Barbara A.; Munoz, A. Julian; Lawrence, Jeannine C.; Rigsby, Dana Y.; Garvey, W. Timothy] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. [Lara-Castro, Cristina; Munoz, A. Julian] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Newcomer, Bradley R.] Univ Alabama, Dept Clin & Diagnost Sci, Birmingham, AL USA. [Lopez-Ben, Robert] Univ Alabama, Dept Radiol, Birmingham, AL USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Ingram, KH (reprint author), Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. EM khingram@uab.edu OI Allison, David/0000-0003-3566-9399 FU National Institutes of Health [DK-038765, DK-083562, PO1 HL-55782]; T32 training grant [HL-007457, HL-072757]; Department of Veterans Affairs; UAB Center for Clinical and Translational Science [UL1 RR025777]; Diabetes Research and Training Center [P60 DK079626] FX We thank the research volunteers for their participation in this study. This work was supported from grants from the National Institutes of Health (DK-038765, DK-083562, PO1 HL-55782), the T32 training grant (HL-007457) entitled "Mechanisms of Hypertension and Cardiovascular Diseases" (PI: S. Oparil), the T32 training grant (HL-072757) entitled "UAB Statistical Genetics Post-Doctoral Training Program" (PI: D. B. A.), and by the Merit Review program of the Department of Veterans Affairs. We also acknowledge support from the UAB Center for Clinical and Translational Science (UL1 RR025777), and core facility support from the Clinical Nutrition Research Unit (P30-DK56336), and the Diabetes Research and Training Center (P60 DK079626). We further acknowledge Dr. Jan den Hollander at UAB for his assistance with IMCL measurements. NR 40 TC 24 Z9 24 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD JUL PY 2011 VL 19 IS 7 BP 1469 EP 1475 DI 10.1038/oby.2011.45 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 784CU UT WOS:000292132300022 PM 21436797 ER PT J AU Livhits, M Mercado, C Yermilov, I Parikh, JA Dutson, E Mehran, A Ko, CY Gibbons, MM AF Livhits, Masha Mercado, Cheryl Yermilov, Irina Parikh, Janak A. Dutson, Erik Mehran, Amir Ko, Clifford Y. Gibbons, Melinda Maggard TI Patient behaviors associated with weight regain after laparoscopic gastric bypass SO OBESITY RESEARCH & CLINICAL PRACTICE LA English DT Article DE Bariatric surgery; Weight regain; Behavioral factors ID TERM-FOLLOW-UP; BARIATRIC SURGERY; PSYCHIATRIC-DISORDERS; MORBID-OBESITY; IMPACT; PARTICIPATION; QUESTIONNAIRE; PREDICTORS; ATTENDANCE; OUTCOMES AB Background: Patients undergoing gastric bypass lose substantial weight, but 20% regain weight starting at 2 years after surgery. Our objective was to identify behavioral predictors of weight regain after laparoscopic Roux-en-Y gastric bypass (LRYGB). Methods: We retrospectively surveyed 197 patients for factors predictive of weight regain (>= 15% from lowest weight to weight at survey completion). Consecutive patients who had bariatric surgery from 1/2003 through 12/2008 were identified from an existing database. Response rate was 76%, with 150 patients completing the survey. Results: Follow-up after LRYGB was 45.0+/-12.7 months, 22% of patients had weight regain. After controlling for age, gender, and follow-up time, factors associated with weight regain included low physical activity (odds ratio (OR) 6.92, P=0.010), low self-esteem (OR 6.86, P=0.008), and Eating Inventory Disinhibition (OR 1.30, P=0.029). Conclusions: Physical activity, self-esteem, and maladaptive eating may be associated with weight regain after LRYGB. These factors should be addressed in prospective studies of weight loss following bariatric surgery, as they may identify patients at risk for weight regain who may benefit from tailored interventions. C1 [Livhits, Masha; Mercado, Cheryl; Yermilov, Irina; Parikh, Janak A.; Dutson, Erik; Mehran, Amir; Ko, Clifford Y.; Gibbons, Melinda Maggard] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Livhits, Masha; Yermilov, Irina; Parikh, Janak A.; Ko, Clifford Y.; Gibbons, Melinda Maggard] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA 90073 USA. [Gibbons, Melinda Maggard] Olive View UCLA, Dept Surg, Sylmar, CA 91342 USA. RP Livhits, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 LeConte Ave,72-215 CHS, Los Angeles, CA 90095 USA. EM mlivhits@mednet.ucla.edu FU VA Department of Surgery, Robert Wood Johnson Physician Faculty Scholars Program FX VA Department of Surgery, Robert Wood Johnson Physician Faculty Scholars Program. NR 33 TC 2 Z9 2 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1871-403X J9 OBES RES CLIN PRACT JI Obes. Res. Clin. Pract. PD JUL-SEP PY 2011 VL 5 IS 3 BP E258 EP E265 DI 10.1016/j.orcp.2011.03.004 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 981GU UT WOS:000306955800010 ER PT J AU Evans, CT Rogers, TJ Burns, SP Lopansri, B Weaver, FM AF Evans, Charlesnika T. Rogers, Thea J. Burns, Stephen P. Lopansri, Bert Weaver, Frances M. TI Knowledge and Use of Antimicrobial Stewardship Resources by Spinal Cord Injury Providers SO PM&R LA English DT Article ID BLOOD-STREAM INFECTIONS; HEALTH-CARE EPIDEMIOLOGY; INSTITUTIONAL PROGRAM; REHABILITATION UNIT; AMERICA GUIDELINES; DISEASES SOCIETY; RESISTANCE; MORTALITY; PHYSICIAN; VETERANS AB Objective: To assess the knowledge and the use of antimicrobial stewardship resources, such as hospital antibiograms and infectious disease consultants, by spinal cord injury or disorder (SCI/D) providers. Design and Setting: Anonymous Internet-based, cross-sectional survey. Participants: A total of 314 SCI/D physicians, nurse practitioners, and physician assistants who prescribe antibiotics were invited to complete a survey. Main Outcome Measurements: Knowledge of and behaviors related to antibiograms and infectious disease (ID) consults. Results: A total of 118 providers (80 physicians, 20 nurse practitioners, 18 physician assistants) completed the survey (37.6% response rate). Approximately one-third of respondents indicated that they did not have access to (11.0%) or were unsure of (28.0%) the existence of facility antibiograms. Half of the providers indicated that they never used antibiograms to determine treatment for their SCI/D patients. Respondent factors associated with viewing facility antibiograms were older age, employment at SCI/D specialty centers, a longer duration since completion of training, and years of SCI/D patient care. Nearly all respondents (95%) indicated that they believed that improving access to antibiotic prescribing data or antibiograms would reduce antibiotic resistance. More than one-third reported that they never or seldom used ID consults. Conclusions: A significant portion of SCI/D providers who prescribe antibiotics do not have access to facility antibiograms or are unaware of their existence and thus could not use them for determining antibiotic treatment. Interventions could include formal education of providers on how to access antibiograms and the use of ID physicians as a resource, as well as providing technologic support, such as electronic facility-level antibiograms as part of the medical record system, which can be easily identified if a provider is making a decision on an antibiotic. PM R 2011;3:619-623 C1 [Evans, Charlesnika T.] Edward J Hines Jr VA Hosp 151H, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Evans, Charlesnika T.] Edward J Hines Jr VA Hosp 151H, Spinal Cord Injury Qual Enhancement Res Initiat, Dept Vet Affairs VA, Hines, IL 60141 USA. [Evans, Charlesnika T.] Northwestern Univ, Inst Healthcare Studies, Feinberg Sch Med, Chicago, IL 60611 USA. [Rogers, Thea J.; Weaver, Frances M.] Edward Hines Jr VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA. [Rogers, Thea J.; Weaver, Frances M.] Edward Hines Jr VA Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Dept Vet Affairs VA, Hines, IL USA. [Burns, Stephen P.] VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA USA. [Burns, Stephen P.] Univ Washington, Seattle, WA 98195 USA. [Lopansri, Bert; Weaver, Frances M.] Loyola Univ Hlth Syst, Dept Med, Maywood, IL USA. [Lopansri, Bert] Edward Hines Jr VA Hosp, Dept Vet Affairs VA, Infect Dis Serv, Hines, IL USA. RP Evans, CT (reprint author), Edward J Hines Jr VA Hosp 151H, Ctr Management Complex Chron Care, 5th Ave & Roosevelt Rd,POB 5000,Rm D302, Hines, IL 60141 USA. EM Charlesnika.Evans@va.gov FU Department of Veterans Affairs; Office of Research and Development; Health Services Research and Development Service; SCI QUERI [98-000]; Paralyzed Veterans of America Research Foundation [2562] FX Supported by the Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service, SCI QUERI (98-000) and the Paralyzed Veterans of America Research Foundation (Project 2562). NR 27 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD JUL PY 2011 VL 3 IS 7 BP 619 EP 623 DI 10.1016/j.pmrj.2011.03.021 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 961BC UT WOS:000305437900004 PM 21777860 ER PT J AU Basile, J AF Basile, Jan TI A New Approach to Glucose Control in Type 2 Diabetes: The Role of Kidney Sodium-Glucose Co-transporter 2 Inhibition SO POSTGRADUATE MEDICINE LA English DT Article DE diabetes; hyperglycemia; glucose reabsorption; SGLT2; pharmacotherapy; oral antidiabetics ID TRANSPORTER GENE-EXPRESSION; INADEQUATE GLYCEMIC CONTROL; SELECTIVE SGLT2 INHIBITOR; MICROVASCULAR COMPLICATIONS; THERAPEUTIC TARGET; RENAL GLUCOSURIA; HEALTHY-SUBJECTS; BLOOD-GLUCOSE; DOUBLE-BLIND; URIC-ACID AB Hyperglycemia is a defining characteristic of type 2 diabetes mellitus and is a major risk factor associated with the development of many microvascular complications. There are numerous therapies currently available to treat hyperglycemia, but glycemic control rates remain poor. One potential reason is the decline in beta-cell function over time, which decreases the effectiveness of therapies that rely on insulin action. The kidney occupies a central position in the control of glucose homeostasis by its role in gluconeogenesis and by regulating glucose excretion. Under normal conditions, glucose filtered by the kidney is virtually totally reabsorbed in the proximal tubule by the sodium-glucose co-transporter 2 (SGLT2). Inhibition of SGLT2 is an attractive, insulin-independent target for increasing glucose excretion in the setting of hyperglycemia. A number of SGLT2 inhibitors have been synthesized, and results from preclinical studies have shown that they increase glucose excretion and normalize plasma glucose in diabetic models. Initial clinical data are promising and suggest that SGLT2 inhibitors may be a new therapeutic option for treating type 2 diabetes mellitus. C1 Med Univ S Carolina, Div Gen Internal Med, Seinsheimer Cardiovasc Hlth Program, Ralph H Johnson VA Med Ctr, Charleston, SC 29403 USA. RP Basile, J (reprint author), Med Univ S Carolina, Div Gen Internal Med, Seinsheimer Cardiovasc Hlth Program, Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29403 USA. EM basilejn@musc.edu FU Bristol-Myers Squibb; AstraZeneca; National Heart, Lung and Blood Institute (ACCORD and SPRINT) FX Editorial support for the preparation of this manuscript was provided by Richard M. Edwards, PhD, and Janet E. Matsuura, PhD, from Complete Healthcare Communications, Inc., with funding from Bristol-Myers Squibb and AstraZeneca.; Jan Basile, MD has received grant/research support from the National Heart, Lung and Blood Institute (ACCORD and SPRINT). Dr Basile is a consultant for Daiichi-Sankyo, Forest, Novartis, and Takeda, and is on the speakers' bureaus for AstraZeneca, Daiichi-Sankyo, Forest, and Novartis. NR 75 TC 4 Z9 7 U1 0 U2 7 PU JTE MULTIMEDIA PI BERWYN PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD JUL PY 2011 VL 123 IS 4 BP 38 EP 45 DI 10.3810/pgm.2011.07.2302 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 983DO UT WOS:000307098600004 PM 21680987 ER PT J AU Beckley, EH Scibelli, AC Finn, DA AF Beckley, Ethan H. Scibelli, Angela C. Finn, Deborah A. TI Progesterone receptor antagonist CDB-4124 increases depression-like behavior in mice without affecting locomotor ability SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Premenstrual syndrome; Postpartum depression; CDB-4124; Mifepristone; Forced swim test; Progesterone receptors; Allopregnanolone ID FORCED-SWIM TEST; PREMENSTRUAL DYSPHORIC DISORDER; FEMALE RATS; GLUCOCORTICOID-RECEPTOR; GENE-EXPRESSION; SEX-DIFFERENCES; ESTROUS-CYCLE; WISTAR RATS; MIFEPRISTONE; WITHDRAWAL AB Progesterone withdrawal has been proposed as an underlying factor in premenstrual syndrome and postpartum depression. Progesterone withdrawal induces forced swim test (FST) immobility in mice, a depression-like behavior, but the contribution of specific receptors to this effect is unclear. The role of progesterone's GABA(A) receptor-modulating metabolite allopregnanolone in depression- and anxiety-related behaviors has been extensively documented, but little attention has been paid to the role of progesterone receptors. We administered the classic progesterone receptor antagonist mifepristone (RU-38486) and the specific progesterone receptor antagonist CDB-4124 to mice that had been primed with progesterone for five days, and found that both compounds induced FST immobility reliably, robustly, and in a dose-dependent fashion. Although CDB-4124 increased FST immobility, it did not suppress initial activity in a locomotor test. These findings suggest that decreased progesterone receptor activity contributes to depression-like behavior in mice, consistent with the hypothesis that progesterone withdrawal may contribute to the symptoms of premenstrual syndrome or postpartum depression. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Beckley, Ethan H.; Scibelli, Angela C.; Finn, Deborah A.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Finn, Deborah A.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Beckley, EH (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, 3181 SW Sam Jackson Pk Rd,Mail Code L-470, Portland, OR 97239 USA. EM beckleye@ohsu.edu FU National Institutes of Health [AA010760, AA012439, T32-AA07468, F31-MH081560, F31-AA018043]; Department of Veterans Affairs; N.L. Tartar Research Fellowship; American Psychological Foundation/Council of Graduate Departments of Psychology; ARCS Foundation FX Major funding was provided by grants AA010760, AA012439, T32-AA07468, F31-MH081560, and F31-AA018043 from the National Institutes of Health, and a Merit Review Grant from the Department of Veterans Affairs. Additional support was provided by the N.L. Tartar Research Fellowship, the American Psychological Foundation/Council of Graduate Departments of Psychology Graduate Research Scholarship, and by the Nancy and Dodd Fischer Scholarship from the ARCS Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, the National Institute on Alcohol Abuse and Alcoholism, the National Institutes of Health, or other granting agencies. Granting agencies had no further role in experimental design, implementation, analysis, interpretation, or in any other aspect of the experiments reported currently. NR 63 TC 4 Z9 4 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JUL PY 2011 VL 36 IS 6 BP 824 EP 833 DI 10.1016/j.psyneuen.2010.11.004 PG 10 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 785OE UT WOS:000292237500007 PM 21163582 ER PT J AU De Yang, F Wang, XQ Liu, XP Zhao, KX Fu, WH Hao, XR Zhang, XL Huang, GS Qu, SC Bai, JS Huang, XF Kosten, TR Zhang, XY AF De Yang, Fu Wang, Xiang Qun Liu, Xiu Ping Zhao, Ke Xin Fu, Wei Hong Hao, Xue Ru Zhang, Xing Li Huang, Guo Shu Qu, Sheng Cai Bai, Jing Shen Huang, Xu Feng Kosten, Thomas R. Zhang, Xiang Yang TI Sex difference in QTc prolongation in chronic institutionalized patients with schizophrenia on long-term treatment with typical and atypical antipsychotics SO PSYCHOPHARMACOLOGY LA English DT Article DE Schizophrenia; Antipsychotics; QT prolongation; Electrocardiography ID TORSADE-DE-POINTES; INTERVAL PROLONGATION; VENTRICULAR REPOLARIZATION; ANTIDEPRESSANT DRUGS; PSYCHIATRIC-PATIENTS; SUDDEN-DEATH; CLOZAPINE; ABNORMALITIES; ASSOCIATION; PARAMETERS AB Objective The rate-corrected electrocardiographic QT (QTc) interval may significantly increase in patients with schizophrenia taking antipsychotics. The objective of this naturalistic study was to assess the prevalence of prolonged QTc interval in a large population of inpatients with chronic schizophrenia and to explore QTc relationship with demographic variables and prescribed treatments. Materials and methods Electrocardiograms were obtained from age-and sex-matched 456 controls and 1,006 inpatients with schizophrenia (male/female= 689/317) taking antipsychotics. QTc prolongation was defined as a mean value of two standard deviations above the controls. The adjusted relative risk was calculated using logistic regression analysis. Results QTc prolongation was present in 45 (4.5%) of 1,006 patients overall. Fewer men (3.2%, 22 of 689) than women (7.3%, 23 of 317) displayed QTc prolongation (p<0.004). Moreover, QTc intervals were shorter in male (391 +/- 31 ms) than female subjects (400 +/- 37 ms) (p<0.001). Clozapine was found to produce a longer QTc intervals compared to risperidone and typical antipsychotics. Furthermore, multiple regression analysis showed that significant predictors for QTc prolongation were comorbid cardiovascular disease, antipsychotic types, sex, and age (all p<0.01). Conclusion Our present findings suggest that there are sex differences in the prevalence of QTc prolongation and QTc lengthening in schizophrenia. Antipsychotic types are risk factors for QTc prolongation, and risks are substantially higher for clozapine. C1 [De Yang, Fu; Wang, Xiang Qun; Liu, Xiu Ping; Zhao, Ke Xin; Fu, Wei Hong; Hao, Xue Ru; Zhang, Xing Li; Huang, Guo Shu; Qu, Sheng Cai; Bai, Jing Shen] Beijing HuiLongGuan Hosp, Beijing 100096, Peoples R China. [Huang, Xu Feng] Univ Wollongong, Sch Hlth Sci, Ctr Translat Neurosci, Wollongong, NSW, Australia. [Kosten, Thomas R.; Zhang, Xiang Yang] VA Med Ctr, Houston, TX 77030 USA. [Kosten, Thomas R.; Zhang, Xiang Yang] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP De Yang, F (reprint author), Beijing HuiLongGuan Hosp, Beijing 100096, Peoples R China. EM yangfd200@126.com; kosten@bcm.edu; xyzhang@bcm.edu RI Huang, Xu-Feng/D-6053-2013; Huang, Xu-Feng/H-7408-2015 OI Huang, Xu-Feng/0000-0002-5895-2253 FU Stanley Medical Research Institute [03T-459, 05T-726]; United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX This study was funded by the Stanley Medical Research Institute (03T-459 and 05T-726) and the United States National Institute of Health (K05-DA0454, P50-DA18827, and U01-MH79639). NR 37 TC 1 Z9 1 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 2011 VL 216 IS 1 BP 9 EP 16 DI 10.1007/s00213-011-2188-5 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 782WI UT WOS:000292043000002 ER PT J AU Tanabe, J Nyberg, E Martin, LF Martin, J Cordes, D Kronberg, E Tregellas, JR AF Tanabe, Jody Nyberg, Eric Martin, Laura F. Martin, Jesse Cordes, Dietmar Kronberg, Eugene Tregellas, Jason R. TI Nicotine effects on default mode network during resting state SO PSYCHOPHARMACOLOGY LA English DT Article DE Resting-state networks; Default mode network; Nicotine; Attention; Posterior cingulate; Extra-striate cortex ID FUNCTIONAL CONNECTIVITY; SPATIAL ATTENTION; VISUOSPATIAL ATTENTION; VISUAL-ATTENTION; CINGULATE CORTEX; PARIETAL CORTEX; TOP-DOWN; BRAIN; FMRI; SCHIZOPHRENIA AB The default mode network (DMN), one of several resting-state networks (RSN) in the brain, is thought to be involved in self-referential thought, awareness, and episodic memories. Nicotine improves cognitive performance, in part by improving attention. Nicotinic agonists have been shown to decrease activity in regions within DMN and increase activity in regions involved in visual attention during effortful processing of external stimuli. It is unknown if these pharmacological effects also occur in the absence of effortful processing. This study aims to determine if nicotine suppresses activity in default mode and enhances activity in extra-striate RSNs in the absence of an external visual task. Within-subject, single-blinded, counterbalanced study of 19 non-smoking subjects who had resting functional MRI scans after 7 mg nicotine or placebo patch. Group independent component analysis was performed. The DMN component was identified by spatial correlation with a reference DMN mask. A visual attention component was identified by spatial correlation with an extra-striate mask. Analyses were conducted using statistical parametric mapping. Nicotine was associated with decreased activity in regions within the DMN and increased activity in extra-striate regions. Suppression of DMN and enhancement of extra-striate resting-state activity in the absence of visual stimuli or effortful processing suggest that nicotine's cognitive effects may involve a shift in activity from networks that process internal to those that process external information. This is a potential mechanism by which cholinergic agonists may have a beneficial effect in diseases associated with altered resting-state activity. C1 [Tanabe, Jody; Nyberg, Eric; Cordes, Dietmar] Univ Colorado Denver, Sch Med, Dept Radiol, Denver, CO USA. [Tanabe, Jody; Martin, Laura F.; Martin, Jesse; Kronberg, Eugene; Tregellas, Jason R.] Univ Colorado Denver, Sch Med, Dept Psychiat, Denver, CO USA. [Martin, Laura F.; Tregellas, Jason R.] Denver VA Med Ctr, Res Serv, Denver, CO USA. RP Tanabe, J (reprint author), 12700 E 19th Ave,Mailstop C278, Aurora, CO 80045 USA. EM jody.tanabe@ucdenver.edu RI Tregellas, Jason/J-3637-2015 FU NIH [R21DA024104, R01DA027748]; VA Biomedical Laboratory and Clinical Science Research and Development Service FX This publication was made possible by NIH Grant Numbers R21DA024104, R01DA027748 and the VA Biomedical Laboratory and Clinical Science Research and Development Service. We thank Dr. Robert Freedman for his helpful discussion. NR 39 TC 46 Z9 47 U1 1 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 2011 VL 216 IS 2 BP 287 EP 295 DI 10.1007/s00213-011-2221-8 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 782WL UT WOS:000292043300012 PM 21331518 ER PT J AU Ekundayo, OJ Vassar, SD Williams, LS Bravata, DM Cheng, EM AF Ekundayo, Olaniyi James Vassar, Stefanie D. Williams, Linda S. Bravata, Dawn M. Cheng, Eric M. TI Using Administrative Databases to Calculate Framingham Scores Within a Large Health Care Organization SO STROKE LA English DT Article DE administrative database; Framingham calculator; stroke ID TRANSIENT ISCHEMIC ATTACK; CARDIOVASCULAR RISK; VETERANS-AFFAIRS; STROKE RISK; ATHEROSCLEROSIS RISK; PREDICTION; VALIDATION; HYPERTENSION; ASSOCIATION; COMMUNITIES AB Background and Purpose-Framingham calculators are typically implemented in 1-on-1 settings to determine if a patient is at high risk for development of cardiovascular disease in the next 10 years. Because health care administrative datasets are including more clinical information, we explored how well administrative data-derived Framingham scores could identify persons who would have stroke develop in the next year. Methods-Using a nested case-control design, we compared all 313 persons who had a first-time stroke at 5 Veterans Administration Medical Centers with a random sample of 25 361 persons who did not have a first-time stroke in 2008. We compared Framingham scores and risk using administrative data available at the end of 2007. Results-Stroke patients had higher risk profile than controls: older age, higher systolic blood pressure and total cholesterol, more likely to have diabetes, cardiovascular disease, left ventricular hypertrophy, and more likely to use treatment for blood pressure (P<0.05). The mean Framingham generalized cardiovascular disease score (18.0 versus 14.5) as well as the mean Framingham stroke-specific score (13.2 versus 10.2) was higher for stroke cases than controls (both P<0.0001). The c-statistic for the generalized cardiovascular disease score was 0.68 (95% CI, 0.65-0.70) and for the stroke score was 0.64 (95% CI, 0.62-0.67). Conclusions-Persons who had a stroke develop in the next year had a worse Framingham risk profile, as determined by administrative data. Future studies should examine how to improve the stroke predictive tools and to identify the appropriate populations and uses for applying stroke risk predictive tools. (Stroke. 2011; 42: 1982-1987.) C1 [Cheng, Eric M.] VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA 90073 USA. [Ekundayo, Olaniyi James; Vassar, Stefanie D.; Cheng, Eric M.] Univ Calif Los Angeles, Los Angeles, CA USA. [Williams, Linda S.; Bravata, Dawn M.] VA HSR&D Ctr Excellence Implementing Evidence Bas, Richard L Roudebush VA Med Ctr, Indianapolis, IN USA. [Williams, Linda S.; Bravata, Dawn M.] Indiana Univ Sch Med, Indianapolis, IN USA. [Williams, Linda S.; Bravata, Dawn M.] Regenstrief Inst Hlth Care, Indianapolis, IN USA. RP Cheng, EM (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Neurol, 11301 Wilshire Blvd,ML 127, Los Angeles, CA 90073 USA. EM eric.cheng@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Quality Enhancement Research Initiative [08-242]; National Institute of Health/National Institute of Neurological Disorders and Stroke [K23NS058571]; American Heart Association Pharmaceutical Roundtable and David and Stevie Spina FX The project reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Quality Enhancement Research Initiative Project 08-242. Dr Cheng is supported by a career development award from National Institute of Health/National Institute of Neurological Disorders and Stroke (K23NS058571). Drs Cheng and Ekundayo are also supported by an award from the American Heart Association Pharmaceutical Roundtable and David and Stevie Spina. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 21 TC 5 Z9 5 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JUL PY 2011 VL 42 IS 7 BP 1982 EP 1987 DI 10.1161/STROKEAHA.110.603340 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 783NQ UT WOS:000292090900044 PM 21546488 ER PT J AU Soldin, OP Brent, GA Kloos, RT AF Soldin, Offie P. Brent, Gregory A. Kloos, Richard T. TI Publication of Industry-Sponsored Medical Research: Guidelines from the Consortium of Laboratory Medicine Journal Editors SO THYROID LA English DT Editorial Material C1 [Soldin, Offie P.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div,Dept Med, Los Angeles, CA 90095 USA. [Kloos, Richard T.] Ohio State Univ, Med Ctr, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Kloos, Richard T.] Ctr Comprehens Canc, Columbus, OH USA. RP Soldin, OP (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, LL S-166,3800 Reservoir Rd NW, Washington, DC 20057 USA. EM os35@georgetown.edu FU NIA NIH HHS [R01 AG033867] NR 2 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 1050-7256 J9 THYROID JI Thyroid PD JUL PY 2011 VL 21 IS 7 BP 693 EP 693 DI 10.1089/thy.2011.2107.ed2 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 784EW UT WOS:000292139300002 PM 21707435 ER PT J AU Zivkovic, SA Peltier, AC Iacob, T Lacomis, D AF Zivkovic, S. A. Peltier, A. C. Iacob, T. Lacomis, D. TI Chronic inflammatory demyelinating polyneuropathy and ventilatory failure: report of seven new cases and review of the literature SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Editorial Material DE chronic inflammatory demyelinating polyneuropathy; ventilatory failure; phrenic nerve ID GUILLAIN-BARRE-SYNDROME; PHRENIC-NERVE; RESPIRATORY-FAILURE; POLYRADICULONEUROPATHY; CIDP AB Background - Ventilatory involvement is rarely reported in chronic inflammatory demyelinating polyneuropathy (CIDP), but small prospective studies showed frequent involvement of phrenic nerves, which is usually overshadowed by severe limb weakness. Objectives - To report the clinical features of CIDP associated with ventilatory failure. Results - There were seven patients (43% women), with a mean age of 58.6 (range 38-82). The clinical courses were relapsing in five and progressive in two. Four patients had an initial event simulating Guillain-Barre syndrome (GBS). Ventilatory failure was recurrent in three patients. Five patients had full or nearly complete recoveries; one still requires nocturnal ventilation; and one died (14%) of myocardial infarction while still requiring mechanical ventilation. Conclusions- Clinical ventilatory dysfunction in CIDP is usually not an indicator of poor prognosis, and many patients recover without significant permanent disability. The mortality rate is similar to intubated patients with GBS. Patients with cardiopulmonary comorbidities and acute GBS-like onset of CIDP may be at higher risk of ventilatory failure which typically responds to 'standard' treatments of CIDP. Larger prospective studies are needed to define the prevalence, clinical spectrum and significance of ventilatory involvement in CIDP and to establish guidelines for evaluation and treatment. C1 [Zivkovic, S. A.; Lacomis, D.] Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA 15213 USA. [Zivkovic, S. A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Peltier, A. C.] Vanderbilt Univ, Dept Neurol, Nashville, TN USA. [Iacob, T.] Gottlieb Mem Hosp, Melrose Pk, IL USA. [Lacomis, D.] Univ Pittsburgh, Med Ctr, Dept Pathol Neuropathol, Pittsburgh, PA 15213 USA. RP Zivkovic, SA (reprint author), Univ Pittsburgh, Med Ctr, Dept Neurol, 200 Lothrop St,PUH F878, Pittsburgh, PA 15213 USA. EM zivkovics@upmc.edu OI Peltier, Amanda/0000-0003-1097-7715 NR 22 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-6314 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD JUL PY 2011 VL 124 IS 1 BP 59 EP 63 DI 10.1111/j.1600-0404.2010.01431.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 774QE UT WOS:000291400400009 PM 21649602 ER PT J AU Crilly, JF Keefe, RH Volpe, F AF Crilly, John F. Keefe, Robert H. Volpe, Fred TI Use of Electronic Technologies to Promote Community and Personal Health for Individuals Unconnected to Health Care Systems SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID PUBLIC-HEALTH; CHILDREN; IMPLEMENTATION; INFORMATION; ADHERENCE; VIOLENCE; PROGRAM AB Ensuring health care services for populations outside the mainstream health care system is challenging for all providers. But developing the health care infrastructure to better serve such unconnected individuals is critical to their health care status, to third-party payers, to overall cost savings in public health, and to reducing health disparities. Our increasingly sophisticated electronic technologies offer promising ways to more effectively engage this difficult to reach group and increase its access to health care resources. This process requires developing not only newer technologies but also collaboration between community leaders and health care providers to bring unconnected individuals into formal health care systems. We present three strategies to reach vulnerable groups, outline benefits and challenges, and provide examples of successful programs. (Am J Public Health. 2011;101:1163-1167. doi:10.2105/AJPH.2010. 300003) C1 [Crilly, John F.] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. [Crilly, John F.] US Dept Vet Affairs, Canandaigua, NY USA. [Keefe, Robert H.] SUNY Buffalo, Sch Social Work, Buffalo, NY 14260 USA. [Volpe, Fred] Substance Abuse & Mental Hlth Serv Adm, Drug Free Commun Program, Leesburg, VA USA. RP Keefe, RH (reprint author), SUNY Buffalo, Sch Social Work, 685 Baldy Hall, Buffalo, NY 14260 USA. EM rhkeefe@buffalo.edu NR 47 TC 8 Z9 9 U1 0 U2 6 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 JUL PY 2011 VL 101 IS 7 BP 1163 EP 1167 DI 10.2105/AJPH.2010.300003 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 776DG UT WOS:000291514100007 PM 21566023 ER PT J AU Merkow, RP Bilimoria, KY McCarter, MD Cohen, ME Barnett, CC Raval, MV Caprini, JA Gordon, HS Ko, CY Bentrem, DJ AF Merkow, Ryan P. Bilimoria, Karl Y. McCarter, Martin D. Cohen, Mark E. Barnett, Carlton C. Raval, Mehul V. Caprini, Joseph A. Gordon, Howard S. Ko, Clifford Y. Bentrem, David J. TI Post-Discharge Venous Thromboembolism After Cancer Surgery Extending the Case for Extended Prophylaxis SO ANNALS OF SURGERY LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; MAJOR ABDOMINAL-SURGERY; RISK-FACTORS; PULMONARY-EMBOLISM; THROMBOSIS; CHEMOTHERAPY; DEATH; COST AB Objective: To (1) define the frequency of overall and postdischarge venous thromboembolism (VTE) after cancer surgery, (2) identify VTE risk for individual cancer operations, and (3) assess mortality rates in patients who experienced a VTE. Summary and Background Data: Cancer is a known risk factor for VTE but less is known about VTE risk after specific cancer operations. Moreover, most cancer patients routinely receive VTE prophylaxis postoperatively while in the hospital, but few receive prolonged prophylaxis despite strong evidence it reduces postdischarge events. Methods: From 211 ACS NSQIP hospitals, 44,656 patients undergoing surgery for 9 cancers were identified (2006-2008). The frequency of VTE within 30-days of surgery was evaluated by cancer site and categorized as occurring before or after discharge. Multivariable logistic regression models were constructed to assess risk factors associated with VTE. Results: VTE occurred in 1.6% of all patients, most frequently after esophagogastric (4.2%) and hepatopancreaticobiliary (3.6%) surgery. Overall, 33.4% of VTEs occurred postdischarge (from 17.9% for esophagogastric to 100% for endocrine operations). Factors associated with VTE were age (>= 65 years), cancer/procedure type, metastatic disease, congestive heart failure, body mass index (BMI; >= 25 kg/m(2)), ascites, thrombocytosis (> 400,000 cells/mm(3)), albumin (< 3.0 g/dL), and operation duration (> 2 hours; all P < 0.001). Overall VTE was significantly more likely after gastrointestinal, lung, prostate, and ovarian/uterine operations (all P < 0.001). In those experiencing a VTE, mortality increased over 6-fold (8.0% vs. 1.3%; P < 0.001). Conclusion: One-third of VTE events in cancer surgery patients occurred postdischarge. Postoperative VTE was associated with operation type. Routine postdischarge VTE prophylaxis should be considered for high-risk patients. C1 [Merkow, Ryan P.; Bilimoria, Karl Y.; Raval, Mehul V.; Bentrem, David J.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Jesse Brown VAMC, Chicago, IL 60611 USA. [Merkow, Ryan P.; McCarter, Martin D.; Barnett, Carlton C.] Univ Colorado, Dept Surg, Denver Sch Med, Aurora, CO USA. [Merkow, Ryan P.; Bilimoria, Karl Y.; Cohen, Mark E.; Raval, Mehul V.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Gordon, Howard S.] Univ Chicago, Pritzker Sch Med, Dept Surg, Chicago, IL 60637 USA. [Caprini, Joseph A.] Univ Illinois, Dept Med, Jesse Brown VAMC, Chicago, IL USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Merkow, RP (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Surg, Jesse Brown VAMC, 676 N St Clair St,Suite 650, Chicago, IL 60611 USA. EM R-Merkow@northwestern.edu RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954; Raval, Mehul/0000-0002-1527-2661 FU American College of Surgeons; Health Services Research Division, Department of Veterans Affairs FX Supported by the American College of Surgeons Clinical Scholars in Residence program (to R.P.M.) and Career Development Award from the Health Services Research Division, Department of Veterans Affairs (to D.J.B.). NR 33 TC 64 Z9 66 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JUL PY 2011 VL 254 IS 1 BP 131 EP 137 DI 10.1097/SLA.0b013e31821b98da PG 7 WC Surgery SC Surgery GA 777BQ UT WOS:000291588600022 PM 21527843 ER PT J AU Cadena, J Restrepo, MI AF Cadena, Jose Restrepo, Marcos I. TI Methicillin-Resistant Staphylococcus aureus Guidelines: A Myriad of Open Questions SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID CLINICAL-PRACTICE GUIDELINES; INFECTIOUS-DISEASES SOCIETY; VANCOMYCIN; PNEUMONIA; MULTICENTER; AMERICA C1 [Cadena, Jose] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX 78229 USA. [Cadena, Jose] S Texas Vet Hlth Care Syst, Dept Med, Hosp Epidemiol, San Antonio, TX USA. [Restrepo, Marcos I.] S Texas Vet Hlth Care Syst, Dept Med Pulm & Crit Care, VERDICT Res Ctr, San Antonio, TX USA. RP Cadena, J (reprint author), Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Dept Med, 7703 Floyd Curl Dr,MC 7881, San Antonio, TX 78229 USA. EM cadenazuluag@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 FU NHLBI NIH HHS [K23HL096054, K23 HL096054] NR 9 TC 2 Z9 2 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 2011 VL 53 IS 1 BP 97 EP U138 DI 10.1093/cid/cir278 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 776QA UT WOS:000291550700019 PM 21653313 ER PT J AU Borckardt, JJ Reeves, ST Beam, W Jensen, MP Gracely, RH Katz, S Smith, AR Madan, A Patterson, D George, MS AF Borckardt, Jeffrey J. Reeves, Scott T. Beam, Will Jensen, Mark P. Gracely, Richard H. Katz, Sophie Smith, Arthur R. Madan, Alok Patterson, David George, Mark S. TI A Randomized, Controlled Investigation of Motor Cortex Transcranial Magnetic Stimulation (TMS) Effects on Quantitative Sensory Measures in Healthy Adults Evaluation of TMS Device Parameters SO CLINICAL JOURNAL OF PAIN LA English DT Article DE transcranial magnetic stimulation; pain; motor cortex; TMS; thermal; theta ID CHRONIC NEUROPATHIC PAIN; THETA-BURST STIMULATION; BRAIN-STIMULATION; CORTICAL STIMULATION; RTMS; PERCEPTION; RELIEF; EXCITABILITY; THRESHOLDS; IMPROVEMENT AB Objectives: There is emerging evidence that transcranial magnetic stimulation (TMS) can produce analgesic effects in clinical samples and in healthy adults undergoing experimentally induced pain; and the field of minimally invasive brain stimulation for the management of pain is expanding rapidly. Although motor cortex is the most widely used cortical target for TMS in the management of neuropathic pain, few studies have systematically investigated the analgesic effects of a full range of device parameters to provide initial hints about what stimulation intensities and frequencies are most helpful (or even potentially harmful) to patients. Further, there is considerable inconsistency between studies with respect to laboratory pain measurement procedures, TMS treatment parameters, sophistication of the sham methods, and sample sizes. Methods: This study used a sham-controlled, within-subject, crossover design to examine the effects of 5 different TMS treatment parameters across several quantitative sensory measures in a sample of healthy adult volunteers. Sixty-five participants underwent quantitative sensory testing procedures pre and post-40-minutes of real and sham motor cortex TMS. TMS was delivered at 1 Hz 80% resting motor threshold (rMT), 1 Hz 100% rMT, 10 Hz 80% rMT, 10 Hz 100% rMT, or 50 Hz triplets at 90% of active motor threshold (intermittent theta-burst). Results: The mean painfulness rating of real TMS stimulation itself was 3.0 (SE = 0.36) out of 10 and was significantly greater than zero [t(64) = 8.17, P < 0.0001]. The sham TMS methods used permitted matching between real and sham TMS-induced scalp sensations and participants were successfully blinded to condition (real versus sham). Findings suggest that the effects of motor cortex TMS on quantitative sensory tests in healthy adults vary across different treatment parameters with the smallest observed effect for intermittent theta-burst stimulation (Cohen's d = 0.03) and the largest for 10 Hz 100% rMT (d = 0.34). Discussion: Overall, TMS was associated with statistically significant effects on warm and cool sensory thresholds, cold pain thresholds, suprathreshold stimulus unpleasantness ratings, and wind-up pain. With respect to device parameter effects, higher frequency stimulation seems to be associated with the most analgesic and antisensitivity effects with the exception of intermittent theta-burst stimulation. The present findings support several clinical research findings suggesting that higher TMS frequencies tend to be associated with the most clinical benefit in patients with chronic pain. C1 [Borckardt, Jeffrey J.; Katz, Sophie; Madan, Alok; George, Mark S.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Borckardt, Jeffrey J.; Reeves, Scott T.; Beam, Will; Smith, Arthur R.] Med Univ S Carolina, Dept Anesthesiol & Perioperat Med, Charleston, SC 29425 USA. [George, Mark S.] Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. [George, Mark S.] Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. [Jensen, Mark P.; Patterson, David] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. [Gracely, Richard H.] Univ N Carolina, Sch Dent, Dept Endodont, Ctr Neurosensory Disorders, Chapel Hill, NC USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Borckardt, JJ (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St,IOP,5 North,518, Charleston, SC 29425 USA. EM borckard@musc.edu FU NINDS NIH HHS [K23 NS050485-03, K23 NS050485, K23 NS050485-04, K23 NS050485-01A2, K23 NS050485-02] NR 56 TC 18 Z9 20 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-8047 J9 CLIN J PAIN JI Clin. J. Pain PD JUL-AUG PY 2011 VL 27 IS 6 BP 486 EP 494 DI 10.1097/AJP.0b013e31820d2733 PG 9 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 774YR UT WOS:000291423200003 PM 21415720 ER PT J AU Billings, CJ Tremblay, KL Miller, CW AF Billings, Curtis J. Tremblay, Kelly L. Miller, Christi W. TI Aided cortical auditory evoked potentials in response to changes in hearing aid gain SO INTERNATIONAL JOURNAL OF AUDIOLOGY LA English DT Article DE Cortical auditory evoked potentials (CAEPs); Event-related potentials (ERPs); Signals in noise; Signal-to-noise ratio (SNR); N1; Auditory cortex; Hearing aids; Amplification ID TO-NOISE RATIO; STIMULUS-INTENSITY; SPEECH SOUNDS; INFANTS AB Objective : There is interest in using cortical auditory evoked potentials (CAEPs)to evaluate hearing aid fittings and experience-related plasticity associated with amplification; however, little is known about hearing aid signal processing effects on these responses. The purpose of this study was to determine the effect of clinically relevant hearing aid gain settings, and the resulting in-the-canal signal-to-noise ratios (SNRs), on the latency and amplitude of P1, N1, and P2 waves. Design & Sample : Evoked potentials and in-the-canal acoustic measures were recorded in nine normal-hearing adults in unaided and aided conditions. In the aided condition, a 40-dB signal was delivered to a hearing aid programmed to provide four levels of gain (0, 10, 20, and 30 dB). As a control, unaided stimulus levels were matched to aided condition outputs (i.e. 40, 50, 60, and 70 dB)for comparison purposes. Results : When signal levels are defined in terms of output level, aided CAEPs were surprisingly smaller and delayed relative to unaided CAEPs, probably resulting from increases to noise levels caused by the hearing aid. Discussion : These results reinforce the notion that hearing aids modify stimulus characteristics such as SNR, which in turn affects the CAEP in a way that does not reliably reflect hearing aid gain. C1 [Billings, Curtis J.] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR 97239 USA. [Billings, Curtis J.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. [Tremblay, Kelly L.; Miller, Christi W.] Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA. RP Billings, CJ (reprint author), Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, 3710 SW US Vet Hosp Rd NCRAR, Portland, OR 97239 USA. EM curtis.billings2@va.gov FU National Institutes of Health through the National Institute on Deafness and Other Communication Disorders; Department of Veterans Affairs through the Rehabilitation Research and Development Service [F31-DC007296, C6971M, R01-DC007705, P30-DC004661] FX The authors wish to thank Pamela Souza for helpful discussions about these data, and Wendy Tolin for assistance with data processing. This work was supported by the National Institutes of Health through the National Institute on Deafness and Other Communication Disorders, and the Department of Veterans Affairs through the Rehabilitation Research and Development Service [F31-DC007296 and C6971M (CJB); R01-DC007705 (KLT); P30-DC004661]. NR 28 TC 14 Z9 19 U1 1 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1499-2027 J9 INT J AUDIOL JI Int. J. Audiol. PD JUL PY 2011 VL 50 IS 7 BP 459 EP 467 DI 10.3109/14992027.2011.568011 PG 9 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 776RB UT WOS:000291553800004 PM 21486122 ER PT J AU Condray, R Dougherty, GG Keshavan, MS Reddy, RD Haas, GL Montrose, DM Matson, WR McEvoy, J Kaddurah-Daouk, R Yao, JK AF Condray, Ruth Dougherty, George G., Jr. Keshavan, Matcheri S. Reddy, Ravinder D. Haas, Gretchen L. Montrose, Debra M. Matson, Wayne R. McEvoy, Joseph Kaddurah-Daouk, Rima Yao, Jeffrey K. TI 3-Hydroxykynurenine and clinical symptoms in first-episode neuroleptic-naive patients with schizophrenia SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Cognition; first-episode psychosis; 3-hydroxykynurenine; neuroleptic-naive; neurological symptoms; schizophrenia; tryptophan ID ENDOGENOUS KYNURENIC ACID; GLOBAL BIOCHEMICAL APPROACH; NMDA RECEPTOR; CEREBROSPINAL-FLUID; GLYCINE SITE; BRAIN; RAT; PSYCHOSIS; SCALE; SIGNS AB One branch of the tryptophan catabolic cascade is the kynurenine pathway, which produces neurotoxic [3-hydroxykynurenine (3-OHKY), quinolinic acid] and neuroinhibitory (kynurenic acid) compounds. Kynurenic acid acts as a competitive antagonist at the glycine site of N-methyl-D-asparate receptors at high concentrations and as a non-competitive antagonist on the alpha(7)-nicotinic acetylcholine receptor at low concentrations. Kynurenine compounds also influence cognitive functions known to be disrupted in schizophrenia. Alterations in tryptophan metabolism are therefore of potential significance for the pathophysiology of this disorder. In this paper, tryptophan metabolites were measured from plasma using high-pressure liquid chromatography coupled with electrochemical coulometric array detection, and relationships were tested between these metabolic signatures and clinical symptoms for 25 first-episode neuroleptic-naive schizophrenia patients. Blood samples were collected and clinical and neurological symptoms were rated at baseline and again at 4 wk following initiation of treatment. Level of 3-OHKY and total clinical symptom scores were correlated when patients were unmedicated and neuroleptic-naive, and this relationship differed significantly from the correlation observed for patients 4 wk after beginning treatment. Baseline psychosis symptoms were predicted only by neurological symptoms. Moreover, baseline 3-OHKY predicted clinical change at 4 wk, with the lowest concentrations of 3-OHKY being associated with the greatest improvement in symptoms. Taken together, our findings suggest a neurotoxic product of tryptophan metabolism, 3-OHKY, predicts severity of clinical symptoms during the early phase of illness and before exposure to antipsychotic drugs. Baseline level of 3-OHKY may also predict the degree of clinical improvement following brief treatment with antipsychotics. C1 [Condray, Ruth; Dougherty, George G., Jr.; Reddy, Ravinder D.; Haas, Gretchen L.; Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. [Condray, Ruth; Dougherty, George G., Jr.; Keshavan, Matcheri S.; Reddy, Ravinder D.; Haas, Gretchen L.; Montrose, Debra M.; Yao, Jeffrey K.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. [Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Keshavan, Matcheri S.] Harvard Univ, Dept Psychiat, Boston, MA 02115 USA. [Matson, Wayne R.] Bedford VA Med Ctr, Med Res Serv, Bedford, MA USA. [McEvoy, Joseph] John Umstead Hosp, Dept Psychiat, Butner, NC USA. [McEvoy, Joseph; Kaddurah-Daouk, Rima] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst 151U II, Neurochem & Psychopharmacol Lab, Bldg 13,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM jkyao@pitt.edu FU GlaxoSmithKline; Department of Veterans Affairs; Veterans Health Administration; Office of Research and Development, Biomedical Laboratory R D; VA Pittsburgh Healthcare System; National Institute of Mental Health [MH58141, MH64118, MH45203, MH84941]; National Institute of General Medical Sciences [R24 GM078233] FX This material is based on work supported by grants from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory R & D [Merit Reviews (J.K.Y.) and Senior Research Career Scientist Award (J.K.Y.)], VA Pittsburgh Healthcare System (J.K.Y., G.G.D., R.D.R.), National Institute of Mental Health [MH58141 (J.K.Y.), MH64118 (R. D. R.), MH45203 (M. S. K), and MH84941 (R. K. D.)], National Institute of General Medical Sciences [R24 GM078233 (R. K. D.)]. The authors are grateful to Dr Nina Schooler and Dr Cameron Carter, and the clinical core staff of the Center for the Neuroscience of Mental Disorders (MH45156, David Lewis, M. D., Director) for their assistance in diagnostic and psychopathological assessments, and to P. Cheng, C. Korbanic and J. Haflett for their technical assistance. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government.; Dr McEvoy received honoraria from Lilly, and grant support from GlaxoSmithKline, Pfizer and Dainippon Sumitomo Pharmaceuticals America. Dr Kaddurah-Daouk is an equity holder in Metabolon Inc., a biotechnology company in the metabolomics domain, and also holds patent in this field. NR 66 TC 32 Z9 34 U1 2 U2 8 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 JUL PY 2011 VL 14 IS 6 BP 756 EP 767 DI 10.1017/S1461145710001689 PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 777JF UT WOS:000291611000004 PM 21275080 ER PT J AU Clark, DG Kar, J AF Clark, David Glenn Kar, Jitesh TI Bias of quantifier scope interpretation is attenuated in normal aging and semantic dementia SO JOURNAL OF NEUROLINGUISTICS LA English DT Article DE Sentence comprehension; Semantic dementia; Aging; Quantifier scope ID PRIMARY-PROGRESSIVE-APHASIA; SENTENCE COMPREHENSION; LANGUAGE COMPREHENSION; EYE-MOVEMENTS; 3 VARIANTS; AMBIGUITIES; ABILITIES; DEFICITS; MEMORY AB Many sentences with two quantifiers exhibit a phenomenon known as "quantifier scope ambiguity." Consider the example A unicorn ran through every garden, which contains the quantifiers "a" and "every." Most speakers of English agree that it may refer to one or more than one unicorn. Very little previous work has evaluated the ability of brain-damaged or aphasic patients to interpret such sentences. We administered a sentence-reading task with picture verification to a group of semantic dementia patients (N = 5) and a matched group of cognitively normal controls (N = 23). Controls exhibited a tendency to interpret the word every as having wide scope regardless of the order of quantifiers, as evidenced by decreased reaction time and increased accuracy when verifying pictures that required this interpretation. This bias was attenuated by increasing age and by the presence of semantic dementia. Furthermore, higher FAS fluency scores were associated with slower responses and more errors, while higher semantic fluency scores were associated with the opposite pattern. These findings fit best with a model in which the initial products of linguistic analysis are underspecified and biases in their interpretation arise subsequently through frontally mediated logical or pragmatic reasoning. Published by Elsevier Ltd. C1 [Clark, David Glenn] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. [Clark, David Glenn] Birmingham VA Med Ctr, Birmingham, AL USA. [Kar, Jitesh] New York Med Coll, Dept Med, Valhalla, NY 10595 USA. RP Clark, DG (reprint author), Univ Alabama, Dept Neurol, 1720 7th Ave S,SC 620C, Birmingham, AL 35294 USA. EM dgclark@uab.edu FU UAB McKnight Brain Research Institute FX This work was supported by a pilot grant from the UAB McKnight Brain Research Institute. The authors would like to thank Dr. David Basilico for insightful comments on an earlier version of the manuscript. NR 50 TC 2 Z9 2 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0911-6044 J9 J NEUROLINGUIST JI J. Neurolinguist. PD JUL PY 2011 VL 24 IS 4 BP 401 EP 419 DI 10.1016/j.jneuroling.2011.01.002 PG 19 WC Linguistics; Neurosciences; Psychology, Experimental SC Linguistics; Neurosciences & Neurology; Psychology GA 776CL UT WOS:000291512000001 ER PT J AU Pugazhenthi, S Nair, S Velmurugan, K Liang, QL Mahalingam, R Cohrs, RJ Nagel, MA Gilden, D AF Pugazhenthi, Subbiah Nair, Sreekala Velmurugan, Kalpana Liang, Qiaoling Mahalingam, Ravi Cohrs, Randall J. Nagel, Maria A. Gilden, Don TI Varicella-Zoster Virus Infection of Differentiated Human Neural Stem Cells SO JOURNAL OF VIROLOGY LA English DT Article ID GANGLIA IN-VIVO; NEURONS; DNA; APOPTOSIS; QUANTITATION; EXPRESSION; LATENT; VZV AB Primary varicella-zoster virus (VZV) infection in humans produces varicella (chickenpox), after which the virus becomes latent in ganglionic neurons. Analysis of the physical state of viral nucleic acid and virus gene expression during latency requires postmortem acquisition of fresh human ganglia. To provide an additional way to study the VZV-host relationship in neurons, we developed an in vitro model of infected differentiated human neural stem cells (NSCs). NSCs were induced to differentiate in culture dishes coated with poly-L-lysine and mouse laminin in the presence of fibroblast growth factor 2 (FGF-2), nerve growth factor (NGF), brain-derived neurotropic factor (BDNF), dibutyryl cyclic AMP, and retinoic acid. Immunostaining with neuronal (MAP2a and beta-tubulin), astrocyte (GFAP), and oligodendrocyte (CNPase) markers revealed that differentiated neurons constituted approximately 90% of the cell population. These neurons were maintained in culture for up to 8 weeks. No cytopathic effect (CPE) developed in neurons infected with cell-free VZV (Zostavax vaccine) compared to human fetal lung fibroblasts infected with VZV. Weeks later, VZV DNA virus-specific transcripts (open reading frames [ORFs] 21, 29, 62, and 63) were detected in infected neurons, and dual immunofluorescence staining revealed the presence of VZV IE63 and gE exclusively in healthy-appearing neurons, but not in astrocytes. Neither the tissue culture medium nor a homogenate prepared from VZV-infected neurons produced a CPE in fibroblasts. VZV induced apoptosis in fibroblasts, as shown by activation of caspase 3 and by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, but not in neurons. This model provides a unique in vitro system to study the VZV-neuronal relationship. C1 [Nair, Sreekala; Liang, Qiaoling; Mahalingam, Ravi; Cohrs, Randall J.; Nagel, Maria A.; Gilden, Don] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO 80045 USA. [Mahalingam, Ravi; Cohrs, Randall J.; Gilden, Don] Univ Colorado, Sch Med, Dept Microbiol, Aurora, CO 80045 USA. [Pugazhenthi, Subbiah; Velmurugan, Kalpana] Univ Colorado, Sch Med, Dept Med, Aurora, CO 80045 USA. [Pugazhenthi, Subbiah; Velmurugan, Kalpana] Denver VA Med Ctr, Denver, CO USA. RP Gilden, D (reprint author), Univ Colorado, Sch Med, Dept Neurol, Mail Stop B182,12700 E 19th Ave, Aurora, CO 80045 USA. EM don.gilden@ucdenver.edu FU National Institutes of Health [AG006127, AG032958, NS067070]; Veterans Administration [NEUD-004-07F] FX This work was supported in part by Public Health Service grants AG006127 (D.G.), AG032958 (D.G., S.P., R.M., and R.J.C.), and NS067070 (M.A.N.) from the National Institutes of Health and Merit Review grant NEUD-004-07F from the Veterans Administration (S.P.). NR 22 TC 23 Z9 23 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2011 VL 85 IS 13 BP 6678 EP 6686 DI 10.1128/JVI.00445-11 PG 9 WC Virology SC Virology GA 775CG UT WOS:000291434300054 PM 21525352 ER PT J AU Heinze, E Chan, G Mory, R Khavari, R Alavi, A Chung, SY Nishimura, RN Weisbart, RH AF Heinze, Emil Chan, Grace Mory, Rachel Khavari, Raz Alavi, Asif Chung, Sue Y. Nishimura, Robert N. Weisbart, Richard H. TI Tumor suppressor and T-regulatory functions of Foxp3 are mediated through separate signaling pathways SO ONCOLOGY LETTERS LA English DT Article DE transcription factors; apoptosis; immune regulation ID METASTASIS IN-VIVO; TRANSCRIPTIONAL REPRESSOR; CANCER; APOPTOSIS; P53; ONCOGENE; CELLS AB Foxp3 is a nuclear transcription factor that is both a tumor suppressor factor and regulator of T-regulatory cell (Treg) function, and is a potential therapeutic target in both autoimmunity and cancer. In order to distinguish molecular pathways responsible for these separate Foxp3 functions, deletion mutants of Foxp3 proteins were transduced and analyzed for cytotoxic activity in human cancer cell lines Skov3, MDA-MB-231, MCF-7 and Jurkat. Human Foxp3 cDNA mutants were amplified and ligated to produce plasmids for direct cell transfection. Constructs were produced and confirmed by DNA sequencing. Lipofectamine 2000 was used for plasmid transfection. Foxp3 cells were then examined. The results of our experiments reveal retention of tumor suppressor function in the absence of NFAT binding and transcriptional activation required for Treg function. Our results have significant implications for the design of autoimmune and cancer therapies that target Foxp3 and Treg cells. C1 [Heinze, Emil; Mory, Rachel; Khavari, Raz; Alavi, Asif; Chung, Sue Y.] Olive View UCLA Med Ctr, Dept Med, Sylmar, CA 91342 USA. [Chan, Grace; Weisbart, Richard H.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Res, Sepulveda, CA 91343 USA. [Nishimura, Robert N.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. RP Weisbart, RH (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst 1, Dept Res, 16111 Plummer St, North Hills, CA 91343 USA. EM rweisbar@ucla.edu FU Veterans Affairs FX This study was supported by a grant from the Veterans Affairs (RHW). NR 17 TC 1 Z9 1 U1 0 U2 5 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1792-1074 J9 ONCOL LETT JI Oncol. Lett. PD JUL-AUG PY 2011 VL 2 IS 4 BP 665 EP 668 DI 10.3892/ol.2011.307 PG 4 WC Oncology SC Oncology GA 775ZD UT WOS:000291503300015 ER PT J AU Hubbard, CS Ornitz, E Gaspar, JX Smith, S Amin, J Labus, JS Kilpatrick, LA Rhudy, JL Mayer, EA Naliboff, BD AF Hubbard, Catherine S. Ornitz, Edward Gaspar, John X. Smith, Suzanne Amin, Jenny Labus, Jennifer S. Kilpatrick, Lisa A. Rhudy, Jamie L. Mayer, Emeran A. Naliboff, Bruce D. TI Modulation of nociceptive and acoustic startle responses to an unpredictable threat in men and women SO PAIN LA English DT Article DE Aversive threat; Nociception; Pain; Anxiety; Sex differences ID FLEXION REFLEX NFR; SHOCK-INDUCED HYPERALGESIA; PAIN PERCEPTION; SEX-DIFFERENCES; ANTICIPATORY ANXIETY; SCORING CRITERIA; MENSTRUAL-CYCLE; HEALTHY WOMEN; FEAR; STIMULATION AB The present study examined whether a moderately aversive abdominal threat would lead to greater enhancement in affect-and pain-related defensive responding as indexed by the acoustic startle reflex (ASR) and nociceptive flexion reflex (NFR) in women compared to men. We also predicted sex differences in threat-related autonomic arousal measured by skin conductance responses (SCRs) to acoustic startle and noxious sural nerve stimulation. Unpredictable threat was manipulated by alternating 30-second safe ("no abdominal stimulation will be given'') and threat ("abdominal stimulation may occur at anytime'') periods. The experiment consisted of 2 blocks, each containing 4 safe and 4 threat periods in which the ASR or NFR was randomly probed 9-21 seconds following period onset. Unpredictable abdominal threat potentiated both ASR and NFR responses compared to periods signaling safety. SCRs to acoustic startle probes and noxious sural nerve stimulation were also significantly elevated during the threat vs safe periods. No sex differences in ASR or startle-evoked SCRs emerged. However, nociceptive responding was moderated by sex; females showed significant increases in NFR magnitudes across both safe and threat periods compared to males. Females also showed greater threat-potentiated SCRs to sural nerve stimulation than males. Our findings indicate that both affect-and pain-related defense and arousal systems are strongly influenced by threat of an aversive, unpredictable event, a situation associated with anticipatory anxiety. Females, compared to males, showed greater nociceptive responding and pain modulation when exposed to an unpredictable threatening context, whereas affect-driven ASR responses showed no such sex differentiation. Published by Elsevier B.V. on behalf of International Association for the Study of Pain. C1 [Naliboff, Bruce D.] Univ Calif Los Angeles, CNS, Div Digest Dis, Los Angeles, CA 90095 USA. [Hubbard, Catherine S.; Kilpatrick, Lisa A.; Mayer, Emeran A.] Univ Calif Los Angeles, Dept Med Digest Dis, Los Angeles, CA 90095 USA. [Hubbard, Catherine S.; Naliboff, Bruce D.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Ornitz, Edward; Labus, Jennifer S.; Mayer, Emeran A.; Naliboff, Bruce D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Ornitz, Edward; Labus, Jennifer S.; Mayer, Emeran A.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. [Rhudy, Jamie L.] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA. [Mayer, Emeran A.] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90095 USA. RP Naliboff, BD (reprint author), Univ Calif Los Angeles, CNS, Div Digest Dis, CHS 47-122,MC 737818,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM naliboff@ucla.edu RI Kilpatrick, Lisa/E-6995-2015 OI Hubbard, Catherine/0000-0002-9139-2198 FU National Institutes of Health (NIH) [P50-DK64539, R24-AT002681, T32-DK07180-34]; VA Medical Research FX Special thanks to Bradford Lubell, Cathy Liu, Byron Alexander, and Melissa Alberto for their assistance. This research was supported by National Institutes of Health (NIH) Grants P50-DK64539, R24-AT002681, NIH GI Training Grant T32-DK07180-34, VA Medical Research, and a gift from the Virginia Friedhofer Charitable Trust. NR 51 TC 19 Z9 19 U1 4 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 2011 VL 152 IS 7 BP 1632 EP 1640 DI 10.1016/j.pain.2011.03.001 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 775PM UT WOS:000291474000028 PM 21477924 ER PT J AU Jackson, DO Mrug, S Cook, F Beidleman, W Cropsey, KL AF Jackson, Dorothy O. Mrug, Sylvie Cook, Foster Beidleman, William Cropsey, Karen L. TI Factors predicting substance dependence and psychotropic medication use among offenders in community corrections SO ADDICTIVE BEHAVIORS LA English DT Article DE Substance dependence; Mental illness; Co-occurring disorders; Risk factors; Community corrections ID MENTAL-DISORDERS; SELF-MEDICATION; HYPOTHESIS; SERVICES; SUICIDE; RISK; COD AB Co-occurring substance abuse and mental illness is prevalent among criminal offenders, but little is mown about risk factors for these co-occurring disorders (COD) in community corrections population. To identify risk factors for COD in community corrections offenders, we analyzed assessment data from 5,595 offenders maintained under community supervision at a substance use diversion program. Three groups, offenders with substance use disorders who were taking psychotropic medications (SUPM), offenders with a substance use disorder (SUD) only and controls were compared. Logistic regressions were used to identify predictors of SUPM versus SUD only and controls. SUPM status was predicted by being White or Female, having some medical insurance (private or government aided), being unemployed, prior history of abuse/trauma. and prior history of suicidal ideation or behavior. Offenders with substance use disorders and co-occurring psychiatric problems face salient social risk that may need to be targeted through integrated services. Published by Elsevier Ltd. C1 [Jackson, Dorothy O.; Mrug, Sylvie] Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. [Cook, Foster; Cropsey, Karen L.] Univ Alabama, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35209 USA. [Beidleman, William] Birmingham Vet Affairs Med Ctr, Mental Hlth Clin, Birmingham, AL 35233 USA. RP Jackson, DO (reprint author), Univ Alabama, Dept Psychol, 1300 Univ Blvd,CH415, Birmingham, AL 35294 USA. EM ocky_888@hotmail.com FU UAB Department of Psychiatry; Jefferson County, Alabama FX This study was supported by UAB Department of Psychiatry internal funding and Jefferson County, Alabama, both of whom had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report: or in the decision to submit the paper for publication. NR 19 TC 3 Z9 3 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JUL PY 2011 VL 36 IS 7 BP 755 EP 758 DI 10.1016/j.addbeh.2010.12.033 PG 4 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 771TA UT WOS:000291182400014 PM 21367532 ER PT J AU Li, YX Berenji, GR AF Li, Yuxin Berenji, Gholam R. TI Cutaneous Sarcoidosis Evaluated by FDG PET SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE cutaneous sarcoidosis; positron emission tomography; FDG ID CLINICAL MANAGEMENT; SCINTIGRAPHY; TOMOGRAPHY AB A 50-year-old man presented with initial complaints of diffuse skin pain and pruritus. Physical examination revealed scattered skin plaques and subcutaneous nodules with mild tenderness throughout the body. Skin biopsy demonstrated noncaseating epithelioid granulomas. Patient soon developed cough, fever with hot flashes, and shortness of breath on exertion. FDG PET/CT demonstrated diffuse cutaneous involvement throughout the body. Follow-up FDG PET/CT after treatment revealed a decrease in FDG uptake suggesting a good response to therapy. C1 [Berenji, Gholam R.] VA Greater Los Angeles Healthcare Syst, Nucl Med Serv 115, Dept Nucl Med, Los Angeles, CA 90073 USA. RP Berenji, GR (reprint author), VA Greater Los Angeles Healthcare Syst, Nucl Med Serv 115, Dept Nucl Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Gholam.Berenji@va.gov NR 14 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD JUL PY 2011 VL 36 IS 7 BP 584 EP 586 DI 10.1097/RLU.0b013e318217a67b PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 772XH UT WOS:000291271000026 PM 21637067 ER PT J AU Sockol, LE Epperson, CN Barber, JP AF Sockol, Laura E. Epperson, C. Neill Barber, Jacques P. TI A meta-analysis of treatments for perinatal depression SO CLINICAL PSYCHOLOGY REVIEW LA English DT Review DE Postpartum; Psychotherapy; Pregnancy; Treatment; Depression; Meta-analysis ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; POSTPARTUM DEPRESSION; POSTNATAL DEPRESSION; INTERPERSONAL PSYCHOTHERAPY; PSYCHOLOGICAL TREATMENT; PUBLICATION BIAS; PREGNANT-WOMEN; PREVALENCE; DISORDER AB This meta-analysis assessed efficacy of pharmacologic and psychological interventions for treatment of perinatal depression. A systematic review identified 27 studies, including open trials (n = 9), quasi-randomized trials (n = 2), and randomized controlled trials (n = 16) assessing change from pretreatment to posttreatment or comparing these interventions to a control group. Uncontrolled and controlled effect sizes were assessed in separate meta-analyses. There was significant improvement in depressive symptoms from pretreatment to posttreatment, with an uncontrolled overall effect size (Hedges' g) of 1.61 after removal of outliers and correction for publication bias. Symptom levels at posttreatment were below cutoff levels indicative of clinically significant symptoms. At posttreatment, intervention groups demonstrated significantly greater reductions in depressive symptoms compared to control groups, with an overall controlled effect size (Hedges' g) of 0.65 after removal of outliers. Individual psychotherapy was superior to group psychotherapy with regard to changes in symptoms from pretreatment to posttreatment. Interventions including an interpersonal therapy component were found to have greater effect sizes, compared to control conditions, than interventions including a cognitive-behavioral component. Implications of the findings for clinical practice and future research are discussed. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Sockol, Laura E.] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. [Epperson, C. Neill; Barber, Jacques P.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Epperson, C. Neill] Univ Penn, Dept Obstet Gynecol, Philadelphia, PA 19104 USA. [Barber, Jacques P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Sockol, LE (reprint author), Univ Penn, Dept Psychol, 3815 Walnut St, Philadelphia, PA 19104 USA. EM lsockol@sas.upenn.edu FU NIDA NIH HHS [K24 DA030301] NR 75 TC 78 Z9 78 U1 9 U2 56 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD JUL PY 2011 VL 31 IS 5 BP 839 EP 849 DI 10.1016/j.cpr.2011.03.009 PG 11 WC Psychology, Clinical SC Psychology GA 771VM UT WOS:000291188800012 PM 21545782 ER PT J AU Baker-LePain, JC Nakamura, MC Lane, NE AF Baker-LePain, Julie C. Nakamura, Mary C. Lane, Nancy E. TI Effects of inflammation on bone: an update SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE BMP pathway; bone loss; cytokine; inflammation; osteoblast; osteoclast; therapy; WNT pathway ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; EARLY RHEUMATOID-ARTHRITIS; COLLAGEN-INDUCED ARTHRITIS; INTERLEUKIN-12/23 MONOCLONAL-ANTIBODY; GROWTH-FACTOR-BETA; MINERAL-DENSITY; ANKYLOSING-SPONDYLITIS; TNF-ALPHA; RADIOGRAPHIC PROGRESSION; INTERFERON-BETA AB Purpose of review To present an updated summary of the relationship between inflammation and localized and generalized bone loss in the rheumatic diseases. Recent findings In addition to the well established role of inflammatory cytokines in promoting enhanced osteoclast function and bone loss, recent work has discovered the cytokine milieu may also inhibit osteoblast function and bone repair. The WNT and bone morphogenetic protein pathways provide molecular links between inflammation and altered bone homeostasis in chronic inflammatory states. These pathways and others have been the targets of emerging therapies for the management of inflammatory bone loss. Summary Inflammation and bone loss are linked through a number of molecular pathways. Both of these processes need to be addressed when designing an effective treatment strategy for the rheumatic diseases. C1 [Lane, Nancy E.] Univ Calif Davis, Med Ctr, Dept Internal Med, Ctr Healthy Aging, Sacramento, CA 95817 USA. [Nakamura, Mary C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Nakamura, Mary C.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Lane, NE (reprint author), Univ Calif Davis, Med Ctr, Dept Internal Med, Ctr Healthy Aging, Sacramento, CA 95817 USA. EM nelane@ucdavis.edu FU NIH [AR007304]; SOF; REF; UCSF [Lane K24, Lane R01, Lane R13 - AR04884, AR052000, AR043052]; Nakamura VA Merit Review, Department of Veteran's Affairs [R01 AR050038-01] FX This work was supported by the NIH Academic Rheumatology and Clinical Immunology Training Grant AR007304 to J.C.B. and by SOF, REF, UCSF training grant, Lane K24, Lane R01, Lane R13 - AR04884, AR052000, and AR043052 to N.E.L. Nakamura R01 AR050038-01 VA Merit Review, Department of Veteran's Affairs. NR 79 TC 23 Z9 24 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD JUL PY 2011 VL 23 IS 4 BP 389 EP 395 DI 10.1097/BOR.0b013e3283474dbe PG 7 WC Rheumatology SC Rheumatology GA 772OU UT WOS:000291244200012 PM 21532485 ER PT J AU Ahearn, EP Juergens, T Cordes, T Becker, T Krahn, D AF Ahearn, Eileen P. Juergens, Timothy Cordes, Timothy Becker, Tara Krahn, Dean TI A review of atypical antipsychotic medications for posttraumatic stress disorder SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Review DE atypical antipsychotics; pharmacologic treatment; posttraumatic stress disorder ID DOUBLE-BLIND; COMBAT VETERANS; OPEN-LABEL; ADULT-RAT; ADJUNCTIVE RISPERIDONE; PSYCHOTIC SYMPTOMS; OPEN TRIAL; OLANZAPINE; PLACEBO; PTSD AB Posttraumatic stress disorder (PTSD) can be a chronic and disabling illness with a limited response to antidepressant treatment, particularly in the case of combat-induced PTSD. The purpose of this study is to review randomized controlled and open-label trials of atypical antipsychotics for the treatment of PTSD. We conducted PUBMED and PILOTS database searches for clinical trials of atypical antipsychotic medications for PTSD in May 2010. Eighteen clinical trials (10 double-blind placebo-controlled, eight open-label) of atypical antipsychotics for PTSD were found and reviewed. Effect sizes of double-blind placebo-controlled trials were small, but were positive for risperidone and quetiapine. Intrusive and hypervigilance symptom subscales showed the most improvement. We concluded that atypical antipsychotic medications have a modest benefit for the treatment of PTSD. Larger randomized controlled trials are needed to clarify the potential utility of these medications in the treatment of PTSD and more rigorous examination of metabolic side effects is warranted. Int Clin Psychopharmacol 26:193-200 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Ahearn, Eileen P.; Juergens, Timothy; Krahn, Dean] Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. [Ahearn, Eileen P.; Juergens, Timothy; Cordes, Timothy; Krahn, Dean] Univ Wisconsin, Dept Psychiat, Madison, WI 53705 USA. [Becker, Tara] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53705 USA. RP Ahearn, EP (reprint author), Univ Wisconsin, VA Hosp, 2500 Overlook Terrace, Madison, WI 53705 USA. EM eileen.ahearn@va.gov NR 51 TC 13 Z9 14 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD JUL PY 2011 VL 26 IS 4 BP 193 EP 200 DI 10.1097/YIC.0b013e3283473738 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 774KD UT WOS:000291383200002 PM 21597381 ER PT J AU Fueki, K Igarashi, Y Maeda, Y Baba, K Koyano, K Akagawa, Y Sasaki, K Kuboki, T Kasugai, S Garrett, NR AF Fueki, K. Igarashi, Y. Maeda, Y. Baba, K. Koyano, K. Akagawa, Y. Sasaki, K. Kuboki, T. Kasugai, S. Garrett, N. R. TI Factors related to prosthetic restoration in patients with shortened dental arches: a multicentre study SO JOURNAL OF ORAL REHABILITATION LA English DT Article DE shortened dental arch; prosthetic treatment; occlusal unit; multicentre study ID REMOVABLE PARTIAL DENTURES; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; MISSING OCCLUSAL UNITS; MASTICATORY PERFORMANCE; ORAL FUNCTION; SATISFACTION; ABILITY; 5-YEAR AB P>The aim of this study was to identify the factors related to prosthetic restoration in patients with shortened dental arches (SDA). SDA patients with 2-12 missing occlusal units were consecutively enrolled from seven university-based dental hospitals in Japan. Of the 145 subjects (mean age; 63 center dot 4 years), 41% chose no treatment and 59% sought to replace their edentulous spaces with removable partial dentures or implant-supported fixed partial dentures. Restoration decisions were related to tooth loss patterns. Only 3% of subjects missing just second molar(s) sought to receive prosthetic treatment, while the percentage increased to 58% in subjects who were missing first and second molars and 93% in subjects missing premolar(s). Logistic regression analyses found that young age, increased number of missing occlusal units, asymmetric arch and presence of chewing complaint were significant predictors for prosthetic restoration (P < 0 center dot 05). Increased number of missing occlusal units and asymmetric arch were significant predictors for the presence of chewing complaint (P < 0 center dot 05). These results suggest that perceived impairment of chewing ability owing to missing occlusal units is a critical factor for prosthetic restoration in SDA patients. C1 [Fueki, K.; Igarashi, Y.] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Sect Removable Partial Denture Prosthodont, Tokyo 1138549, Japan. [Maeda, Y.] Osaka Univ, Grad Sch Dent, Div Oromaxillofacial Regenerat, Osaka, Japan. [Baba, K.] Showa Univ, Sch Dent, Dept Prosthodont, Tokyo 142, Japan. [Koyano, K.] Kyushu Univ, Div Oral Rehabil, Grad Sch Dent, Sect Removable Prosthodont, Kyushu, Japan. [Akagawa, Y.] Hiroshima Univ, Grad Sch Biomed Sci, Dept Adv Prosthodont, Hiroshima, Japan. [Sasaki, K.] Tohoku Univ, Grad Sch Dent, Div Adv Prosthet Dent, Sendai, Miyagi 980, Japan. [Kuboki, T.] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Oral Rehabil & Regenerat Med, Okayama, Japan. [Kasugai, S.] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Sect Oral Implantol & Regenerat Dent Med, Tokyo, Japan. [Garrett, N. R.] Univ Calif Los Angeles, Sch Dent, Jane & Jerry Weintraub Ctr Reconstruct Biotechnol, Los Angeles, CA 90024 USA. [Garrett, N. R.] Univ Calif Los Angeles, Sch Dent, Div Adv Prosthodont Biomat & Hosp Dent, Los Angeles, CA 90024 USA. [Garrett, N. R.] Vet Adm Greater Angeles Healthcare Syst, Los Angeles, CA USA. RP Fueki, K (reprint author), Tokyo Med & Dent Univ, Grad Sch, Sect Removable Partial Denture Prosthodont, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138549, Japan. EM kunfu.rpro@tmd.ac.jp RI Fueki, Kenji/A-9909-2008 OI Fueki, Kenji/0000-0002-5885-2447 FU Ministry of Education, Culture, Sports, Science and Technology of Japan [20249077] FX The authors thank collaborative researchers of this study, Drs. E. Yoshida, T. Sugiura, K. Ikebe, H. Tukasaki, Y. Ogino, S. Koyama, K. Koretake, and H. Arakawa for their kind assistance with data collection and analyses. This study was supported by a Grant-in-Aid for Scientific Research (A) (No. 20249077) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. There are no potential conflicts of interest. NR 27 TC 10 Z9 11 U1 0 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0305-182X J9 J ORAL REHABIL JI J. Oral Rehabil. PD JUL PY 2011 VL 38 IS 7 BP 525 EP 532 DI 10.1111/j.1365-2842.2010.02183.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 772ZK UT WOS:000291276600007 PM 21091529 ER PT J AU Page, ST Hirano, L Gilchriest, J Dighe, M Amory, JK Marck, BT Matsumoto, AM AF Page, Stephanie T. Hirano, Lianne Gilchriest, Janet Dighe, Manjiri Amory, John K. Marck, Brett T. Matsumoto, Alvin M. TI Dutasteride Reduces Prostate Size and Prostate Specific Antigen in Older Hypogonadal Men With Benign Prostatic Hyperplasia Undergoing Testosterone Replacement Therapy SO JOURNAL OF UROLOGY LA English DT Article DE testosterone; prostate; 5-alpha reductase inhibitors; dihydrotestosterone ID LOW SERUM TESTOSTERONE; LOWER URINARY-TRACT; EXOGENOUS TESTOSTERONE; ANDROGEN DEFICIENCY; CANCER; 5-ALPHA-REDUCTASE; FINASTERIDE; SYMPTOMS; PROGRESSION; PREDICTORS AB Purpose: Benign prostatic hyperplasia and hypogonadism are common disorders in aging men. There is concern that androgen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia. We examined whether combining dutasteride, which inhibits testosterone to dihydrotestosterone conversion, with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces androgenic stimulation of the prostate compared to testosterone alone. Materials and Methods: We conducted a double-blind, placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia, prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl (less than 9.7 nmol/l). Subjects were randomized to daily transdermal 1% T gel plus oral placebo or dutasteride for 6 months. Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl. The primary outcomes were prostate volume measured by magnetic resonance imaging, serum prostate specific antigen and androgen levels. Results: A total of 46 subjects completed all procedures. Serum testosterone increased similarly into the mid-normal range in both groups. Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group. In the testosterone plus dutasteride group prostate volume and prostate specific antigen (mean +/- SEM) decreased 12% +/- 2.5% and 35% +/- 5%, respectively, compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5% +/- 3.3% and 19% +/- 7% (p = 0.03 and p = 0.008), respectively, after 6 months of treatment. Prostate symptom scores improved in both groups. Conclusions: Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only. Coadministration of a 5 alpha-reductase inhibitor with testosterone appears to spare the prostate from androgenic stimulation during testosterone replacement in older, hypogonadal men with symptomatic benign prostatic hyperplasia. C1 [Page, Stephanie T.] Univ Washington, Sch Med, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98195 USA. [Dighe, Manjiri] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Hirano, Lianne; Gilchriest, Janet; Marck, Brett T.; Matsumoto, Alvin M.] Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. [Hirano, Lianne; Gilchriest, Janet; Marck, Brett T.; Matsumoto, Alvin M.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. RP Page, ST (reprint author), Univ Washington, Sch Med, Div Metab Endocrinol & Nutr, Dept Med, Box 3547138,1959 NE Pacific St, Seattle, WA 98195 USA. EM page@u.washington.edu FU GlaxoSmithKline FX Supported by an investigator initiated grant from GlaxoSmithKline. NR 26 TC 19 Z9 20 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2011 VL 186 IS 1 BP 191 EP 197 DI 10.1016/j.juro.2011.03.026 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 775PH UT WOS:000291472900058 PM 21575967 ER PT J AU Singh, JA Yang, S Strand, V Simon, L Forsythe, A Hamburger, S Chen, L AF Singh, Jasvinder A. Yang, Shuo Strand, Vibeke Simon, Lee Forsythe, Anna Hamburger, Steve Chen, Lang TI Validation of pain and patient global scales in chronic gout: data from two randomised controlled trials SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID CLINICALLY IMPORTANT DIFFERENCES; QUALITY-OF-LIFE; RHEUMATOID-ARTHRITIS; IMPORTANT DIFFERENCE; DEFINITION AB Objective To assess validity of pain and patient global scales in gout. Methods The authors used data from pegloticase clinical trials in chronic refractory gout to examine the validity of visual analogue scale (VAS) pain, Short-Form 36 (SF-36) bodily pain subscale and VAS patient global assessment (all scales 0-100). Convergent/divergent validity with clinical characteristics was tested by using Spearman's correlation coefficient. For discriminant ability, the authors compared the change at 6 months between placebo and pegloticase arms and calculated effect size (ES) and standardised response mean (SRM). Results 212 patients (mean age, 55.4 years, 82% men; 73% with tophaceous gout) provided data. VAS pain was statistically significantly correlated with tender joints (r = 0.42), swollen joints (r = 0.30), SF-36 physical (r = -0.56) and Mental Component Summary (r = -0.36) and Health Assessment Questionnaire scores (r = 0.54; all p-values <0.0001), but not disease duration (r = -0.01; p = 0.84), gout flares (r = 0.12; p = 0.08), comorbidities (r = 0.05; p = 0.47) or plasma urate (r = 0.01; p = 0.89). Similar and significant correlation coefficients with tender and swollen joints were noted for VAS patient global assessment (r = 0.35 and 0.23; p<0.0012 for both) and SF-36 pain subscale (r = -0.27 and -0.19; p<0.006 for both). Pegloticase group had significantly more improvement than placebo at 6 months, mean (SD): VAS pain, -9.2 (29.3) versus 1.9 (26.4), p = 0.0002; SF-36 pain, 14.6 (25.6) versus -0.04 (21.1), p<0.0001; and patient global, -9.3 (26.5) versus 3.4 (22.8), p<0.0001. ES and SRMs in pegloticase group were as follows: VAS pain, 0.34 and 0.30; SF-36 pain, 0.69 and 0.57; patient global, 0.49 and 0.44. Conclusion VAS pain, SF-36 pain and patient global VAS are valid outcome measures in patients with chronic gout. C1 [Singh, Jasvinder A.; Yang, Shuo; Chen, Lang] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. [Strand, Vibeke] Stanford Univ, Palo Alto, CA 94304 USA. [Simon, Lee] SDG LLC, Cambridge, MA USA. [Forsythe, Anna; Hamburger, Steve] Savient Pharmaceut Inc, E Brunswick, NJ USA. RP Singh, JA (reprint author), Univ Alabama, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com RI YANG, SHUO/D-2695-2014 OI YANG, SHUO/0000-0002-4999-0506; singh, jasvinder/0000-0003-3485-0006 FU University of Alabama; CRADA; Allergan; Takeda; Savient; Wyeth; Amgen FX This material is the result of work supported with University of Alabama grant to JAS and the resources and the use of facilities at the Birmingham VA Medical Center, Alabama, USA. Savient Pharmaceuticals and UAB are parties to a Clinical Research and Development Agreement (CRADA) that pertains to health-related quality of life studies in the area of gout. Funding from the CRADA was not used to support this project.; JAS has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth and Amgen; and consultant fees from Savient, URL Pharmaceuticals and Novartis. VS is a consultant for Savient and Novartis. LS is a consultant for Takeda, Horizon Pharma, Savient, Wyeth, Pfizer, Merck and Genzyme and is a member of the Board of Directors of Savient. SH and AF are employees of Savient Pharmaceuticals, Inc. SY and LC has no financial conflicts. NR 15 TC 9 Z9 10 U1 0 U2 7 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2011 VL 70 IS 7 BP 1277 EP 1281 DI 10.1136/ard.2010.144022 PG 5 WC Rheumatology SC Rheumatology GA 769PG UT WOS:000291028800017 PM 21622774 ER PT J AU Goebel-Stengel, M Stengel, A Tache, Y Reeve, JR AF Goebel-Stengel, Miriam Stengel, Andreas Tache, Yvette Reeve, Joseph R., Jr. TI The importance of using the optimal plasticware and glassware in studies involving peptides SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Test tube surface; Endocrine peptide; Radioimmunoassay; Iodinated peptide ID PROTEIN; PURIFICATION; ADSORPTION; GHRELIN; HORMONE; LOSSES; RATS AB The unpredictable nature of peptide binding to surfaces requires optimization of experimental containers to be used. To demonstrate the variable recoveries of peptides from multiple surfaces commonly employed in peptide research, we tested the recovery of radiolabeled 125I endocrine peptides under different conditions and provide guidelines for determining the surfaces to use for other peptides. (125)I-labeled peptides (ghrelin, sulfated cholecystokinin-8, corticotropin-releasing factor, glucagon-like peptide-1 [GLP-1], insulin, leptin, nesfatin-1, and peptide YY), representing a wide spectrum in net charge, size, end group, and modification, were incubated for 48 h in glass and plastic tubes untreated or coated with siliconizing fluid. Best surfaces were chosen and peptides were incubated with bovine serum albumin (BSA, 1%) with or without subsequent lyophilization. Recovery of (125)I-labeled peptides was determined by gamma counting. Important differences in (125)I-labeled peptide binding capacities to various types of surfaces exist. Siliconization decreased, whereas the addition of BSA improved recovery from surfaces tested. Lyophilizing solutions containing (125)I-labeled peptides and BSA in the tubes best suited for individual peptides rendered more than 89% recovery for all peptides. Ghrelin specifically displaced (125)I-ghrelin from borosilicate glass, whereas GLP-1 and Fmoc-arginine did not. Choosing the appropriate experimental container avoids unpredictable peptide loss that results in inaccurate measurements and false conclusions. (C) 2011 Elsevier Inc. All rights reserved. C1 [Goebel-Stengel, Miriam; Stengel, Andreas; Tache, Yvette; Reeve, Joseph R., Jr.] VA Greater Los Angeles Healthcare Syst, Peptid Radioimmunoassay & Prote Lab, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. [Goebel-Stengel, Miriam] Martin Luther Hosp, Dept Med, D-14193 Berlin, Germany. [Goebel-Stengel, Miriam] Martin Luther Hosp, Inst Neurogastroenterol, D-14193 Berlin, Germany. [Goebel-Stengel, Miriam; Stengel, Andreas; Tache, Yvette; Reeve, Joseph R., Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Stengel, Andreas] Univ Med Berlin, Dept Med, Div Psychosomat Med & Psychotherapy, D-10117 Berlin, Germany. RP Reeve, JR (reprint author), VA Greater Los Angeles Healthcare Syst, Peptid Radioimmunoassay & Prote Lab, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. EM jreeve@mednet.ucla.edu FU National Institutes of Health [DK-41301, RO1 DK-83449] FX This work was supported by National Institutes of Health Center Grant: CURE/Digestive Diseases Research Center Grant DK-41301 (Peptidomic RIA Proteomic Core (J.R.R. Jr.) and Animal Core (Y.T.)) and RO1 DK-83449 (J.R.R. Jr.). NR 16 TC 30 Z9 30 U1 4 U2 37 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUL 1 PY 2011 VL 414 IS 1 BP 38 EP 46 DI 10.1016/j.ab.2011.02.009 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 765KK UT WOS:000290704300006 PM 21315060 ER PT J AU Loftis, JM Choi, D Hoffman, W Huckans, MS AF Loftis, Jennifer M. Choi, Dongseok Hoffman, William Huckans, Marilyn S. TI Methamphetamine Causes Persistent Immune Dysregulation: A Cross-Species, Translational Report SO NEUROTOXICITY RESEARCH LA English DT Article DE Methamphetamine; Substance abuse; Adhesion molecules; Cytokines; Neuroinflammation; Chemokines ID PRO-INFLAMMATORY CYTOKINES; RECEPTOR MESSENGER-RNA; LONG-TERM POTENTIATION; NECROSIS-FACTOR-ALPHA; BLOOD-BRAIN-BARRIER; CHRONIC HEPATITIS-C; RECOGNITION MEMORY; STRUCTURAL ABNORMALITIES; REGIONAL HETEROGENEITY; DEPENDENT INDIVIDUALS AB Methamphetamine (MA) dependence causes serious cognitive impairments that can persist during abstinence and negatively affect recovery outcomes. Evidence suggests that immune factors, such as cytokines, chemokines, and cellular adhesion molecules, contribute to MA-induced immune dysfunction, neuronal injury, and persistent cognitive impairments, yet the role of MA-induced brain inflammation remains unclear. To address this question, we used a cross-species, translational approach. Thirty-two male C57BL/6J mice were administered MA (1 mg/kg) or saline subcutaneously for seven consecutive days. Mice were euthanized at 72 h or 3 weeks after the last drug dose, and blood and brain samples were collected. In addition, 20 adults in remission from MA dependence and 20 non-dependent controls completed neuropsychological assessments and a blood draw. Multiplex assays were used to measure cytokine, chemokine, and intercellular adhesion molecule (ICAM-1) expression in mouse and human samples. A number of significant MA-induced changes in neuroimmune factors were observed. Of particular interest were the chemokine monocyte chemoattractant protein 1 (MCP-1) and the cellular adhesion molecule ICAM-1, which were similarly increased in the plasma of MA exposed mice as well as humans. In human participants, MA-induced changes in the cytokine and chemokine milieu were accompanied by increased cognitive impairments. Mice showing MA-induced changes in peripheral immune molecule expression also had significant brain-region specific changes in pro-inflammatory cytokines, chemokines, and ICAM-1. This cross-species, translational study suggests that chronic CNS immune dysregulation may in part contribute to the longlasting neuropsychiatric consequences of MA dependence. C1 [Loftis, Jennifer M.; Hoffman, William; Huckans, Marilyn S.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA. [Choi, Dongseok] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Loftis, Jennifer M.; Hoffman, William; Huckans, Marilyn S.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. RP Loftis, JM (reprint author), Portland VA Med Ctr, Res & Dev Serv, 3710 SW US Vet Hosp Rd,R&D 16, Portland, OR 97239 USA. EM loftisj@ohsu.edu; Marilyn.huckans@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research, and Development and Clinical Sciences Research and Development; National Institute on Drug Abuse [P50 DA18165]; Methamphetamine Abuse Research Center at Oregon Health & Science University; Portland VAMC FX This material is based upon research in part supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research, and Development and Clinical Sciences Research and Development. Additional funding for this study was provided by the National Institute on Drug Abuse (P50 DA18165). The authors would like to thank the Methamphetamine Abuse Research Center at Oregon Health & Science University, and the Portland VAMC for providing research and administrative support. NR 68 TC 35 Z9 35 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PD JUL PY 2011 VL 20 IS 1 BP 59 EP 68 DI 10.1007/s12640-010-9223-x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 760IT UT WOS:000290318700007 PM 20953917 ER PT J AU Park, J Werner, RM AF Park, Jeongyoung Werner, Rachel M. TI CHANGES IN THE RELATIONSHIP BETWEEN NURSING HOME FINANCIAL PERFORMANCE AND QUALITY OF CARE UNDER PUBLIC REPORTING SO HEALTH ECONOMICS LA English DT Article DE nursing homes; financial performance; quality of care; report cards; pay-for-performance ID MEDICAID REIMBURSEMENT; CASE-MIX; OWNERSHIP; COMPETITION; TRENDS; IMPACT; PROFIT; COSTS AB The relationship between financial performance and quality of care in nursing homes is not well defined and prior work has been mixed. The recent focus on improving the quality of nursing homes through market-based incentives such as public reporting may have changed this relationship, as public reporting provides nursing homes with increased incentives to engage in quality-based competition. If quality improvement activities require substantial production costs, nursing home profitability may become a more important predictor of quality under public reporting. This study explores the relationship between financial performance and quality of care and test whether this relationship changes under public reporting. Using a 10-year (fiscal years 1997-2006) panel data set of 9444 skilled nursing facilities in the US, this study employs a facility fixed-effects with and without instrumental variables approach to test the effect of finances on quality improvement and correct for potential endogeneity. The results show that better financial performance, as reflected by the 1-year lagged total profit margin, is modestly associated with higher quality but only after public reporting is initiated. These findings have important policy implications as federal and state governments use market-based incentives to increase demand for high-quality care and induce providers to compete based on quality. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Park, Jeongyoung] Amer Board Internal Med, Philadelphia, PA 19106 USA. [Werner, Rachel M.] Philadelphia VAMC, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Werner, Rachel M.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Park, J (reprint author), Amer Board Internal Med, 510 Walnut St,Suite 1700, Philadelphia, PA 19106 USA. EM jpark@abim.org FU Agency for Healthcare Research and Quality [R01 HS016478-01]; VA HSRD FX This research was funded by a grant from the Agency for Healthcare Research and Quality (R01 HS016478-01). Rachel M. Werner is supported in part by a VA HSR&D Career Development Award. We are grateful to Sally Stearns, Daniel Polsky, and Ryan Mutter for their helpful comments on an earlier draft of this manuscript. NR 39 TC 6 Z9 7 U1 1 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9230 J9 HEALTH ECON JI Health Econ. PD JUL PY 2011 VL 20 IS 7 BP 783 EP 801 DI 10.1002/hec.1632 PG 19 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 748HB UT WOS:000289379800003 PM 20578255 ER PT J AU Yuan, CM Wang, Z Inslicht, SS McCaslin, SE Metzler, TJ Henn-Haase, C Apfel, BA Tong, HQ Neylan, TC Fang, YR Marmar, CR AF Yuan, Chengmei Wang, Zhen Inslicht, Sabra S. McCaslin, Shannon E. Metzler, Thomas J. Henn-Haase, Clare Apfel, Brigitte A. Tong, Huiqi Neylan, Thomas C. Fang, Yiru Marmar, Charles R. TI Protective factors for posttraumatic stress disorder symptoms in a prospective study of police officers SO PSYCHIATRY RESEARCH LA English DT Article DE PTSD; Critical incident; World assumption; Social adjustment; Social support; Personality ID PSYCHOLOGICAL RESILIENCE; PERSONALITY-TRAITS; SOCIAL SUPPORT; MENTAL-HEALTH; RISK-FACTORS; WORLD ASSUMPTIONS; TRAUMA EXPOSURE; PTSD SYMPTOMS; PREDICTORS; ADULTS AB Although police officers are frequently exposed to potentially traumatic incidents. only a minority will develop chronic posttraumatic stress disorder (FTSD). Identifying and understanding protective factors could inform the development of preventive interventions; however, few studies have examined this. In the present prospective study, 233 police officers were assessed during academy training and again following 2 years of police service. Caucasian race, less previous trauma exposure, and less critical incident exposure during police service as well as greater sense of self-worth, beliefs of greater benevolence of the world, greater social support and better social adjustment, all assessed during academy training, were associated with lower PTSD symptoms after 2 years of service. Positive personality attributes assessed during training with the NEO Five-Factor Personality Inventory were not associated with lower PTSD symptoms. In a hierarchical linear regression model, only Caucasian race, lower critical incident exposure during police service, greater assumptions of benevolence of the world and better social adjustment during training remained predictive of lower PTSD symptoms after 2 years of police service. These results suggest that positive world assumptions and better social functioning during training may protect police officers from critical incident related PTSD. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Yuan, Chengmei; Fang, Yiru] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Div Mood Disorder, Shanghai 200030, Peoples R China. [Yuan, Chengmei; Wang, Zhen; Inslicht, Sabra S.; McCaslin, Shannon E.; Metzler, Thomas J.; Apfel, Brigitte A.; Tong, Huiqi; Neylan, Thomas C.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Yuan, Chengmei; Wang, Zhen; Inslicht, Sabra S.; McCaslin, Shannon E.; Apfel, Brigitte A.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Henn-Haase, Clare; Marmar, Charles R.] NYU, Dept Psychiat, New York, NY 10016 USA. [Wang, Zhen] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Dept Clin Psychol, Shanghai 200030, Peoples R China. RP Apfel, BA (reprint author), Vet Adm Med Ctr, Mental Hlth Serv, 4150 Clement St 116P, San Francisco, CA 94121 USA. EM brigitte.apfel@ucsf.edu; yirufang@yahoo.com.cn FU National Institute of Mental Health [5R01-MH056350-10] FX This research was supported by National Institute of Mental Health Grant No. 5R01-MH056350-10. NR 54 TC 13 Z9 14 U1 3 U2 36 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUN 30 PY 2011 VL 188 IS 1 BP 45 EP 50 DI 10.1016/j.psychres.2010.10.034 PG 6 WC Psychiatry SC Psychiatry GA 780DO UT WOS:000291834900009 PM 21095622 ER PT J AU Tinetti, ME Studenski, SA AF Tinetti, Mary E. Studenski, Stephanie A. TI Comparative Effectiveness Research and Patients with Multiple Chronic Conditions SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID OLDER PERSONS C1 [Tinetti, Mary E.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Tinetti, Mary E.] Yale Univ, Sch Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Studenski, Stephanie A.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Studenski, Stephanie A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Tinetti, ME (reprint author), Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. NR 5 TC 78 Z9 79 U1 1 U2 6 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 JUN 30 PY 2011 VL 364 IS 26 BP 2478 EP 2481 DI 10.1056/p1100535 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 785AM UT WOS:000292199800003 PM 21696327 ER PT J AU Lagergren, J Mattsson, F El-Serag, H Nordenstedt, H AF Lagergren, J. Mattsson, F. El-Serag, H. Nordenstedt, H. TI Increased risk of hepatocellular carcinoma after cholecystectomy SO BRITISH JOURNAL OF CANCER LA English DT Article DE liver cancer; gall bladder; epidemiology; risk ID CANCER; LIVER AB BACKGROUND: The association between gall bladder removal (cholecystectomy) and hepatocellular carcinoma warrants investigation. An increased intrahepatic bile duct pressure following cholecystectomy might cause chronic inflammation in the surrounding liver tissue, which might induce cancer development. METHODS: A nationwide Swedish population-based cohort study in 1965-2008 included 345 251 patients undergoing cholecystectomy because of gallstone. The number of observed hepatocellular carcinoma cases was divided by the expected number, calculated from the corresponding background Swedish population, thus providing standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). RESULTS: During follow-up of 4 854 969 person-years, 333 new cases of hepatocellular carcinoma were identified, rendering an overall increased risk (SIR 1.24, 95% CI: 1.11-1.38). The risk increased with longer follow-up (P for trend = 0.003). Among patients who underwent cholecystectomy 30-43 years earlier, SIR was 2.00 (95% CI: 1.32-2.87). The results were similar after exclusion of 15 634 patients with any recorded risk factor, that is, diabetes, obesity, hepatitis, liver cirrhosis, alcoholism, or blood transfusion. CONCLUSION: Cholecystectomy might be associated with a long-term increased risk of hepatocellular carcinoma. British Journal of Cancer (2011) 105, 154-156. doi:10.1038/bjc.2011.181 www.bjcancer.com Published online 24 May 2011 (C) 2011 Cancer Research UK C1 [Lagergren, J.; Mattsson, F.; Nordenstedt, H.] Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden. [Lagergren, J.] Kings Coll London, London WC2R 2LS, England. [El-Serag, H.] Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. [El-Serag, H.] Michael E DeBakey Vet Adm Med Ctr, Houston, TX 77030 USA. RP Lagergren, J (reprint author), Karolinska Inst, Dept Mol Med & Surg, Norra Stationsgatan 67,Level 2, S-17176 Stockholm, Sweden. EM Jesper.Lagergren@ki.se OI Lagergren, Jesper/0000-0002-5143-5448 FU Swedish Research Council (SIMSAM); Swedish Cancer Society FX This study was supported by project grants from the Swedish Research Council (SIMSAM) and the Swedish Cancer Society. NR 10 TC 9 Z9 11 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN 28 PY 2011 VL 105 IS 1 BP 154 EP 156 DI 10.1038/bjc.2011.181 PG 3 WC Oncology SC Oncology GA 784TZ UT WOS:000292182400023 PM 21610710 ER PT J AU Win, AK Dowty, JG English, DR Campbell, PT Young, JP Winship, I Macrae, FA Lipton, L Parry, S Young, GP Buchanan, DD Martinez, ME Jacobs, ET Ahnen, DJ Haile, RW Casey, G Baron, JA Lindor, NM Thibodeau, SN Newcomb, PA Potter, JD Le Marchand, L Gallinger, S Hopper, JL Jenkins, MA AF Win, A. K. Dowty, J. G. English, D. R. Campbell, P. T. Young, J. P. Winship, I. Macrae, F. A. Lipton, L. Parry, S. Young, G. P. Buchanan, D. D. Martinez, M. E. Jacobs, E. T. Ahnen, D. J. Haile, R. W. Casey, G. Baron, J. A. Lindor, N. M. Thibodeau, S. N. Newcomb, P. A. Potter, J. D. Le Marchand, L. Gallinger, S. Hopper, J. L. Jenkins, M. A. TI Body mass index in early adulthood and colorectal cancer risk for carriers and non-carriers of germline mutations in DNA mismatch repair genes SO BRITISH JOURNAL OF CANCER LA English DT Article DE body mass index; colorectal cancer; mismatch repair gene ID LYNCH-SYNDROME; COLON-CANCER; MICROSATELLITE INSTABILITY; FAMILY REGISTRY; BREAST-CANCER; OBESITY; METAANALYSIS; WEIGHT; COHORT; MEN AB BACKGROUND: Carriers of germline mutations in DNA mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC), but the modifiers of this risk are not well established. We estimated an association between body mass index (BMI) in early adulthood and subsequent risk of CRC for carriers and, as a comparison, estimated the association for non-carriers. METHODS: A weighted Cox regression was used to analyse height and weight at 20 years reported by 1324 carriers of MMR gene mutations (500 MLH1, 648 MSH2, 117 MSH6 and 59 PMS2) and 1219 non-carriers from the Colon Cancer Family Registry. RESULTS: During 122 304 person-years of observation, we observed diagnoses of CRC for 659 carriers (50%) and 36 non-carriers (3%). For carriers, the risk of CRC increased by 30% for each 5 kgm(-2) increment in BMI in early adulthood (hazard ratio, HR: 1.30; 95% confidence interval, CI: 1.08-1.58; P = 0.01), and increased by 64% for non-carriers (HR: 1.64; 95% CI: 1.02-2.64; P = 0.04) after adjusting for sex, country, cigarette smoking and alcohol drinking (and the MMR gene that was mutated in carriers). The difference in HRs for carriers and non-carriers was not statistically significant (P = 0.50). For MLH1 and PMS2 (MutL alpha heterodimer) mutation carriers combined, the corresponding increase was 36% (HR: 1.36; 95% CI: 1.05-1.76; P = 0.02). For MSH2 and MSH6 (MutS alpha heterodimer) mutation carriers combined, the HR was 1.26 (95% CI: 0.96-1.65; P = 0.09). There was no significant difference between the HRs for MutLa and MutSa heterodimer carriers (P = 0.56). CONCLUSION: Body mass index in early adulthood is positively associated with risk of CRC for MMR gene mutation carriers and non-carriers. British Journal of Cancer (2011) 105, 162-169. doi:10.1038/bjc.2011.172 www.bjcancer.com Published online 10 May 2011 (C) 2011 Cancer Research UK C1 [Win, A. K.; Dowty, J. G.; English, D. R.; Hopper, J. L.; Jenkins, M. A.] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3010, Australia. [English, D. R.] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia. [Campbell, P. T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Campbell, P. T.; Newcomb, P. A.; Potter, J. D.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Young, J. P.; Buchanan, D. D.] Queensland Inst Med Res, Familial Canc Lab, Herston, Qld 4006, Australia. [Winship, I.] Univ Melbourne, Parkville, Vic 3052, Australia. [Macrae, F. A.] Royal Melbourne Hosp, Dept Colorectal Med & Genet, Parkville, Vic 3050, Australia. [Lipton, L.] Royal Melbourne Hosp, Ludwig Inst Canc Res, Parkville, Vic 3050, Australia. [Parry, S.] Auckland City Hosp, New Zealand Familial Gastrointestinal Canc Regist, Auckland, New Zealand. [Parry, S.] Middlemore Hosp, Dept Gastroenterol, Auckland 6, New Zealand. [Young, G. P.] Flinders Univ S Australia, Flinders Ctr Canc Prevent & Control, Adelaide, SA 5001, Australia. [Martinez, M. E.; Jacobs, E. T.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. [Martinez, M. E.; Jacobs, E. T.] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA. [Ahnen, D. J.] Univ Colorado, Denver Sch Med, Denver, CO 80202 USA. [Ahnen, D. J.] Denver VA Med Ctr, Denver, CO USA. [Haile, R. W.; Casey, G.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Baron, J. A.] Dartmouth Med Sch, Dept Med, Lebanon, NH USA. [Baron, J. A.] Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH USA. [Lindor, N. M.; Thibodeau, S. N.] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Le Marchand, L.] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. [Gallinger, S.] Canc Care Ontario, Toronto, ON, Canada. RP Jenkins, MA (reprint author), Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Level 3,207 Bouverie St, Parkville, Vic 3010, Australia. EM m.jenkins@unimelb.edu.au RI Gallinger, Steven/E-4575-2013; Jenkins, Mark/P-7803-2015 OI Jenkins, Mark/0000-0002-8964-6160; Potter, John/0000-0001-5439-1500; Dowty, James/0000-0003-2383-0886; Win, Aung Ko/0000-0002-2794-5261; English, Dallas/0000-0001-7828-8188; Buchanan, Daniel/0000-0003-2225-6675; Winship, Ingrid/0000-0001-8535-6003 FU National Cancer Institute, National Institutes of Health [CA-95-011]; NHMRC Australia [ID 400160] FX This work was supported by the National Cancer Institute, National Institutes of Health under RFA #CA-95-011 and through cooperative agreements with members of the Colon CFR and Principal Investigators. Collaborating centres include Australasian Colorectal Cancer Family Registry (U01 CA097735), the USC Familial Colorectal Neoplasia Collaborative Group (U01 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), Seattle Colorectal Cancer Family Registry (U01 CA074794) and University of Hawaii Colorectal Cancer Family Registry (U01 CA074806). This work was also supported by a grant from NHMRC Australia (ID 400160). The content of this manuscript neither necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the CFRs, nor does mention of trade names, commercial products or organisations implies endorsement by the US Government or the CFR. We had full responsibility for the design of the study, the collection of the data, the analysis and interpretation of the data, the decision to submit the manuscript for publication and the writing of the manuscript. We thank Dr Elizabeth Williamson from Murdoch Childrens Research Institute, Melbourne, Australia for statistical advice. We thank all study participants of the Colon Cancer Family Registry and staff for their contributions to this project. NR 56 TC 15 Z9 16 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN 28 PY 2011 VL 105 IS 1 BP 162 EP 169 DI 10.1038/bjc.2011.172 PG 8 WC Oncology SC Oncology GA 784TZ UT WOS:000292182400025 PM 21559014 ER PT J AU Gibson, R Grady, D AF Gibson, Rosemary Grady, Deborah TI Patient Experience of Overtreatment SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Gibson, Rosemary] Robert Wood Johnson Fdn, Princeton, NJ USA. [Grady, Deborah] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Grady, Deborah] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. RP Gibson, R (reprint author), Robert Wood Johnson Fdn, Princeton, NJ USA. EM rosemarygibson100@gmail.com NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 27 PY 2011 VL 171 IS 12 BP 1054 EP 1054 DI 10.1001/archinternmed.2011.114 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 783WI UT WOS:000292114400001 PM 21444832 ER PT J AU Kullgren, JT Lieu, TA AF Kullgren, Jeffrey T. Lieu, Tracy A. TI More Health Care Is Not Necessarily Better Health Care Reply SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 [Kullgren, Jeffrey T.] Univ Penn, Robert Wood Johnson Fdn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Lieu, Tracy A.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Lieu, Tracy A.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. RP Kullgren, JT (reprint author), Univ Penn, Robert Wood Johnson Fdn, Philadelphia VA Med Ctr, 1303B Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM kullgren@mail.med.upenn.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 27 PY 2011 VL 171 IS 12 BP 1124 EP 1124 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 783WI UT WOS:000292114400023 ER PT J AU Hwang, U Morrison, RS Richardson, LD Todd, KH AF Hwang, Ula Morrison, R. Sean Richardson, Lynne D. Todd, Knox H. TI A Painful Setback: Misinterpretation of Analgesic Safety in Older Adults May Inadvertently Worsen Pain Care SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 [Hwang, Ula; Richardson, Lynne D.] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Hwang, Ula; Morrison, R. Sean] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Richardson, Lynne D.] Mt Sinai Sch Med, Dept Hlth Evidence & Policy, New York, NY 10029 USA. [Morrison, R. Sean] James J PetersVA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Todd, Knox H.] Univ Texas MD Anderson Canc Ctr, Dept Emergency Med, Houston, TX 77030 USA. RP Hwang, U (reprint author), Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. EM ula.hwang@mountsinai.org FU NIA NIH HHS [K24 AG022345, K23 AG31218, K23 AG031218, K24 AG22345] NR 10 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 27 PY 2011 VL 171 IS 12 BP 1127 EP 1127 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 783WI UT WOS:000292114400028 PM 21709124 ER PT J AU Vaid, M Singh, T Katiyar, SK AF Vaid, Mudit Singh, Tripti Katiyar, Santosh K. TI Grape Seed Proanthocyanidins Inhibit Melanoma Cell Invasiveness by Reduction of PGE(2) Synthesis and Reversal of Epithelial-to-Mesenchymal Transition SO PLOS ONE LA English DT Article ID NF-KAPPA-B; LUNG-CANCER; MOUSE SKIN; INFLAMMATORY RESPONSES; GUANYLATE-CYCLASE; PROSTAGLANDIN E-2; CARCINOMA-CELLS; NITRIC-OXIDE; CYCLOOXYGENASE-2; MIGRATION AB Melanoma is the leading cause of death from skin disease due, in large part, to its propensity to metastasize. We have examined the effect of grape seed proanthocyanidins (GSPs) on melanoma cancer cell migration and the molecular mechanisms underlying these effects using highly metastasis-specific human melanoma cell lines, A375 and Hs294t. Using in vitro cell invasion assays, we observed that treatment of A375 and Hs294t cells with GSPs resulted in a concentration-dependent inhibition of invasion or cell migration of these cells, which was associated with a reduction in the levels of cyclooxygenase (COX)-2 expression and prostaglandin (PG) E-2 production. Treatment of cells with celecoxib, a COX-2 inhibitor, or transient transfection of melanoma cells with COX-2 small interfering RNA, also inhibited melanoma cell migration. Treatment of cells with 12-O-tetradecanoylphorbol-13-acetate, an inducer of COX-2, enhanced the phosphorylation of ERK1/2, a protein of mitogen-activated protein kinase family, and subsequently cell migration whereas both GSPs and celecoxib significantly inhibited 12-O-tetradecanoylphorbol-13-acetate - promoted cell migration as well as phosphorylation of ERK1/2. Treatment of cells with UO126, an inhibitor of MEK, also inhibited the migration of melanoma cells. Further, GSPs inhibited the activation of NF-kappa B/p65, an upstream regulator of COX-2, in melanoma cells, and treatment of cells with caffeic acid phenethyl ester, an inhibitor of NF-kappa B, also inhibited cell migration. Additionally, inhibition of melanoma cell migration by GSPs was associated with reversal of epithelial-mesenchymal transition process, which resulted in an increase in the levels of epithelial biomarkers (E-cadherin and cytokeratins) while loss of mesenchymal biomarkers (vimentin, fibronectin and N-cadherin) in melanoma cells. Together, these results indicate that GSPs have the ability to inhibit melanoma cell invasion/migration by targeting the endogenous expression of COX-2 and reversing the process of epithelial-to-mesenchymal transition. C1 [Vaid, Mudit; Singh, Tripti; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Vaid, M (reprint author), Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU Veterans Administration FX This work was supported by funds from the Veterans Administration Merit Review Award (SKK). There is no grant number. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 29 Z9 30 U1 3 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 JUN 27 PY 2011 VL 6 IS 6 AR e21539 DI 10.1371/journal.pone.0021539 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 783OD UT WOS:000292092600051 PM 21738696 ER PT J AU Reese, PP Feldman, HI Bloom, RD Abt, PL Thomasson, A Shults, J Grossman, R Asch, DA AF Reese, Peter P. Feldman, Harold I. Bloom, Roy D. Abt, Peter L. Thomasson, Arwin Shults, Justine Grossman, Robert Asch, David A. TI Assessment of Variation in Live Donor Kidney Transplantation Across Transplant Centers in the United States SO TRANSPLANTATION LA English DT Article DE Live donor transplantation; Health services research; Center variation ID INTRAVENOUS IMMUNE GLOBULIN; RENAL-TRANSPLANTATION; RACIAL DISPARITIES; DONATION; RECIPIENTS; CANDIDATES; OUTCOMES; PROGRAM; BLACK; RISK AB Background. Transplant centers vary in the proportion of kidney transplants performed using live donors. Clinical innovations that facilitate live donation may drive this variation. Methods. We assembled a cohort of renal transplant candidates at 194 US centers using registry data from 1999 to 2005. We measured magnitude of live donor kidney transplantation (LDKTx) through development of a standardized live donor transplantation ratio (SLDTR) at each center that accounted for center population differences. We examined associations between center characteristics and the likelihood that individual transplant candidates underwent LDKTx. To identify practices through which centers increase LDKTx, we also examined center characteristics associated with consistently being in the upper three quartiles of SLDTR. Results. The cohort comprised 148,168 patients, among whom 34,593 (23.3%) underwent LDKTx. In multivariable logistic regression, candidates had an increased likelihood of undergoing LDKTx at centers with greater use of "unrelated donors" (defined as nonspouses and nonfirst-degree family members of the recipient; odds ratio [OR] 1.31 for highest vs. lowest use; P=0.02) and at centers with programs to overcome donor-recipient incompatibility (OR 1.33; P=0.01). Centers consistently in the upper three SLDTR quartiles were also more likely to use "unrelated" donors (OR 8.30 per tertile of higher use; P<0.01), to have incompatibility programs (OR 4.79, P<0.01), and to use laparoscopic nephrectomy (OR 2.53 per tertile of higher use; P=0.02). Conclusion. Differences in center population do not fully account for differences in the use of LDKTx. To maximize opportunities for LDKTx, centers may accept more unrelated donors and adopt programs to overcome biological incompatibility. C1 [Reese, Peter P.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Reese, Peter P.; Feldman, Harold I.; Bloom, Roy D.; Grossman, Robert] Univ Penn, Dept Med, Div Renal, Philadelphia, PA 19104 USA. [Reese, Peter P.; Feldman, Harold I.; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Abt, Peter L.] Univ Penn, Transplant Inst, Dept Surg, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP Reese, PP (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 917 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM peter.reese@uphs.upenn.edu OI Asch, David/0000-0002-7970-286X FU Health Resources and Services Administration [234 2005 370011C]; NIH [K23 DK078688-01, K24-DK002651] FX This work was supported in part by Health Resources and Services Administration contract 234 2005 370011C, by NIH Career Development Award K23 DK078688-01 (P. P. R.), and by NIH grant K24-DK002651 (H.I.F.). NR 38 TC 8 Z9 8 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 27 PY 2011 VL 91 IS 12 BP 1357 EP 1363 DI 10.1097/TP.0b013e31821bf138 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 775BE UT WOS:000291430500011 PM 21562451 ER PT J AU Pena, A AF Pena, Adolfo TI Philosophy, medicine and clinical reasoning. Part II SO MEDICINA CLINICA LA Spanish DT Editorial Material ID VISUAL WORKING-MEMORY; FLUID INTELLIGENCE; MODEL; CATEGORIZATION; MECHANISMS; WORKSPACE; EDUCATION; CAPACITY; SCRIPTS C1 Univ Alabama, Birmingham VA Med Ctr, UAB VAQS Qual Scholars Fellowship Program, Birmingham, AL 35294 USA. RP Pena, A (reprint author), Univ Alabama, Birmingham VA Med Ctr, UAB VAQS Qual Scholars Fellowship Program, Birmingham, AL 35294 USA. EM adolfope@uab.edu NR 44 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 0025-7753 J9 MED CLIN-BARCELONA JI Med. Clin. PD JUN 25 PY 2011 VL 137 IS 3 BP 131 EP 135 DI 10.1016/j.medcli.2009.10.049 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 779MR UT WOS:000291782500009 PM 20056259 ER PT J AU Zuo, XF Fogelgren, B Lipschutz, JH AF Zuo, Xiaofeng Fogelgren, Ben Lipschutz, Joshua H. TI The Small GTPase Cdc42 Is Necessary for Primary Ciliogenesis in Renal Tubular Epithelial Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; REGULATED KINASE PATHWAY; RAC1 SMALL GTPASES; RHO-GTPASES; SPINDLE ORIENTATION; AUTOSOMAL-DOMINANT; CYST FORMATION; PRIMARY CILIUM; IN-VITRO; EXOCYST AB Primary cilia are found on many epithelial cell types, including renal tubular epithelial cells, where they participate in flow sensing. Disruption of cilia function has been linked to the pathogenesis of polycystic kidney disease. We demonstrated previously that the exocyst, a highly conserved eight-protein membrane trafficking complex, localizes to primary cilia of renal tubular epithelial cells, is required for ciliogenesis, biochemically and genetically interacts with polycystin-2 (the protein product of the polycystic kidney disease 2 gene), and, when disrupted, results in MAPK pathway activation both in vitro and in vivo. The small GTPase Cdc42 is a candidate for regulation of the exocyst at the primary cilium. Here, we demonstrate that Cdc42 biochemically interacts with Sec10, a crucial component of the exocyst complex, and that Cdc42 colocalizes with Sec10 at the primary cilium. Expression of dominant negative Cdc42 and shRNA-mediated knockdown of both Cdc42 and Tuba, a Cdc42 guanine nucleotide exchange factor, inhibit ciliogenesis in Madin-Darby canine kidney cells. Furthermore, exocyst Sec8 and polycystin-2 no longer localize to primary cilia or the ciliary region following Cdc42 and Tuba knockdown. We also show that Sec10 directly interacts with Par6, a member of the Par complex that itself directly interacts with Cdc42. Finally, we show that Cdc42 knockdown results in activation of the MAPK pathway, something observed in cells with dysfunctional primary cilia. These data support a model in which Cdc42 localizes the exocyst to the primary cilium, whereupon the exocyst then targets and docks vesicles carrying proteins necessary for ciliogenesis. C1 [Zuo, Xiaofeng; Fogelgren, Ben; Lipschutz, Joshua H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Lipschutz, Joshua H.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA 19104 USA. RP Lipschutz, JH (reprint author), 413 Hill Pavil,380 S Univ Ave, Philadelphia, PA 19104 USA. EM jhlipsch@mail.med.upenn.edu FU National Institutes of Health [DK069909, K01DK087852]; Veterans Affairs; Satellite Healthcare; University of Pennsylvania Translational Medicine Institute FX This work was supported, in whole or in part, by National Institutes of Health Grants DK069909 (to J. H. L.) and K01DK087852 (to B. F.). This work was also supported by a Veterans Affairs Merit Award (to J. H. L.), a Satellite Healthcare Norman S. Coplon extramural research grant (to J. H. L.), and a University of Pennsylvania Translational Medicine Institute pilot grant (to J. H. L). NR 41 TC 25 Z9 25 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 JUN 24 PY 2011 VL 286 IS 25 BP 22469 EP 22477 DI 10.1074/jbc.M111.238469 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 778QP UT WOS:000291719900055 PM 21543338 ER PT J AU Katiyar, SK Mantena, SK Meeran, SM AF Katiyar, Santosh K. Mantena, Sudheer K. Meeran, Syed M. TI Silymarin Protects Epidermal Keratinocytes from Ultraviolet Radiation-Induced Apoptosis and DNA Damage by Nucleotide Excision Repair Mechanism SO PLOS ONE LA English DT Article ID GREEN TEA POLYPHENOLS; A-DEPENDENT MECHANISM; INDUCED IMMUNOSUPPRESSION; SKIN-CANCER; ACTIVATION; PHOTOCARCINOGENESIS; INTERLEUKIN-12; ENHANCEMENT; CONTRIBUTE; CELLS AB Solar ultraviolet (UV) radiation is a well recognized epidemiologic risk factor for melanoma and non-melanoma skin cancers. This observation has been linked to the accumulation of UVB radiation-induced DNA lesions in cells, and that finally lead to the development of skin cancers. Earlier, we have shown that topical treatment of skin with silymarin, a plant flavanoid from milk thistle (Silybum marianum), inhibits photocarcinogenesis in mice; however it is less understood whether chemopreventive effect of silymarin is mediated through the repair of DNA lesions in skin cells and that protect the cells from apoptosis. Here, we show that treatment of normal human epidermal keratinocytes (NHEK) with silymarin blocks UVB-induced apoptosis of NHEK in vitro. Silymarin reduces the amount of UVB radiation-induced DNA damage as demonstrated by reduced amounts of cyclobutane pyrimidine dimers (CPDs) and as measured by comet assay, and that ultimately may lead to reduced apoptosis of NHEK. The reduction of UV radiation-induced DNA damage by silymarin appears to be related with induction of nucleotide excision repair (NER) genes, because UV radiation-induced apoptosis was not blocked by silymarin in NER-deficient human fibroblasts. Cytostaining and dot-blot analysis revealed that silymarin repaired UV-induced CPDs in NER-proficient fibroblasts from a healthy individual but did not repair UV-induced CPD-positive cells in NER-deficient fibroblasts from patients suffering from xeroderma pigmentosum complementation-A disease. Similarly, immunohistochemical analysis revealed that silymarin did not reduce the number of UVB-induced sunburn/apoptotic cells in the skin of NER-deficient mice, but reduced the number of sunburn cells in their wild-type counterparts. Together, these results suggest that silymarin exert the capacity to reduce UV radiation-induced DNA damage and, thus, prevent the harmful effects of UV radiation on the genomic stability of epidermal cells. C1 [Katiyar, Santosh K.; Mantena, Sudheer K.; Meeran, Syed M.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Nutr Obes Res Ctr, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Ctr Aging, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU National Cancer Institute [RO1 CA140197]; Veterans Administration Merit Review Award FX RO1 CA140197 by National Cancer Institute (http//www.cancer.gov) and the Veterans Administration Merit Review Award *SKK). The human keratinocytes were obtained from the UAB Skin Diseases Research Center (AR050948). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 32 Z9 33 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 JUN 22 PY 2011 VL 6 IS 6 AR e21410 DI 10.1371/journal.pone.0021410 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 782TF UT WOS:000292033700079 PM 21731736 ER PT J AU Yan, JQ Xu, YQ Zhu, CS Zhang, LM Wu, AM Yang, Y Xiong, ZJ Deng, C Huang, XF Yenari, MA Yang, YG Ying, WH Wang, Q AF Yan, Junqiang Xu, Yunqi Zhu, Cansheng Zhang, Limin Wu, Aimin Yang, Yu Xiong, Zhaojun Deng, Chao Huang, Xu-Feng Yenari, Midori A. Yang, Yuan-Guo Ying, Weihai Wang, Qing TI Simvastatin Prevents Dopaminergic Neurodegeneration in Experimental Parkinsonian Models: The Association with Anti-Inflammatory Responses SO PLOS ONE LA English DT Article ID NMDA RECEPTOR ANTAGONISTS; D-ASPARTATE RECEPTORS; ALZHEIMERS-DISEASE; GLUTAMATE RECEPTORS; PREFRONTAL CORTEX; CORTICAL-NEURONS; RAT-BRAIN; SYNAPTIC PLASTICITY; MESSENGER-RNA; BASAL GANGLIA AB Background: In addition to their original applications to lowering cholesterol, statins display multiple neuroprotective effects. N-methyl-D-aspartate (NMDA) receptors interact closely with the dopaminergic system and are strongly implicated in therapeutic paradigms of Parkinson's disease (PD). This study aims to investigate how simvastatin impacts on experimental parkinsonian models via regulating NMDA receptors. Methodology/Principal Findings: Regional changes in NMDA receptors in the rat brain and anxiolytic-like activity were examined after unilateral medial forebrain bundle lesion by 6-hydroxydopamine via a 3-week administration of simvastatin. NMDA receptor alterations in the post-mortem rat brain were detected by [(3)H]MK-801(Dizocilpine) binding autoradiography. 6-hydroxydopamine treated PC12 was applied to investigate the neuroprotection of simvastatin, the association with NMDA receptors, and the anti-inflammation. 6-hydroxydopamine induced anxiety and the downregulation of NMDA receptors in the hippocampus, CA1(Cornu Ammonis 1 Area), amygdala and caudate putamen was observed in 6-OHDA(6-hydroxydopamine) lesioned rats whereas simvastatin significantly ameliorated the anxiety-like activity and restored the expression of NMDA receptors in examined brain regions. Significant positive correlations were identified between anxiolytic-like activity and the restoration of expression of NMDA receptors in the hippocampus, amygdala and CA1 following simvastatin administration. Simvastatin exerted neuroprotection in 6-hydroxydopamine-lesioned rat brain and 6-hydroxydopamine treated PC12, partially by regulating NMDA receptors, MMP9 (matrix metalloproteinase-9), and TNF-a (tumour necrosis factor-alpha). Conclusions/Significance: Our results provide strong evidence that NMDA receptor modulation after simvastatin treatment could partially explain its anxiolytic-like activity and anti-inflammatory mechanisms in experimental parkinsonian models. These findings contribute to a better understanding of the critical roles of simvastatin in treating PD via NMDA receptors. C1 [Yan, Junqiang; Xu, Yunqi; Zhu, Cansheng; Zhang, Limin; Wu, Aimin; Yang, Yu; Wang, Qing] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Neurol, Guangzhou 510275, Guangdong, Peoples R China. [Deng, Chao; Huang, Xu-Feng; Wang, Qing] Univ Wollongong, Sch Hlth Sci, Ctr Translat Neurosci, Wollongong, NSW 2522, Australia. [Xiong, Zhaojun] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Cardiol, Guangzhou 510275, Guangdong, Peoples R China. [Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Yang, Yuan-Guo; Ying, Weihai] Shanghai Jiao Tong Univ, Med X Res Inst, Shanghai 200030, Peoples R China. RP Yan, JQ (reprint author), Sun Yat Sen Univ, Affiliated Hosp 3, Dept Neurol, Guangzhou 510275, Guangdong, Peoples R China. EM denniswq@yahoo.com RI Huang, Xu-Feng/D-6053-2013; Huang, Xu-Feng/H-7408-2015; Deng, Chao/F-4417-2016 OI Huang, Xu-Feng/0000-0002-5895-2253; Deng, Chao/0000-0003-1147-5741 FU Third Affiliated Hospital of Sun Yat-Sen University; Fundamental Research Funds for the Central Universities [A77, 10ykzd08]; Program for New Century Excellent Talents in University (NCET2010, P.R. China); National Natural Science Foundation of China [81071031]; Australia National Health and Medical Research Council [NHMRC 514640] FX This work was supported by the Grant-In-Aid from the Third Affiliated Hospital of Sun Yat-Sen University, Fundamental Research Funds for the Central Universities (Grant No. A77 and 10ykzd08), Program for New Century Excellent Talents in University (NCET2010, P.R. China), National Natural Science Foundation of China (81071031), and Australia National Health and Medical Research Council Grant (NHMRC 514640) to Q.W. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 59 TC 38 Z9 41 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 JUN 22 PY 2011 VL 6 IS 6 AR e20945 DI 10.1371/journal.pone.0020945 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 782TF UT WOS:000292033700020 PM 21731633 ER PT J AU Kansagara, D Shekelle, P Qaseem, A AF Kansagara, Devan Shekelle, Paul Qaseem, Amir TI Intensive Insulin Therapy in Hospitalized Patients RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID CRITICALLY-ILL PATIENTS C1 [Kansagara, Devan] Portland VA Med Ctr, Portland, OR 97239 USA. [Shekelle, Paul] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA 19106 USA. RP Kansagara, D (reprint author), Portland VA Med Ctr, Portland, OR 97239 USA. NR 8 TC 0 Z9 0 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 21 PY 2011 VL 154 IS 12 BP 847 EP 848 DI 10.7326/0003-4819-154-12-201106210-00022 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 779SA UT WOS:000291800500028 ER PT J AU Choi, AI Vittinghoff, E Deeks, SG Weekley, CC Li, YM Shlipak, MG AF Choi, Andy I. Vittinghoff, Eric Deeks, Steven G. Weekley, Cristin C. Li, Yongmei Shlipak, Michael G. TI Cardiovascular risks associated with abacavir and tenofovir exposure in HIV-infected persons SO AIDS LA English DT Article DE antiretroviral therapy; cardiovascular disease; heart failure; HIV ID CHRONIC KIDNEY-DISEASE; COMBINATION ANTIRETROVIRAL THERAPY; REVERSE-TRANSCRIPTASE INHIBITORS; OF-VETERANS-AFFAIRS; MYOCARDIAL-INFARCTION; RENAL-FUNCTION; NAIVE PATIENTS; YOUNG-ADULTS; COHORT; RATES AB Objective: Abacavir use has been associated with cardiovascular risk, but it is unknown whether this association may be partly explained by patients with kidney disease being preferentially treated with abacavir to avoid tenofovir. Our objective was to compare associations of abacavir and tenofovir with cardiovascular risks in HIV-infected veterans. Design: Cohort study of 10 931 HIV-infected patients initiating antiretroviral therapy in the Veterans Health Administration from 1997 to 2007, using proportional hazards survival regression. Methods: Primary predictors were exposure to abacavir or tenofovir within the past 6 months, compared with no exposure to these drugs, respectively. Outcomes were time to first atherosclerotic cardiovascular event, defined as coronary, cerebrovascular, or peripheral arterial disease; and time to incident heart failure. Results: Over 60 588 person-years of observation, there were 501 cardiovascular and 194 heart failure events. Age-standardized event rates among abacavir and tenofovir users were 12.5 versus 8.2 per 1000 person-years for cardiovascular disease, and 3.9 and 3.7 per 1000 person-years for heart failure, respectively. In multivariate-adjusted models, including time-updated measurements of kidney function, recent abacavir use was significantly associated with incident cardiovascular disease [hazard ratio 1.48, 95% confidence interval (CI) 1.08-2.04]; the association was similar but nonsignificant for heart failure (1.45, 0.85-2.47). In contrast, recent tenofovir use was significantly associated with heart failure (1.82, 1.02-3.24), but not with cardiovascular events (0.78, 0.52-1.16). Conclusion: Recent abacavir exposure was independently associated with increased risk for cardiovascular events. We also observed an association between recent tenofovir exposure and heart failure, which needs to be confirmed in future studies. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Choi, Andy I.; Weekley, Cristin C.; Li, Yongmei; Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Choi, Andy I.; Vittinghoff, Eric; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Deeks, Steven G.] San Francisco Gen Hosp, Posit Hlth Program, San Francisco, CA 94110 USA. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, Dept Med, Box 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu FU National Institutes of Health [K23DK080645-01A1, 1R03AG034871-01, K24AI069994, R01 DK066488-01]; National Center for Research Resources [KL2 RR024130]; American Heart Association; VA Public Health Strategic Healthcare Group; Merck; Bristol-Myers Squibb; Gilead; Roche Molecular Sciences FX This study was supported by the National Institutes of Health [K23DK080645-01A1 (AIC), 1R03AG034871-01 (AIC/MGS), K24AI069994, R01 DK066488-01 (MGS/AIC)], the National Center for Research Resources (KL2 RR024130), the American Heart Association Established Investigator Award (MGS), and the VA Public Health Strategic Healthcare Group. These funding sources had no involvement in the design or execution of this study.; S.G.D. receives research support from Merck, Bristol-Myers Squibb, Gilead, and Roche Molecular Sciences. NR 52 TC 77 Z9 77 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUN 19 PY 2011 VL 25 IS 10 BP 1289 EP 1298 DI 10.1097/QAD.0b013e328347fa16 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 775MI UT WOS:000291463200006 PM 21516027 ER PT J AU Goebel-Stengel, M Wang, LX Stengel, A Tache, Y AF Goebel-Stengel, Miriam Wang, Lixin Stengel, Andreas Tache, Yvette TI Localization of nesfatin-1 neurons in the mouse brain and functional implication SO BRAIN RESEARCH LA English DT Article DE Fos; Hypothalamus; Medulla; NUCB2; Gastric emptying; Water avoidance stress ID CORTICOTROPIN-RELEASING-FACTOR; MELANIN-CONCENTRATING HORMONE; EDINGER-WESTPHAL-NUCLEUS; PITUITARY-ADRENAL AXIS; WATER-AVOIDANCE STRESS; DORSAL MOTOR NUCLEUS; FOS EXPRESSION; RAT-BRAIN; PARAVENTRICULAR NUCLEUS; FOOD-INTAKE AB Nesfatin-1 reduces food intake when injected centrally in rodents. We recently described wide distribution of nucleobindin2 (NUCB2)/nesfatin-1 immunoreactivity in rat brain autonomic nuclei activated by various stressors. We used C57BL/6 mice to localize brain NUCB2/nesfatin-1 immunoreactivity and assessed activation of NUCB2/nesfatin 1 neurons after water avoidance stress (WAS). Gastric emptying of a non-nutrient liquid was also determined. NUCB2/nesfatin-1 immunoreactivity was detected in cortical areas including piriform, insular, cingulate and somatomotor cortices, the limbic system including amygdaloid nuclei, hippocampus and septum, the basal ganglia, bed nucleus of the stria terminalis, the thalamus including paraventricular and parafascicular nuclei, the hypothalamus including supraoptic, periventricular, paraventricular (PVN), arcuate nuclei and ventromedial and lateral hypothalamic areas. Intensely labeled NUCB2/nesfatin-1 neurons were detected in a previously undefined region which we named intermediate dorsomedial hypothalamus. In the brainstem, NUCB2/nesfatin-1 immunoreactivity was detected in the raphe nuclei, Edinger-Westphal nucleus, locus coeruleus (LC), lateral parabrachial nucleus, ventrolateral medulla (VLM) and dorsal vagal complex. WAS induced Fos expression in 35% of NUCB2/nesfatin-1-immunoreactive neurons in the PVN, 50% in the LC, 54% in the rostral raphe pallidus, 58% in the VLM, 39% in the middle part of the nucleus of the solitary tract (NTS) and 33% in the caudal NTS. Nesfatin-1 injected intracerebroventricularly significantly decreased gastric emptying. These data showed that NUCB2/nesfatin-1 immunoreactivity is distributed in mouse brain areas involved in the regulation of stress response and visceral functions activated by an acute psychological stressor suggesting that nesfatin-1 might play a role in the efferent component of the stress response. Published by Elsevier B.V. C1 [Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress,Digest Dis Div,Dept Med, Los Angeles, CA 90095 USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU Department of Veterans Affairs, NIHDK [33061]; [DK-41301] FX This work was supported by the VA Research Career Scientist Award, Department of Veterans Affairs, NIHDK 33061 (Y.T.) and Center grant DK-41301 (Animal Core, Y.T.). We are grateful to Ms. Honghui Liang for her excellent technical support and Ms. Eugenia Hu for reviewing the manuscript. NR 57 TC 56 Z9 61 U1 1 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 17 PY 2011 VL 1396 BP 20 EP 34 DI 10.1016/j.brainres.2011.04.031 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 788AD UT WOS:000292416900003 PM 21555116 ER PT J AU Helfand, M AF Helfand, Mark TI Medical Research for Hire The Political Economy of Pharmaceutical Clinical Trials SO SCIENCE LA English DT Book Review C1 [Helfand, Mark] Portland VA Med Ctr, Portland, OR 97239 USA. [Helfand, Mark] Oregon Hlth & Sci Univ, Ctr Biomed Informat Commun, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. RP Helfand, M (reprint author), Portland VA Med Ctr, Portland, OR 97239 USA. EM helfand@ohsu.edu NR 2 TC 0 Z9 0 U1 1 U2 1 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 JUN 17 PY 2011 VL 332 IS 6036 BP 1383 EP 1383 DI 10.1126/science.1198268 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 778FT UT WOS:000291689000023 ER PT J AU Gradmark, A Pomeroy, J Renstrom, F Steiginga, S Persson, M Wright, A Bluck, L Domellof, M Kahn, SE Mogren, I Franks, PW AF Gradmark, Anna Pomeroy, Jeremy Renstrom, Frida Steiginga, Susanne Persson, Margareta Wright, Antony Bluck, Les Domellof, Magnus Kahn, Steven E. Mogren, Ingrid Franks, Paul W. TI Physical activity, sedentary behaviors, and estimated insulin sensitivity and secretion in pregnant and non-pregnant women SO BMC PREGNANCY AND CHILDBIRTH LA English DT Article DE pregnancy; physical activity; sedentary time; beta?beta?-cell response; insulin sensitivity ID ENERGY-EXPENDITURE; LONGITUDINAL CHANGES; GLUCOSE-TOLERANCE; LABELED WATER; RESISTANCE; INTERVENTION; PREVENTION; HUMANS AB Background: Overweight and obesity during pregnancy raise the risk of gestational diabetes and birth complications. Lifestyle factors like physical activity may decrease these risks through beneficial effects on glucose homeostasis. Here we examined physical activity patterns and their relationships with measures of glucose homeostasis in late pregnancy compared to non-pregnant women. Methods: Normal weight and overweight women without diabetes (N = 108; aged 25-35 years) were studied; 35 were pregnant (in gestational weeks 28-32) and 73 were non-pregnant. Insulin sensitivity and beta-cell response were estimated from an oral glucose tolerance test. Physical activity was measured during 10-days of free-living using a combined heart rate sensor and accelerometer. Total (TEE), resting (REE), and physical activity (PAEE) energy expenditure were measured using doubly-labeled water and expired gas indirect calorimetry. Results: Total activity was associated with reduced first-phase insulin response in both pregnant (Regression r(2) = 0.11; Spearman r = -0.47; p = 0.007) and non-pregnant women (Regression r2 = 0.11 Spearman; r = -0.36; p = 0.002). Relative to non-pregnant women, pregnant women were estimated to have secreted 67% more insulin and had 10% lower fasting glucose than non-pregnant women. Pregnant women spent 13% more time sedentary, 71% less time in moderate-to-vigorous intensity activity, had 44% lower objectively measured total activity, and 12% lower PAEE than non-pregnant women. Correlations did not differ significantly for any comparison between physical activity subcomponents and measures of insulin sensitivity or secretion. Conclusions: Our findings suggest that physical activity conveys similar benefits on glucose homeostasis in pregnant and non-pregnant women, despite differences in subcomponents of physical activity. C1 [Gradmark, Anna; Pomeroy, Jeremy; Renstrom, Frida; Steiginga, Susanne; Franks, Paul W.] Umea Univ Hosp, Med Sect, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden. [Pomeroy, Jeremy] NIDDK, NIH, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. [Pomeroy, Jeremy; Renstrom, Frida; Franks, Paul W.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden. [Renstrom, Frida; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Steiginga, Susanne] Free Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Persson, Margareta] Umea Univ Hosp, Dept Clin Sci, S-90185 Umea, Sweden. [Persson, Margareta] Umea Univ Hosp, Dept Nursing, S-90185 Umea, Sweden. [Wright, Antony; Bluck, Les] MRC Human Nutr Res, Cambridge, England. [Domellof, Magnus] Umea Univ Hosp, Dept Pediat, S-90185 Umea, Sweden. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Mogren, Ingrid] Umea Univ Hosp, Dept Clin Sci Obstet & Gynecol, S-90185 Umea, Sweden. RP Franks, PW (reprint author), Umea Univ Hosp, Med Sect, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden. EM paul.franks@med.lu.se RI Domellof, Magnus/E-5307-2011 OI Domellof, Magnus/0000-0002-0726-7029; Steiginga, Susanne/0000-0002-7015-2259; Mogren, Ingrid/0000-0003-2985-1135; Franks, Paul/0000-0002-0520-7604; Kahn, Steven/0000-0001-7307-9002 FU Torsten & Ragnar Soderbergs Foundation (via LifeGene); Fredrik; Ingrid Thurings Foundation, Visare Norr; Vasterbotten regional health authority; United States Department of Veterans Affairs; Heart-Lung Foundation; Swedish Diabetes Association; Swedish Heart-Lung Foundation; Swedish Research Council; Novo Nordisk FX We thank the participants in this study and M. Holmgren for assistance in collecting data. The study was a preparatory project for the LifeGene Study http://www.lifegene.se and was funded by Torsten & Ragnar Soderbergs Foundation (via LifeGene), Fredrik and Ingrid Thurings Foundation, Visare Norr, and Vasterbotten regional health authority (all grants to PWF). SEK was supported by the United States Department of Veterans Affairs. FR was support by a post-doctoral stipend from the Heart-Lung Foundation. PWF was supported by grants from the Swedish Diabetes Association, the Swedish Heart-Lung Foundation, the Swedish Research Council, and Novo Nordisk. NR 24 TC 21 Z9 21 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2393 J9 BMC PREGNANCY CHILDB JI BMC Pregnancy Childbirth PD JUN 16 PY 2011 VL 11 AR 44 DI 10.1186/1471-2393-11-44 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 840VP UT WOS:000296469800001 PM 21679399 ER PT J AU Leventhal, JS Alsauskas, Z Snyder, A Gong, PF Wang, B D'Agati, V Ross, MJ AF Leventhal, Jeremy S. Alsauskas, Zygimantas Snyder, Alexandra Gong, Pengfei Wang, Bin D'Agati, Vivette Ross, Michael J. TI Renal HIV Expression Is Unaffected by Serum LPS Levels in an HIV Transgenic Mouse Model of LPS Induced Kidney Injury SO PLOS ONE LA English DT Article ID FACTOR-KAPPA-B; TUBULAR EPITHELIAL-CELLS; HOSPITALIZED-PATIENTS; INFECTED PATIENTS; GENE-EXPRESSION; VIRAL LOAD; FAILURE; ACTIVATION; NEPHROPATHY; TAT AB Acute kidney injury (AKI) is associated with increased rates of mortality. For unknown reasons, HIV infected individuals have a higher risk of AKI than uninfected persons. We tested our hypothesis that increased circulating LPS increases renal expression of HIV and that HIV transgenic (Tg26) mice have increased susceptibility to AKI. Tg26 mice harbor an HIV transgene encoding all HIV genes except gag and pol, and develop a phenotype analogous to HIVAN. Mice were used at 4-6 weeks of age before the onset of gross renal disease. Mice were injected i.p. with LPS or sterile saline. Renal function, tubular injury, cytokine expression, and HIV transcription were evaluated in Tg26 and wild type (WT) mice. LPS injection induced a median 60.1-fold increase in HIV expression in spleen but no change in kidney. There was no significant difference in renal function, cytokine expression, or tubular injury scores at baseline or 24 hours after LPS injection. HIV transcription was also analyzed in vitro using a human renal tubular epithelial cell (RTEC) line. HIV transcription increased minimally in human RTEC, by 1.47 fold, 48 hours after LPS exposure. We conclude that Tg26 mice do not increase HIV expression or have increased susceptibility to LPS induced AKI. The increased risk of AKI in HIV infected patients is not mediated via increased renal expression of HIV in the setting of sepsis. Moreover, renal regulation of HIV transcription is different to that in the spleen. C1 [Leventhal, Jeremy S.; Gong, Pengfei; Wang, Bin; Ross, Michael J.] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. [Leventhal, Jeremy S.] James J Peters Bronx VA Med Ctr, Div Nephrol, Bronx, NY USA. [Alsauskas, Zygimantas] Univ Louisville, Div Nephrol, Louisville, KY 40292 USA. [D'Agati, Vivette] Columbia Univ, Dept Pathol, Med Ctr, New York, NY USA. RP Leventhal, JS (reprint author), Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. EM jeremy.leventhal@mssm.edu FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK078510]; National Kidney Foundation FX This work was supported by a National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant R01 DK078510 (to PI MR) and by a National Kidney Foundation Fellowship Grant (to JL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 2 Z9 2 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 16 PY 2011 VL 6 IS 6 AR e20688 DI 10.1371/journal.pone.0020688 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 778UW UT WOS:000291734100014 PM 21698182 ER PT J AU Chinai, JM Taylor, AB Ryno, LM Hargreaves, ND Morris, CA Hart, PJ Urbach, AR AF Chinai, Jordan M. Taylor, Alexander B. Ryno, Lisa M. Hargreaves, Nicholas D. Morris, Christopher A. Hart, P. John Urbach, Adam R. TI Molecular Recognition of Insulin by a Synthetic Receptor SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID AQUEOUS-SOLUTION; SUPRAMOLECULAR CHEMISTRY; SELECTIVE RECOGNITION; ARTIFICIAL RECEPTORS; LIGAND-BINDING; AMINO-ACID; PROTEINS; PEPTIDE; HOST; IMMOBILIZATION AB The discovery of molecules that bind tightly and selectively to desired proteins continues to drive innovation at the interface of chemistry and biology. This paper describes the binding of human insulin by the synthetic receptor cucurbit[7]uril (Q7) in vitro. Isothermal titration calorimetry and fluorescence spectroscopy experiments show that Q7 binds to insulin with an equilibrium association constant of 1.5 x 10(6) M-1 and with 50-100-fold selectivity versus proteins that are much larger but lack an N-terminal aromatic residue, and with >1000-fold selectivity versus an insulin variant lacking the N-terminal phenylalanine (Phe) residue. The crystal structure of the Q7 center dot insulin complex shows that binding occurs at the N-terminal Phe residue and that the N-terminus unfolds to enable binding. These findings suggest that site-selective recognition is based on the properties inherent to a protein terminus, including the unique chemical epitope presented by the terminal residue and the greater freedom of the terminus to unfold, like the end of a ball of string, to accommodate binding. Insulin recognition was predicted accurately from studies on short peptides and exemplifies an approach to protein recognition by targeting the terminus. C1 [Chinai, Jordan M.; Ryno, Lisa M.; Hargreaves, Nicholas D.; Morris, Christopher A.; Urbach, Adam R.] Trinity Univ, Dept Chem, San Antonio, TX 78212 USA. [Taylor, Alexander B.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, S Texas Hlth Care Syst, Dept Biochem, San Antonio, TX 78229 USA. [Taylor, Alexander B.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, S Texas Hlth Care Syst, Xray Crystallog Core Lab, San Antonio, TX 78229 USA. [Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, S Texas Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Dept Vet Affairs, San Antonio, TX 78229 USA. RP Urbach, AR (reprint author), Trinity Univ, Dept Chem, 1 Trinity Pl, San Antonio, TX 78212 USA. EM aurbach@trinity.edu OI Dybdal-Hargreaves, Nicholas/0000-0002-5847-5231 FU National Science Foundation [CHE-0748483, DBI-0718766]; Welch Foundation [W-1640, AQ-1399]; W. M. Keck Foundation; Camille and Henry Dreyfus Foundation; National Center for Research Resources at the National Institutes of Health [RR-15301]; U.S. Department of Energy, Office of Basic Energy Sciences [DE-AC02-06CH11357]; Institutional Executive Research Council; San Antonio Cancer Institute FX This paper is dedicated to Prof. Jonathan L. Sessler on the occasion of his 55th birthday. Support for this work from the National Science Foundation (CHE-0748483, ARU) and Welch Foundation (W-1640, ARU and AQ-1399, PJH) is gratefully acknowledied. We thank Novo Nordisk for generous donation of the GluB1, GluB27 variant insulin 2. The circular dichroism spectropolarimeter was provided by a grant from the National Science Foundation (DBI-0718766, ARU). The fluorescence spectrometer and titration calorimeter were provided by a grant to Trinity University by the W. M. Keck Foundation. LMR had a Jean Dreyfus Boissevain Undergraduate Scholarship for Excellence in Chemistry from the Camille and Henry Dreyfus Foundation. This work is based on research conducted at the Advanced Photon Source on the Northeastern Collaborative Access Team (NE-CAT) beamlines, which are supported by award RR-15301 from the National Center for Research Resources at the National Institutes of Health. Use of the Advanced Photon Source is supported by the U.S. Department of Energy, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. We thank Dr. Jonathan P. Schuermann of NE-CAT for collecting the data for the Q7.1 complex. Support for the X-ray Crystallography Core Laboratory at the University of Texas Health Science Center by the Institutional Executive Research Council and the San Antonio Cancer Institute is gratefully acknowledged. NR 37 TC 105 Z9 105 U1 7 U2 75 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 15 PY 2011 VL 133 IS 23 BP 8810 EP 8813 DI 10.1021/ja201581x PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 777ZX UT WOS:000291667600010 PM 21473587 ER PT J AU Maciejewski, ML Livingston, EH Smith, VA Kavee, AL Kahwati, LC Henderson, WG Arterburn, DE AF Maciejewski, Matthew L. Livingston, Edward H. Smith, Valerie A. Kavee, Andrew L. Kahwati, Leila C. Henderson, William G. Arterburn, David E. TI Survival Among High-Risk Patients After Bariatric Surgery SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LONG-TERM MORTALITY; QUALITY IMPROVEMENT PROGRAM; TREATMENT SELECTION BIAS; AFFAIRS MEDICAL-CENTERS; GASTRIC BYPASS-SURGERY; VETERANS-AFFAIRS; PROPENSITY-SCORE; OBESITY; PERFORMANCE; PREVALENCE AB Context Existing evidence of the survival associated with bariatric surgery is based on cohort studies of predominantly younger women with a low inherent obesity-related mortality risk. The association of survival and bariatric surgery for older men is less clear. Objective To determine whether bariatric surgery is associated with reduced mortality in a multisite cohort of predominantly older male patients who have a high baseline mortality rate. Design, Setting, and Participants Retrospective cohort study of bariatric surgery programs in Veterans Affairs medical centers. Mortality was examined for 850 veterans who had bariatric surgery in January 2000 to December 2006 (mean age 49.5 years; SD 8.3; mean body mass index [BMI] 47.4; SD 7.8) and 41 244 nonsurgical controls (mean age 54.7 years, SD 10.2; mean BMI 42.0, SD 5.0) from the same 12 Veteran Integrated Service Networks; the mean follow-up was 6.7 years. Four Cox proportional hazards models were assessed: unadjusted and controlled for baseline covariates on unmatched and propensity-matched cohorts. Main Outcome Measure All-cause mortality through December 2008. Results Among patients who had bariatric surgery, the 1-, 2-, and 6-year crude mortality rates were, respectively, 1.5%, 2.2%, and 6.8% compared with 2.2%, 4.6%, and 15.2% for nonsurgical controls. In unadjusted Cox regression, bariatric surgery was associated with reduced mortality (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.51-0.80). After covariate adjustment, bariatric surgery remained associated with reduced mortality (HR, 0.80; 95% CI, 0.63-0.995). In analysis of 1694 propensity-matched patients, bariatric surgery was no longer significantly associated with reduced mortality in unadjusted (HR, 0.83; 95% CI, 0.61-1.14) and time-adjusted (HR, 0.94; 95% CI, 0.64-1.39) Cox regressions. Conclusion In propensity score-adjusted analyses of older severely obese patients with high baseline mortality in Veterans Affairs medical centers, the use of bariatric surgery compared with usual care was not associated with decreased mortality during a mean 6.7 years of follow-up. JAMA. 2011;305(23):2419-2426 www.jama.com C1 [Maciejewski, Matthew L.; Smith, Valerie A.; Kavee, Andrew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. [Maciejewski, Matthew L.] Duke Univ, Dept Med, Div Gen Internal Med, Durham, NC USA. [Livingston, Edward H.] Univ Texas SW Med Ctr Dallas, Div Gastrointestinal & Endocrine Surg, Dallas, TX 75390 USA. [Livingston, Edward H.] Vet Adm N Texas Hlth Care Syst, Dallas, TX USA. [Livingston, Edward H.] Univ Texas Arlington, Arlington, TX USA. [Kahwati, Leila C.] US Dept Vet Affairs, Natl Ctr Hlth Promot & Dis Prevent, Off Patient Care Serv, Durham, NC USA. [Henderson, William G.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Henderson, William G.] Univ Colorado, Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. [Henderson, William G.] Univ Colorado, Colorado Hlth Outcomes Program, Aurora, CO USA. [Arterburn, David E.] Grp Hlth Res Inst, Seattle, WA USA. [Arterburn, David E.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA. RP Maciejewski, ML (reprint author), Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care 152, 411 W Chapel Hill St,Ste 600, Durham, NC 27705 USA. EM matthew.maciejewski@va.gov FU Takeda Pharmaceuticals; Novartis; Surgical Review Corporation; Research Data and Assistance Center at the University of Minnesota; Texas Instruments; Foundation for Informed Medical Decision Making [501[3]c] FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Maciejewski reports receiving consultation funds from Takeda Pharmaceuticals, Novartis, the Surgical Review Corporation, and the Research Data and Assistance Center at the University of Minnesota and owns stock in Amgen. Dr Livingston reports receiving consulting funds from Texas Instruments. Dr Arterburn reports receiving research funding and has received salary support as a medical editor for the not-for-profit (501[3]c) Foundation for Informed Medical Decision Making (http://www.fimdm.org), which develops content for patient education programs. The foundation has an arrangement with a for-profit company, Health Dialog, to coproduce and market these programs to health care organizations. Dr Arterburn was formerly with the Cincinnati Veterans Affairs and Dr Livingston was formerly with the Dallas Veterans Affairs. No other disclosures were reported. NR 39 TC 86 Z9 87 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 15 PY 2011 VL 305 IS 23 BP 2419 EP 2426 DI 10.1001/jama.2011.817 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 777EB UT WOS:000291597300021 PM 21666276 ER PT J AU Bonello, GB Pham, MH Begum, K Sigala, J Sataranatarajan, K Mummidi, S AF Bonello, Gregory B. Pham, Minh-Hieu Begum, Kazi Sigala, Jose Sataranatarajan, Kavithalakshmi Mummidi, Srinivas TI An Evolutionarily Conserved TNF-alpha-Responsive Enhancer in the Far Upstream Region of Human CCL2 Locus Influences Its Gene Expression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BETA-GLOBIN LOCUS; NF-KAPPA-B; ACTIVE CHROMATIN HUB; CHEMOATTRACTANT PROTEIN-1 GENE; TRANSCRIPTION FACTOR-BINDING; TUMOR-NECROSIS-FACTOR; TH2 CYTOKINE LOCUS; IN-VIVO; REGULATORY REGIONS; SPATIAL-ORGANIZATION AB Comparative cross-species genomic analysis has served as a powerful tool to discover novel noncoding regulatory regions that influence gene expression in several cytokine loci. In this study, we have identified several evolutionarily conserved regions (ECRs) that are shared between human, rhesus monkey, dog, and horse and that are upstream of the promoter regions that have been previously shown to play a role in regulating CCL2 gene expression. Of these, an ECR that was similar to 16.5 kb (-16.5 ECR) upstream of its coding sequence contained a highly conserved NF-kappa B site. The region encompassing the -16.5 ECR conferred TNF-alpha responsiveness to homologous and heterologous promoters. In vivo footprinting demonstrated that specific nucleotide residues in the -16.5 ECR were protected or became hypersensitive after TNF-alpha treatment. The footprinted regions were found to bind NF-kappa B subunits in vitro and in vivo. Mutation/deletion of the conserved NF-kappa B binding site in the -16.5 ECR led to loss of TNF-alpha responsiveness. After TNF-alpha stimulation, the -16.5 ECR showed increased sensitivity to nuclease digestion and loss of histone signatures that are characteristic of a repressive chromatin. Chromosome conformation capture assays indicated that -16.5 ECR physically interacts with the CCL2 proximal promoter after TNF-alpha stimulation. Taken together, these results suggest that the -16.5 ECR may play a critical role in the regulation of CCL2. The Journal of Immunology, 2011, 186: 7025-7038. C1 [Bonello, Gregory B.; Pham, Minh-Hieu; Begum, Kazi; Sigala, Jose; Sataranatarajan, Kavithalakshmi; Mummidi, Srinivas] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Bonello, Gregory B.; Pham, Minh-Hieu; Begum, Kazi; Sigala, Jose; Mummidi, Srinivas] S Texas Vet Hlth Care Syst, Ctr Personalized Med, San Antonio, TX 78229 USA. RP Mummidi, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr,Mail Code 7881, San Antonio, TX 78229 USA. EM mummidi@uthscsa.edu RI Mummidi, Srinivas/C-1004-2008 OI Mummidi, Srinivas/0000-0002-4068-6380 FU Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development FX This work was supported by a Merit Review grant awarded by the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development (to S.M.). NR 79 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2011 VL 186 IS 12 BP 7025 EP 7038 DI 10.4049/jimmunol.0900643 PG 14 WC Immunology SC Immunology GA 773LV UT WOS:000291309700044 PM 21551367 ER PT J AU Dubielecka, PM Hwynn, N Sengun, C Lee, S Lomas-Francis, C Singer, C Fernandez, HH Walker, RH AF Dubielecka, Patrycja M. Hwynn, Nelson Sengun, Cenk Lee, Soohee Lomas-Francis, Christine Singer, Carlos Fernandez, Hubert H. Walker, Ruth H. TI Two McLeod patients with novel mutations in XK SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE McLeod syndrome; Neuroacanthocytosis; XK protein; Kell protein; Acanthocytosis; McLeod blood group; Kx erythrocyte antigen; Kell blood group antigens ID KELL BLOOD-GROUP; GROUP SYSTEM; MESSENGER-RNA; SPLICE SITES; MOUSE KELL; PHENOTYPE; PROTEINS; NEUROACANTHOCYTOSIS; ACANTHOCYTES; TRANSPORT AB McLeod syndrome (MIS) is a rare. X-linked, late-onset, disease involving hematological, brain, and neuromuscular systems, caused by mutations in XK that result in either defective XK or complete loss of XK protein. Acanthocytosis of erythrocytes is a typical feature. We report novel mutations in two patients who exhibited typical clinical characteristics of MIS. The coding and flanking intronic regions of XK were amplified by PCR, sequenced, and compared with the normal XK sequence. XK protein, and its complexed partner protein, Kell, were assessed by Western blot analysis. Patient 1 was found to have a single base insertion, 605insA at 175Ile creating a frame shift within the coding sequence of XK. Patient 2 had a single base substitution in the 3' splice sequence of intron 2 (IVS2-2a>g). In both cases mutations resulted in the absence of XK protein. (C) 2011 Elsevier B.V. All rights reserved. C1 [Hwynn, Nelson] Scripps Clin, Div Neurol, La Jolla, CA 92037 USA. [Dubielecka, Patrycja M.] New York Blood Ctr, Lindsley F Kimball Res Inst, Cell Signaling Lab, New York, NY 10065 USA. [Sengun, Cenk; Singer, Carlos] Univ Miami, Dept Neurol, Miami, FL 33136 USA. [Lomas-Francis, Christine] New York Blood Ctr, Lab Immunohematol, Long Isl City, NY 11101 USA. [Fernandez, Hubert H.] Cleveland Clin, Dept Neurol, Cleveland, OH 44195 USA. [Walker, Ruth H.] James J Peters VAMC, Dept Neurol, Movement Disorders Clin, Bronx, NY 10468 USA. [Walker, Ruth H.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. RP Hwynn, N (reprint author), Scripps Clin, Div Neurol, 10666 N Torrey Pines Blvd,MS 313, La Jolla, CA 92037 USA. EM hwynn.nelson@scrippshealth.org FU NHLBI NIH HHS [R01 HL075716-01] NR 30 TC 3 Z9 4 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JUN 15 PY 2011 VL 305 IS 1-2 BP 160 EP 164 DI 10.1016/j.jns.2011.02.028 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 773SN UT WOS:000291330800031 PM 21463873 ER PT J AU Mayhew, DL Hornberger, TA Lincoln, HC Bamman, MM AF Mayhew, David L. Hornberger, Troy A. Lincoln, Hannah C. Bamman, Marcas M. TI Eukaryotic initiation factor 2B epsilon induces cap-dependent translation and skeletal muscle hypertrophy SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID SIGNALING MOLECULE PHOSPHORYLATION; GUANINE-NUCLEOTIDE EXCHANGE; PROTEIN-SYNTHESIS; RESISTANCE EXERCISE; MYOFIBER HYPERTROPHY; CLUSTER-ANALYSIS; MAMMALIAN TARGET; MESSENGER-RNA; AMINO-ACIDS; YOUNG MEN AB The purpose of this study was to identify signalling components known to control mRNA translation initiation in skeletal muscle that are responsive to mechanical load and may be partly responsible for myofibre hypertrophy. To accomplish this, we first utilized a human cluster model in which skeletal muscle samples from subjects with widely divergent hypertrophic responses to resistance training were used for the identification of signalling proteins associated with the degree myofibre hypertrophy. We found that of 11 translational signalling molecules examined, the response of p(T421/S424)-p70S6K phosphorylation and total eukaryotic initiation factor 2B epsilon (eIF2B epsilon) protein abundance after a single bout of unaccustomed resistance exercise was associated with myofibre hypertrophy following 16 weeks of training. Follow up studies revealed that overexpression of eIF2B epsilon alone was sufficient to induce an 87% increase in cap-dependent translation in L6 myoblasts in vitro and 21% hypertrophy of myofibres in mouse skeletal muscle in vivo (P < 0.05). However, genetically altering p70S6K activity had no impact on eIF2B epsilon protein abundance in mouse skeletal muscle in vivo or multiple cell lines in vitro (P > 0.05), suggesting that the two phenomena were not directly related. These are the first data that mechanistically link eIF2B epsilon abundance to skeletal myofibre hypertrophy, and indicate that eIF2B epsilon abundance may at least partially underlie the widely divergent hypertrophic phenotypes in human skeletal muscle exposed to mechanical stimuli. C1 [Mayhew, David L.] Univ Alabama Birmingham, Med Scientist Training Program, Birmingham, AL 35294 USA. [Mayhew, David L.; Bamman, Marcas M.] Univ Alabama Birmingham, Dept Phys & Biophys, Birmingham, AL 35294 USA. [Mayhew, David L.; Bamman, Marcas M.] Birmingham VA Med Ctr, Geriatr Res Educ & Clin Ctr, Birmingham, AL 35233 USA. [Hornberger, Troy A.; Lincoln, Hannah C.] Univ Wisconsin, Dept Comparat Biosci, Madison, WI 53706 USA. RP Bamman, MM (reprint author), 966McCallum Bldg,1530 3rd Ave S, Birmingham, AL 35294 USA. EM mbamman@uab.edu OI Hornberger, Troy/0000-0002-2349-1899 FU NIH [AG017896, AG031623, AR057347] FX We would like to sincerely thank Shane Kelly (UAB) for technical assistance. This work was supported by NIH grants AG017896 to M. M. B., AG031623 to D. L. M., AR057347 to T. A. H. NR 56 TC 27 Z9 28 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUN 15 PY 2011 VL 589 IS 12 BP 3023 EP 3037 DI 10.1113/jphysiol.2010.202432 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 785CV UT WOS:000292205900014 PM 21486778 ER PT J AU Turkmen, K Martin, J Akcay, A Nguyen, Q Ravichandran, K Faubel, S Pacic, A Ljubanovic, D Edelstein, CL Jani, A AF Turkmen, Kultigin Martin, Jessica Akcay, Ali Quocan Nguyen Ravichandran, Kameswaran Faubel, Sarah Pacic, Arijana Ljubanovic, Danica Edelstein, Charles L. Jani, Alkesh TI Apoptosis and Autophagy in Cold Preservation Ischemia SO TRANSPLANTATION LA English DT Article DE Autophagy; Apoptosis; Cold preservation ischemia ID TUBULAR EPITHELIAL-CELLS; DELAYED GRAFT FUNCTION; ACUTE-RENAL-FAILURE; REPERFUSION INJURY; RISK-FACTORS; INHIBITION; KIDNEY; RAT; TRANSPLANTATION; MACROAUTOPHAGY AB Background. Prolonged cold ischemia (CI) is a risk factor for the development of delayed graft function that predicts reduced 5-year kidney transplant survival. CI results in caspase-3 activation, tubular injury, and apoptosis. Autophagy, a highly conserved pathway that permits recycling of nutrients within the cell during stress, is linked to apoptosis. We hypothesized that CI during kidney preservation would induce autophagy. We sought to determine apoptosis and autophagic flux in CI. Methods. Autophagic flux and apoptosis were examined in kidneys of wild-type and green fluorescent protein (GFP)-microtubule-associated protein1 light chain 3 (LC3) transgenic mice that were subjected to 48 hr of CI. Autophagic flux was determined by performing experiments with and without bafilomycin A1. Results. CI alone significantly increased the number of apoptotic cells/hpf, caspase-3/7 activity, and protein expression of autophagy markers LC3 II and autophagy-related protein 5. To determine the effect of inhibiting autophagic flux on apoptosis, kidneys of wild-type and GFP-LC3 transgenic mice were subjected to 48 hr of CI in the presence of lysosomal inhibitor bafilomycin A1. The combination of CI and bafilomycin A1 suppressed autophagic flux and significantly reduced the number of apoptotic cells/hpf, caspase-3/7 activity, LC3 II (both by immunoblot and in GFP-LC3 transgenic mice), and autophagy-related protein 5 protein expression. Conclusion. In summary, we have shown that autophagy and autophagic flux are reduced in cold ischemic kidneys treated with bafilomycin A1. Reduced autophagy and autophagic flux were associated with a significant reduction in apoptotic cell death, which may provide a therapeutic rationale for including bafilomycin A1 in University of Wisconsin solution during organ preservation. C1 [Turkmen, Kultigin; Martin, Jessica; Akcay, Ali; Quocan Nguyen; Ravichandran, Kameswaran; Faubel, Sarah; Edelstein, Charles L.] Univ Colorado, Denver, CO 80202 USA. [Pacic, Arijana; Ljubanovic, Danica] Univ Zagreb, Hosp Dubrava, Univ Zagreb SOM, Zagreb 41000, Croatia. [Jani, Alkesh] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Jani, A (reprint author), Univ Colorado Denver, Div Renal Dis & Hypertens, 12700 E 19th Ave,C281, Aurora, CO 80045 USA. EM Alkesh.jani@ucdenver.edu FU NIH [RO1DK056851, RO1-DK-074835]; Turkish Society of Nephrology; [KO8DK069512]; [R01HL095363] FX This work was supported by KO8DK069512 (A.J.), R01HL095363 (S.F.), and NIH grants RO1DK056851 and RO1-DK-074835 (C.L.E.), and Turkish Society of Nephrology (K.T.). NR 32 TC 16 Z9 17 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 15 PY 2011 VL 91 IS 11 BP 1192 EP 1197 DI 10.1097/TP.0b013e31821ab9c8 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 769JN UT WOS:000291008800009 PM 21577181 ER PT J AU Reese, PP Halpern, SD Asch, DA Bloom, R Nathan, H Hasz, R Roth, J Reitsma, W Krefski, L Goerlitz, F DeLauro, G Blumberg, E Weng, FL Caplan, A Thomasson, A Shults, J Feldman, HI AF Reese, Peter P. Halpern, Scott D. Asch, David A. Bloom, Roy Nathan, Howard Hasz, Richard Roth, Joseph Reitsma, William Krefski, Louis Goerlitz, Fred DeLauro, Gina Blumberg, Emily Weng, Francis L. Caplan, Arthur Thomasson, Arwin Shults, Justine Feldman, Harold I. TI Longer-Term Outcomes After Kidney Transplantation From Seronegative Deceased Donors at Increased Risk for Blood-Borne Viral Infection SO TRANSPLANTATION LA English DT Article DE Kidney transplantation; Viral transmission; Human immunodeficiency virus; High-risk donor ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; ACID TESTING NAT; LIVER-TRANSPLANTATION; INFORMING CANDIDATES; TRANSMISSION; SURVIVAL; RECIPIENTS AB Background. Transmission of human immunodeficiency virus and hepatitis C to transplant recipients has drawn attention of the use of allografts from seronegative donors at increased risk for blood-borne viral infection (DIRVI). Methods. We performed a cohort study of 7803 kidney transplant recipients whose kidneys were recovered through one of two organ procurement organizations from 1996 to 2007. Detailed organ procurement organization data on donor risk factors were linked to recipient data from the Organ Procurement and Transplantation Network. Results. Median recipient follow-up was 3.9 years. Three hundred sixty-eight (5%) patients received DIRVI kidneys, a third of which were procured from donors with a history of injection drug use or commercial sex work. Compared with standard criteria kidney recipients, DIRVI kidney recipients were more likely to be human immunodeficiency virus positive or black. In multivariable Cox regression, using DIRVI recipients as the reference, recipients of standard criteria donor kidneys had lower mortality (hazard ratio [HR] 0.71, P < 0.01) and no difference in death-censored allograft failure(HR 1.09, P = 0.62), whereas recipients of expanded criteria donor kidneys had no significant difference in mortality (HR 0.98, P = 0.83) but a higher allograft failure rate (HR 1.93, P < 0.01). High-quality data on posttransplant recipient viral testing were not available. Conclusions. DIRVI kidney recipients experienced higher mortality than standard criteria kidney recipients. This finding could be explained if sicker patients received DIRVI kidneys (i.e., residual confounding) or the less likely possibility of undetected transmission of viral infections. Given the limitations of registry data used in this analysis, prospective studies are needed to further elucidate these findings. C1 [Reese, Peter P.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Reese, Peter P.; Halpern, Scott D.; Asch, David A.; Caplan, Arthur; Feldman, Harold I.] Univ Penn, Leonard Davis Inst, Philadelphia, PA 19104 USA. [Reese, Peter P.; Bloom, Roy; Feldman, Harold I.] Hosp Univ Penn, Div Renal, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Halpern, Scott D.] Univ Penn, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Nathan, Howard; Hasz, Richard] Gift Life Inst, Philadelphia, PA USA. [Roth, Joseph; Reitsma, William; Krefski, Louis; Goerlitz, Fred; DeLauro, Gina] New Jersey Sharing Network, Springfield, NJ USA. [Blumberg, Emily] Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA. [Weng, Francis L.] St Barnabas Hosp, Livingston, NJ USA. [Halpern, Scott D.; Caplan, Arthur] Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. RP Reese, PP (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 908 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM peter.reese@uphs.upenn.edu OI Asch, David/0000-0002-7970-286X FU NIH [K23-DK078688-01, K24-DK002651]; Greenwall Foundation; Health Resources and Services Administration [234-2005-370011C] FX This work was supported by NIH Career Development Award, K23-DK078688-01 (P.P.R.), a Greenwall Foundation Faculty Scholar Award in Bioethics (S.D.H.), NIH grant K24-DK002651 (H.I.F.), and in part by Health Resources and Services Administration contract 234-2005-370011C. NR 19 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 15 PY 2011 VL 91 IS 11 BP 1211 EP 1217 DI 10.1097/TP.0b013e318218d59a PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 769JN UT WOS:000291008800012 PM 21527872 ER PT J AU Sudarshan, S Shanmugasundaram, K Naylor, SL Lin, S Livi, CB O'Neill, CF Parekh, DJ Yeh, IT Sun, LZ Block, K AF Sudarshan, Sunil Shanmugasundaram, Karthigayan Naylor, Susan L. Lin, Shu Livi, Carolina B. O'Neill, Christine F. Parekh, Dipen J. Yeh, I-Tien Sun, Lu-Zhe Block, Karen TI Reduced Expression of Fumarate Hydratase in Clear Cell Renal Cancer Mediates HIF-2 alpha Accumulation and Promotes Migration and Invasion SO PLOS ONE LA English DT Article ID HYPOXIA-INDUCIBLE FACTORS; TUMOR-SUPPRESSOR GENE; PROLYL HYDROXYLATION; HIF-ALPHA; CARCINOMA; MUTATIONS; PARAGANGLIOMA; PROTEIN; OVEREXPRESSION; SUSCEPTIBILITY AB Germline mutations of FH, the gene that encodes for the tricarboxylic acid TCA (TCA) cycle enzyme fumarate hydratase, are associated with an inherited form of cancer referred to as Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). Individuals with HLRCC are predisposed to the development of highly malignant and lethal renal cell carcinoma (RCC). The mechanisms of tumorigenesis proposed have largely focused on the biochemical consequences of loss of FH enzymatic activity. While loss of the tumor suppressor gene von Hippel Lindau (VHL) is thought to be an initiating event for the majority of RCCs, a role for FH in sporadic renal cancer has not been explored. Here we report that FH mRNA and protein expression are reduced in clear cell renal cancer, the most common histologic variant of kidney cancer. Moreover, we demonstrate that reduced FH leads to the accumulation of hypoxia inducible factor-2 alpha (HIF-2 alpha), a transcription factor known to promote renal carcinogenesis. Finally, we demonstrate that overexpression of FH in renal cancer cells inhibits cellular migration and invasion. These data provide novel insights into the tumor suppressor functions of FH in sporadic kidney cancer. C1 [Sudarshan, Sunil; Shanmugasundaram, Karthigayan; O'Neill, Christine F.; Parekh, Dipen J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Naylor, Susan L.; Lin, Shu; Sun, Lu-Zhe] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Livi, Carolina B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Livi, Carolina B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Yeh, I-Tien] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Block, Karen] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Sudarshan, Sunil; Shanmugasundaram, Karthigayan; Naylor, Susan L.; Lin, Shu; Livi, Carolina B.; O'Neill, Christine F.; Parekh, Dipen J.; Yeh, I-Tien; Sun, Lu-Zhe; Block, Karen] S Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX USA. RP Sudarshan, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. EM sudarshan@uthscsa.edu RI Lin, Shu/C-3790-2013 FU Cancer Therapy and Research Center (CTRC) at the University of Texas Health Science Center (National Institutes of Health ) [P30 CA054174-17]; NIH, AUA Foundation, HEB [K08 CA138774]; CTRC; NIH [U01 CA86402, R01 CA079683, R01 NCI CA131272]; Veterans Administration [CDA-2] FX This work was supported in part by the Cancer Therapy and Research Center (CTRC) at the University of Texas Health Science Center (National Institutes of Health P30 CA054174-17). SS is supported by NIH K08 CA138774, Voelcker Fund Young Investigator Award, AUA Foundation/Astellas Rising Star Award, and a special gift from Mr. Charles Butt and the employees of HEB. SLN is supported by the CTRC and NIH U01 CA86402. LZS is supported by NIH R01 CA079683. KB is supported by Veterans Administration Career Development Award (CDA-2) and NIH R01 NCI CA131272. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 17 Z9 19 U1 0 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 JUN 14 PY 2011 VL 6 IS 6 AR e21037 DI 10.1371/journal.pone.0021037 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 778EB UT WOS:000291682300024 PM 21695080 ER PT J AU Wu, YN Munhall, AC Johnson, SW AF Wu, Yan-Na Munhall, Adam C. Johnson, Steven W. TI Mitochondrial uncoupling agents antagonize rotenone actions in rat substantia nigra dopamine neurons SO BRAIN RESEARCH LA English DT Article DE Coenzyme Q(10); 2,4-dinitrophenol; FCCP; N-methyl-D-aspartate; Dopamine neuron; Uncoupling agent ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; METHYL-D-ASPARTATE; K-ATP CHANNELS; PARKINSONS-DISEASE; COMPLEX-I; COENZYME Q(10); OXIDATIVE STRESS; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; GLUTAMATE EXCITOTOXICITY; SUPEROXIDE-PRODUCTION AB Mild uncoupling of oxidative phosphorylation has been reported to reduce generation of reactive oxygen species (ROS) and therefore may be neuroprotective. We reported previously that the mitochondrial poison rotenone enhanced currents evoked by N-methyl-D-aspartate (NMDA) by a ROS-dependent mechanism in rat midbrain dopamine neurons. Thus, rotenone, which produces a model of Parkinson's disease in rodents, may increase the risk of dopamine neuron excitotoxicity. The purpose of this study was to test the hypothesis that oxidative phosphorylation uncoupling agents would antagonize the effect of rotenone on NMDA current. We used patch pipettes to record whole-cell currents under voltage-clamp (-60 mV) in substantia nigra dopamine neurons in slices of rat brain. Rotenone, NMDA and uncoupling agents were added to the brain slice superfusate. Inward currents evoked by NMDA (30 mu M) more than doubled in amplitude after slices were superfused for 30 min with 100 nM rotenone. Continuous superfusion with the uncoupling agent carbonyl cyanide-p-trifluoromethoxy-phenylhydrazone (1-3 nM) or 2,4-dinitrophenol (100 nM) significantly antagonized and delayed the ability of rotenone to potentiate NMDA currents. Coenzyme Q(10) (1-10 nM), which has been reported to facilitate uncoupling protein activity, also antagonized this action of rotenone. These results suggest that mild uncoupling of oxidative phosphorylation may protect dopamine neurons against injury from mitochondrial poisons such as rotenone. Published by Elsevier B.V. C1 [Wu, Yan-Na; Munhall, Adam C.; Johnson, Steven W.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Johnson, Steven W.] Portland VA Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. EM johnsost@ohsu.edu FU Veterans Affairs Merit Review grant [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 56 TC 9 Z9 9 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 13 PY 2011 VL 1395 BP 86 EP 93 DI 10.1016/j.brainres.2011.04.032 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 788DQ UT WOS:000292426000010 PM 21550595 ER PT J AU Figueira, CP Croda, J Choy, HA Haake, DA Reis, MG Ko, AI Picardeau, M AF Figueira, Claudio Pereira Croda, Julio Choy, Henry A. Haake, David A. Reis, Mitermayer G. Ko, Albert I. Picardeau, Mathieu TI Heterologous expression of pathogen-specific genes ligA and ligB in the saprophyte Leptospira biflexa confers enhanced adhesion to cultured cells and fibronectin SO BMC MICROBIOLOGY LA English DT Article ID IMMUNOGLOBULIN-LIKE PROTEIN; PROTECTIVE IMMUNITY; TARGETED MUTAGENESIS; ESCHERICHIA-COLI; HOST-CELLS; MDCK CELLS; C-TERMINUS; INTERROGANS; BINDING; INFECTION AB Background: In comparison to other bacterial pathogens, our knowledge of the molecular basis of the pathogenesis of leptospirosis is extremely limited. An improved understanding of leptospiral pathogenetic mechanisms requires reliable tools for functional genetic analysis. Leptospiral immunoglobulin-like (Lig) proteins are surface proteins found in pathogenic Leptospira, but not in saprophytes. Here, we describe a system for heterologous expression of the Leptospira interrogans genes ligA and ligB in the saprophyte Leptospira biflexa serovar Patoc. Results: The genes encoding LigA and LigB under the control of a constitutive spirochaetal promoter were inserted into the L. biflexa replicative plasmid. We were able to demonstrate expression and surface localization of LigA and LigB in L. biflexa. We found that the expression of the lig genes significantly enhanced the ability of transformed L. biflexa to adhere in vitro to extracellular matrix components and cultured cells, suggesting the involvement of Lig proteins in cell adhesion. Conclusions: This work reports a complete description of the system we have developed for heterologous expression of pathogen-specific proteins in the saprophytic L. biflexa. We show that expression of LigA and LigB proteins from the pathogen confers a virulence-associated phenotype on L. biflexa, namely adhesion to eukaryotic cells and fibronectin in vitro. This study indicates that L. biflexa can serve as a surrogate host to characterize the role of key virulence factors of the causative agent of leptospirosis. C1 [Picardeau, Mathieu] Inst Pasteur, Unite Biol Spirochetes, F-75724 Paris 15, France. [Figueira, Claudio Pereira; Croda, Julio; Reis, Mitermayer G.; Ko, Albert I.] Brazilian Minist Hlth, Oswaldo Cruz Fdn, Goncalo Moniz Res Ctr, BR-40295001 Salvador, BA, Brazil. [Choy, Henry A.; Haake, David A.] Vet Affairs Greater Los Angeles Hlth Care Syst, Div Infect Dis, Los Angeles, CA 90073 USA. [Choy, Henry A.; Haake, David A.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Ko, Albert I.] Yale Univ, Sch Med, Div Epidemiol Microbial Dis, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Croda, Julio] Fed Univ Grande Dourados, Fac Hlth Sci, Dourados, Brazil. RP Picardeau, M (reprint author), Inst Pasteur, Unite Biol Spirochetes, 28 Rue Docteur Roux, F-75724 Paris 15, France. EM mpicard@pasteur.fr RI Vacinas, Inct/J-9431-2013; Ko, Albert/P-2343-2015 OI Ko, Albert/0000-0001-9023-2339 FU Institut Pasteur, Paris, France; French Ministry of Research [ANR-08-MIE-018]; Oswaldo Cruz Foundation [PDTIS RVR05]; Brazilian National Research Council (INCTV); VA Medical Research Funds; National Institutes of Health [D43 TW00919, R01 AI34431, U01 AI088752] FX This work was supported by the Institut Pasteur, Paris, France; the French Ministry of Research ANR-08-MIE-018, the Fiocruz-Pasteur Scientific Cooperation Agreement, Oswaldo Cruz Foundation (PDTIS RVR05), Brazilian National Research Council (INCTV), VA Medical Research Funds, and the National Institutes of Health (grants D43 TW00919, R01 AI34431 and U01 AI088752). This research was conducted by C. P. Figueira in partial fulfillment of the requirements for a Ph.D. from Goncalo Moniz Research Center, Oswaldo Cruz Foundation, Brazil. NR 52 TC 29 Z9 30 U1 0 U2 4 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 JUN 9 PY 2011 VL 11 AR 129 DI 10.1186/1471-2180-11-129 PG 9 WC Microbiology SC Microbiology GA 790UK UT WOS:000292614500001 PM 21658265 ER PT J AU Hernandez-Corbacho, MJ Jenkins, RW Clarke, CJ Hannun, YA Obeid, LM Snider, AJ Siskind, LJ AF Hernandez-Corbacho, Maria Jose Jenkins, Russell W. Clarke, Christopher J. Hannun, Yusuf A. Obeid, Lina M. Snider, Ashley J. Siskind, Leah J. TI Accumulation of Long-Chain Glycosphingolipids during Aging Is Prevented by Caloric Restriction SO PLOS ONE LA English DT Article ID RENAL-CELL CARCINOMA; MEMBRANE-ASSOCIATED SIALIDASE; OXIDATIVE STRESS; INSULIN SENSITIVITY; RAT-KIDNEY; T-CELLS; NUTRITIONAL INFLUENCES; DIABETIC-NEPHROPATHY; ALZHEIMERS-DISEASE; FISCHER-344 RATS AB Background: Chronic kidney disease and end-stage renal disease are major causes of morbidity and mortality that are seen far more commonly in the aged population. Interestingly, kidney function declines during aging even in the absence of underlying renal disease. Declining renal function has been associated with age-related cellular damage and dysfunction with reports of increased levels of apoptosis, necrosis, and inflammation in the aged kidney. Bioactive sphingolipids have been shown to regulate these same cellular processes, and have also been suggested to play a role in aging and cellular senescence. Methodology/Principal Findings: We hypothesized that alterations in kidney sphingolipids play a role in the declining kidney function that occurs during aging. To begin to address this, the sphingolipid profile was measured in young (3 mo), middle aged (9 mo) and old (17 mo) C57BL/6 male mice. Interestingly, while modest changes in ceramides and sphingoid bases were evident in kidneys from older mice, the most dramatic elevations were seen in long-chain hexosylceramides (HexCer) and lactosylceramides (LacCer), with C14-and C16-lactosylceramides elevated as much as 8 and 12-fold, respectively. Increases in long-chain LacCers during aging are not exclusive to the kidney, as they also occur in the liver and brain. Importantly, caloric restriction, previously shown to prevent the declining kidney function seen in aging, inhibits accumulation of long-chain HexCer/LacCers and prevents the age-associated elevation of enzymes involved in their synthesis. Additionally, long-chain LacCers are also significantly elevated in human fibroblasts isolated from elderly individuals. Conclusion/Significance: This study demonstrates accumulation of the glycosphingolipids HexCer and LacCer in several different organs in rodents and humans during aging. In addition, data demonstrate that HexCer and LacCer metabolism is regulated by caloric restriction. Taken together, data suggest that HexCer/LacCers are important mediators of cellular processes fundamental to mammalian aging. C1 [Hernandez-Corbacho, Maria Jose; Obeid, Lina M.; Snider, Ashley J.; Siskind, Leah J.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Jenkins, Russell W.; Clarke, Christopher J.; Hannun, Yusuf A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Obeid, Lina M.; Snider, Ashley J.; Siskind, Leah J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Hernandez-Corbacho, MJ (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. EM siskind@musc.edu OI obeid, lina/0000-0002-0734-0847 FU VA Merit; VA; VA REAP; American Cancer Society [IRG-97-219-11]; NIH/NCRR [P30 CA138313, P20 RR17677]; American Heart Association [AHA 081509E]; NIH [GM08716, GM-43825]; MUSC Hollings Cancer Center Abney Foundation; NIH/NIA [R01 AG016583] FX This work is supported by: VA Merit (to L.M.O.), VA CDA-2 Awards (to L.J.S. and A.J.S.), pilot project from the VA REAP (to L.J.S., A.J.S., and L.M.O.), the American Cancer Society Institutional Research Grant # IRG-97-219-11 (subaward to L.J.S.), Lipidomics Shared Resource of the Hollings Cancer Center supported by a Cancer Center Support Grant (P30 CA138313), pilot project (to L.J.S) from the NIH/NCRR P20 RR17677 COBRE in Lipidomics and Pathobiology, American Heart Association Pre-Doctoral Fellowship (AHA 081509E - to R.W.J.), NIH MSTP Training Grant (GM08716 - to R.W.J.), MUSC Hollings Cancer Center Abney Foundation Scholarship (to R.W.J.), and NIH/NIA R01 AG016583 (L.M.O.) and NIH GM-43825 (YAH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 88 TC 12 Z9 13 U1 1 U2 5 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 JUN 8 PY 2011 VL 6 IS 6 AR e20411 DI 10.1371/journal.pone.0020411 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 777JJ UT WOS:000291611500023 PM 21687659 ER PT J AU Ryoo, JJ Malin, JL AF Ryoo, Joan J. Malin, Jennifer L. TI Reconsidering the Veterans Health Administration: A Model and a Moment for Publicly Funded Health Care Delivery SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID QUALITY-OF-CARE; MYOCARDIAL-INFARCTION; SYSTEM; PROSTATE; TRANSFORMATION; MORTALITY; TRIAL C1 [Malin, Jennifer L.] Vet Affairs Greater Los Angeles Healthcare Syst, W Angeles Med Ctr, Div Hematol Oncol, Dept Internal Med, Los Angeles, CA 90073 USA. [Ryoo, Joan J.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. RP Malin, JL (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, W Angeles Med Ctr, Div Hematol Oncol, Dept Internal Med, 11301 Wilshire Blvd,4th Floor, Los Angeles, CA 90073 USA. EM jennifer.malin@va.gov NR 19 TC 4 Z9 4 U1 1 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 7 PY 2011 VL 154 IS 11 DI 10.7326/0003-4819-154-11-201106070-00010 PG 34 WC Medicine, General & Internal SC General & Internal Medicine GA 773MV UT WOS:000291312300009 PM 21646560 ER PT J AU Slatore, CG Gould, MK Au, DH Deffebach, ME White, E AF Slatore, Christopher G. Gould, Michael K. Au, David H. Deffebach, Mark E. White, Emily TI Lung cancer stage at diagnosis: Individual associations in the prospective VITamins and lifestyle (VITAL) cohort SO BMC CANCER LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; GUIDELINES 2ND EDITION; SURVIVAL; CT; OVERDIAGNOSIS; SURVEILLANCE; MANAGEMENT; EDUCATION; OUTCOMES; SOCIETY AB Background: Lung cancer is the leading cause of cancer death in the United States. Identifying factors associated with stage of diagnosis can improve our understanding of biologic and behavioral pathways of lung cancer development and detection. We used data from a prospective cohort study to evaluate associations of demographic, health history, and health behaviors with early versus late stage at diagnosis of non-small cell lung cancer (NSCLC). Methods: We calculated odds ratios (ORs) for the association of patient-level characteristics with advanced stage of diagnosis for NSCLC. The OR's were then adjusted for age, gender, race/ethnicity, smoking status, income, education, chronic obstructive pulmonary disease, and a comorbidity index. Results: We identified 612 cases of NSCLC among 77,719 adults, aged 50 to 76 years from Washington State recruited in 2000-2002, with followup through December 2007. In univariate analyses, subjects who quit smoking <10 years (OR 2.56, 95% CI 1.17 - 5.60) and were college graduates (OR 1.67, 95% CI, 1.00 - 2.76) had increased risks of being diagnosed with advanced stage NSCLC, compared to never smokers and non-college graduates, respectively. Receipt of sigmoidoscopy/colonoscopy, compared to no receipt, was associated with a decreased risk of advanced stage (OR 0.65, 95% CI, 0.43 - 0.99). The adjusted OR for receipt of sigmoidoscopy/colonoscopy was 0.55 (95% CI, 0.36 - 0.86). There was evidence that increasing the number of screening activities was associated with a decreased risk of advanced stage NSCLC (P for trend = 0.049). Conclusions: Smoking status, education, and a screening activity were associated with stage at diagnosis of NSCLC. These results may guide future studies of the underlying mechanisms that influence how NSCLC is detected and diagnosed. C1 [Slatore, Christopher G.; Deffebach, Mark E.] Portland VA Med Ctr, Portland, OR USA. [Slatore, Christopher G.; Deffebach, Mark E.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Gould, Michael K.] Univ So Calif, Keck Sch Med, Div Pulm & Crit Care Med, Los Angeles, CA 90033 USA. [Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Au, David H.] Univ Washington, Div Pulm & Crit Care, Seattle, WA 98195 USA. [White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [White, Emily] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. RP Slatore, CG (reprint author), Portland VA Med Ctr, Portland, OR USA. EM christopher.slatore@va.gov OI Slatore, Christopher/0000-0003-0958-8122 FU CHEST Foundation of the American College of Chest Physicians; LUNGevity Foundation; National Institutes of Health [CA74846]; Department of Veterans Affairs; Portland VA Medical Center, Portland, OR; VA Puget Sound Health Care System, Seattle, Washington FX This work was completed with grant support from the CHEST Foundation of the American College of Chest Physicians and the LUNGevity Foundation to C. S. This work was also supported by the National Institutes of Health [CA74846 to EW]. Drs. Slatore, Au, and Deffebach were supported by the Department of Veterans Affairs. This study is the result of work supported by resources from the Portland VA Medical Center, Portland, OR, and VA Puget Sound Health Care System, Seattle, Washington. The study sponsors had no role in the conduct of the study, in the collection, management, analysis, or interpretation of data, or in the preparation, review, or approval of the manuscript. NR 31 TC 6 Z9 6 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD JUN 7 PY 2011 VL 11 AR 228 DI 10.1186/1471-2407-11-228 PG 7 WC Oncology SC Oncology GA 786VF UT WOS:000292335300001 PM 21649915 ER PT J AU Gebregziabher, M Lynch, CP Mueller, M Gilbert, GE Echols, C Zhao, YM Egede, LE AF Gebregziabher, Mulugeta Lynch, Cheryl P. Mueller, Martina Gilbert, Gregory E. Echols, Carrae Zhao, Yumin Egede, Leonard E. TI Using quantile regression to investigate racial disparities in medication non-adherence SO BMC MEDICAL RESEARCH METHODOLOGY LA English DT Article DE Medication adherence; Quantile regression; Diabetes; Health disparities ID RETROSPECTIVE COHORT; DENSITY REGRESSION; DIABETES-MELLITUS; CLAIMS DATA; ADHERENCE; HOSPITALIZATION; PREVALENCE; PREDICTORS; ALGORITHM; DATABASES AB Background: Many studies have investigated racial/ethnic disparities in medication non-adherence in patients with type 2 diabetes using common measures such as medication possession ratio (MPR) or gaps between refills. All these measures including MPR are quasi-continuous and bounded and their distribution is usually skewed. Analysis of such measures using traditional regression methods that model mean changes in the dependent variable may fail to provide a full picture about differential patterns in non-adherence between groups. Methods: A retrospective cohort of 11,272 veterans with type 2 diabetes was assembled from Veterans Administration datasets from April 1996 to May 2006. The main outcome measure was MPR with quantile cutoffs Q1-Q4 taking values of 0.4, 0.6, 0.8 and 0.9. Quantile-regression (QReg) was used to model the association between MPR and race/ethnicity after adjusting for covariates. Comparison was made with commonly used ordinary-least-squares (OLS) and generalized linear mixed models (GLMM). Results: Quantile-regression showed that Non-Hispanic-Black (NHB) had statistically significantly lower MPR compared to Non-Hispanic-White (NHW) holding all other variables constant across all quantiles with estimates and p-values given as -3.4% (p = 0.11), -5.4% (p = 0.01), -3.1% (p = 0.001), and -2.00% (p = 0.001) for Q1 to Q4, respectively. Other racial/ethnic groups had lower adherence than NHW only in the lowest quantile (Q1) of about -6.3% (p = 0.003). In contrast, OLS and GLMM only showed differences in mean MPR between NHB and NHW while the mean MPR difference between other racial groups and NHW was not significant. Conclusion: Quantile regression is recommended for analysis of data that are heterogeneous such that the tails and the central location of the conditional distributions vary differently with the covariates. QReg provides a comprehensive view of the relationships between independent and dependent variables (i.e. not just centrally but also in the tails of the conditional distribution of the dependent variable). Indeed, without performing QReg at different quantiles, an investigator would have no way of assessing whether a difference in these relationships might exist. C1 [Lynch, Cheryl P.; Gilbert, Gregory E.; Echols, Carrae; Egede, Leonard E.] Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Gebregziabher, Mulugeta; Lynch, Cheryl P.; Zhao, Yumin; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC USA. [Gebregziabher, Mulugeta; Mueller, Martina] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC USA. [Mueller, Martina] Med Univ S Carolina, Coll Nursing, Charleston, SC USA. RP Egede, LE (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. EM egedel@musc.edu RI Gilbert, Gregory/C-7735-2016 OI Gilbert, Gregory/0000-0003-0879-5496; Gebregziabher, Mulugeta/0000-0002-4826-481X FU Veterans Affairs Health Services Research and Development [REA 08-261] FX This study was supported by Grant # REA 08-261, Center for Disease Prevention and Health Interventions for Diverse Populations funded by Veterans Affairs Health Services Research and Development (PI - Leonard Egede). NR 40 TC 15 Z9 15 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2288 J9 BMC MED RES METHODOL JI BMC Med. Res. Methodol. PD JUN 6 PY 2011 VL 11 AR 88 DI 10.1186/1471-2288-11-88 PG 11 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 781QT UT WOS:000291949300002 PM 21645379 ER PT J AU Sawers, A Hahn, ME AF Sawers, Andrew Hahn, Michael E. TI Trajectory of the center of rotation in non-articulated energy storage and return prosthetic feet SO JOURNAL OF BIOMECHANICS LA English DT Article DE Prosthetic feet; Helical axis; Link-segment model; Amputee; Artificial limb ID HUMAN JOINT KINEMATICS; HELICAL AXIS; CENTER LOCATION; AMPUTEE GAIT; KNEE; MOTION; PARAMETERS; AMPUTATION; MARKERS; MOMENT AB Non-articulated energy storage and return prosthetic feet lack any true articulation or obvious point of rotation. This makes it difficult to select a joint center about which to estimate their kinetics. Despite this absence of any clear point of rotation, methods for estimating the kinetic performance of this class of prosthetic feet typically assume that they possess a fixed center of rotation and that its location is well approximated by the position of the contralateral lateral malleolus. To evaluate the validity of this assumption we used a finite helical axis approach to determine the position of the center of rotation in the sagittal plane for a series of non-articulated energy storage and return prosthetic feet. We found that over the course of stance phase, the sagittal finite helical axis position diverged markedly from the typically assumed fixed axis location. These results suggest that researchers may need to review center of rotation assumptions when assessing prosthetic foot kinetics, while clinicians may need to reconsider the criteria by which they prescribe these prosthetic feet. Published by Elsevier Ltd. C1 [Sawers, Andrew; Hahn, Michael E.] VA Puget Sound, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, Dept Vet Affairs VA, Seattle, WA 98108 USA. [Sawers, Andrew] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Hahn, Michael E.] Univ Washington, Dept Mech Engn, Seattle, WA 98105 USA. RP Hahn, ME (reprint author), VA Puget Sound, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, Dept Vet Affairs VA, 1660 S Columbian Way, Seattle, WA 98108 USA. EM mehahn@uw.edu FU American Society of Biomechanics; Orthotic and Prosthetic Education and Research Foundation [OPERF-2009-FA-1]; Center for Orthotics and Prosthetics Learning and Outcomes/Evidence-Based Practice (COPL); Department of Veterans Affairs, Rehabilitation Research and Development Service [A4883C] FX This research was supported in part by a Graduate Student Grant-in-Aid from the American Society of Biomechanics, a Graduate Fellow Research Award from the Orthotic and Prosthetic Education and Research Foundation (OPERF-2009-FA-1), a Research Award from the Center for Orthotics and Prosthetics Learning and Outcomes/Evidence-Based Practice (COPL) and a Center of Excellence grant (A4883C), Department of Veterans Affairs, Rehabilitation Research and Development Service. NR 28 TC 7 Z9 7 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD JUN 3 PY 2011 VL 44 IS 9 BP 1673 EP 1677 DI 10.1016/j.jbiomech.2011.03.028 PG 5 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 780HY UT WOS:000291846300006 PM 21481878 ER PT J AU Kendall, RT Strungs, EG Rachidi, SM Lee, MH El-Shewy, HM Luttrell, DK Janech, MG Luttrell, LM AF Kendall, Ryan T. Strungs, Erik G. Rachidi, Saleh M. Lee, Mi-Hye El-Shewy, Hesham M. Luttrell, Deirdre K. Janech, Michael G. Luttrell, Louis M. TI The beta-Arrestin Pathway-selective Type 1A Angiotensin Receptor (AT(1A)) Agonist [Sar(1), Ile(4), Ile(8)] Angiotensin II Regulates a Robust G Protein-independent Signaling Network SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE-CELLS; ACTIVATION; PHOSPHORYLATION; KINASE; SET; CYCLOOXYGENASE-1; BETA-ARRESTIN-2; STIMULATION; COMPLEXES; SYNTHASE AB The angiotensin II peptide analog [Sar(1), Ile(4), Ile(8)] AngII (SII) is a biased AT(1A) receptor agonist that stimulates receptor phosphorylation, beta-arrestin recruitment, receptor internalization, and beta-arrestin-dependent ERK1/2 activation without activating heterotrimeric G-proteins. To determine the scope of G-protein- independent AT(1A) receptor signaling, we performed a gelbased phosphoproteomic analysis of AngII and SII-induced signaling in HEK cells stably expressing AT(1A) receptors. A total of 34 differentially phosphorylated proteins were detected, of which 16 were unique to SII and eight to AngII stimulation. MALDI-TOF/TOF mass fingerprinting was employed to identify 24 SII-sensitive phosphoprotein spots, of which three (two peptide inhibitors of protein phosphatase 2A (I1PP2A and I2PP2A) and prostaglandin E synthase 3 (PGES3)) were selected for validation and further study. We found that phosphorylation of I2PP2A was associated with rapid and transient inhibition of a beta-arrestin 2-associated pool of protein phosphatase 2A, leading to activation of Akt and increased phosphorylation of glycogen synthase kinase 3 beta in an arrestin signalsome complex. SII-stimulated PGES3 phosphorylation coincided with an increase in beta-arrestin 1-associated PGES3 and an arrestin-dependent increase in cyclooxygenase 1-dependent prostaglandin E-2 synthesis. These findings suggest that AT(1A) receptors regulate a robust G protein-independent signaling network that affects protein phosphorylation and autocrine/paracrine prostaglandin production and that these pathways can be selectively modulated by biased ligands that antagonize G protein activation. C1 [Kendall, Ryan T.; Strungs, Erik G.; Rachidi, Saleh M.; Lee, Mi-Hye; El-Shewy, Hesham M.; Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Luttrell, Deirdre K.; Janech, Michael G.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Janech, Michael G.; Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,MSC 624, Charleston, SC 29425 USA. EM luttrell@musc.edu OI Janech, Michael/0000-0002-3202-4811 FU National Institutes of Health [R01 DK055524, T32 HL07260]; Research Service of the Ralph H. Johnson Veterans Affairs Medical Center; Nephcure Young Investigator Award; Cancer Center [P30 CA138313]; Department of Veterans Affairs FX This work was supported, in whole or in part, by National Institutes of Health Grants R01 DK055524 (to L. M. L.) and T32 HL07260 (to R. T. K.). This work was also supported by the Research Service of the Ralph H. Johnson Veterans Affairs Medical Center (to L. M. L. and M. G. J.) and the Nephcure Young Investigator and Department of Veterans Affairs Career Development Awards (to M. G. J.). Imaging facilities for this research were supported, in part, by Cancer Center Support Grant P30 CA138313 (to the Hollings Cancer Center, Medical University of South Carolina). NR 33 TC 31 Z9 32 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 3 PY 2011 VL 286 IS 22 BP 19880 EP 19891 DI 10.1074/jbc.M111.233080 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 769OZ UT WOS:000291027700068 PM 21502318 ER PT J AU Salas, A Ponnusamy, S Senkal, CE Meyers-Needham, M Selvam, SP Saddoughi, SA Apohan, E Sentelle, RD Smith, C Gault, CR Obeid, LM El-Shewy, HM Oaks, J Santhanam, R Marcucci, G Baran, Y Mahajan, S Fernandes, D Stuart, R Perrotti, D Ogretmen, B AF Salas, Arelis Ponnusamy, Suriyan Senkal, Can E. Meyers-Needham, Marisa Selvam, Shanmugam Panneer Saddoughi, Sahar A. Apohan, Elif Sentelle, R. David Smith, Charles Gault, Christopher R. Obeid, Lina M. El-Shewy, Hesham M. Oaks, Joshua Santhanam, Ramasamy Marcucci, Guido Baran, Yusuf Mahajan, Sandeep Fernandes, Daniel Stuart, Robert Perrotti, Danilo Ogretmen, Besim TI Sphingosine kinase-1 and sphingosine 1-phosphate receptor 2 mediate Bcr-Abl1 stability and drug resistance by modulation of protein phosphatase 2A SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; IMATINIB-INDUCED APOPTOSIS; ABL TYROSINE KINASE; BCR-ABL; INHIBITOR STI571; CANCER-CELLS; GENE; SPHINGOSINE-1-PHOSPHATE; MECHANISMS AB The mechanisms by which sphingosine kinase-1 (SK-1)/sphingosine 1-phosphate (S1P) activation contributes to imatinib resistance in chronic myeloid leukemia (CML) are unknown. We show herein that increased SK-1/S1P enhances Bcr-Abl1 protein stability, through inhibition of its proteasomal degradation in imatinibresistant K562/IMA-3 and LAMA-4/IMA human CML cells. In fact, Bcr-Abl1 stability was enhanced by ectopic SK-1 expression. Conversely, siRNA-mediated SK-1 knockdown in K562/IMA-3 cells, or its genetic loss in SK-1(-/-) MEFs, significantly reduced Bcr-Abl1 stability. Regulation of Bcr-Abl1 by SK-1/S1P was dependent on S1P receptor 2 (S1P2) signaling, which prevented Bcr-Abl1 dephosphorylation, and degradation via inhibition of PP2A. Molecular or pharmacologic interference with SK-1/S1P2 restored PP2A-dependent Bcr-Abl1 dephosphorylation, and enhanced imatinib-or nilotinib-induced growth inhibition in primary CD34(+) mononuclear cells obtained from chronic phase and blast crisis CML patients, K562/IMA-3 or LAMA4/IMA cells, and 32Dcl3 murine progenitor cells, ex-pressing the wild-type or mutant (Y253H or T315I) Bcr-Abl1 in situ. Accordingly, impaired SK-1/S1P2 signaling enhanced the growth-inhibitory effects of nilotinib against 32D/T315I-Bcr-Abl1-derived mouse allografts. Since SK-1/S1P/S1P2 signaling regulates Bcr-Abl1 stability via modulation of PP2A, inhibition of SK-1/S1P2 axis represents a novel approach to target wild-type-ormutant-Bcr-Abl1 thereby overcoming drug resistance. (Blood. 2011; 117(22): 5941-5952) C1 [Salas, Arelis; Ponnusamy, Suriyan; Senkal, Can E.; Meyers-Needham, Marisa; Selvam, Shanmugam Panneer; Saddoughi, Sahar A.; Apohan, Elif; Sentelle, R. David; Gault, Christopher R.; Baran, Yusuf; Mahajan, Sandeep; Fernandes, Daniel; Ogretmen, Besim] Ralph H Johnson Vet Adm Hosp, Dept Biochem & Mol Biol, Charleston, SC USA. [Salas, Arelis; Ponnusamy, Suriyan; Senkal, Can E.; Meyers-Needham, Marisa; Selvam, Shanmugam Panneer; Saddoughi, Sahar A.; Apohan, Elif; Sentelle, R. David; Smith, Charles; Gault, Christopher R.; Obeid, Lina M.; Baran, Yusuf; Mahajan, Sandeep; Fernandes, Daniel; Stuart, Robert; Ogretmen, Besim] Ralph H Johnson Vet Adm Hosp, Hollings Canc Ctr, Charleston, SC USA. [Smith, Charles] Ralph H Johnson Vet Adm Hosp, Dept Pharmaceut Sci, Charleston, SC USA. [Obeid, Lina M.] Ralph H Johnson Vet Adm Hosp, Div Internal Med, Charleston, SC USA. [El-Shewy, Hesham M.; Perrotti, Danilo] Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29425 USA. [Oaks, Joshua; Santhanam, Ramasamy; Marcucci, Guido] Ohio State Univ, Human Canc Genet Program, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. RP Ogretmen, B (reprint author), 86 Jonathan Lucas St,Rm HO512A-B, Charleston, SC 29425 USA. EM ogretmen@musc.edu RI Perrotti, Danilo/E-3852-2011 OI Stuart, Robert/0000-0001-7549-8008; obeid, lina/0000-0002-0734-0847 FU National Institutes of Health (NIH) [CA088932, DE016572, CA097132, CA095512]; US Army [W81XWH-07-1-0270]; NIH, National Center for Research Resources [C06 RR015455] FX This work was supported by research grants from the National Institutes of Health (NIH; CA088932, DE016572, and CA097132 to B.O., and CA095512 to D.P.) and the US Army (CML Research Program, W81XWH-07-1-0270 to D. P.). D.P. is a Scholar of The Leukemia & Lymphoma Society. A.S. was supported by the Minority Fellowship grant from the NIH. Lipid measurements and animal studies were conducted in facilities constructed with support from the NIH (C06 RR015455), at the Extramural Research Facilities Program of the National Center for Research Resources. NR 50 TC 50 Z9 51 U1 1 U2 17 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 JUN 2 PY 2011 VL 117 IS 22 BP 5941 EP 5952 DI 10.1182/blood-2010-08-300772 PG 12 WC Hematology SC Hematology GA 772BA UT WOS:000291203200022 PM 21527515 ER PT J AU Vizueta, N Townsend, JD Torrisi, S Moody, TD Fischer, J Aquino, AR Bookheimera, SY Altshuler, LL AF Vizueta, N. Townsend, J. D. Torrisi, S. Moody, T. D. Fischer, J. Aquino, A. R. Bookheimera, S. Y. Altshuler, L. L. TI Emotion regulation and functional magnetic resonance imaging in bipolar II depression vs. major depressive disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 9th International Conference on Bipolar Disorder CY JUN 09-11, 2011 CL Pittsburgh, PA DE bipolar II disorder; functional MRI; emotional faces; major depressive disorder C1 [Vizueta, N.; Townsend, J. D.; Torrisi, S.; Moody, T. D.; Fischer, J.; Aquino, A. R.; Altshuler, L. L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Vizueta, N.; Townsend, J. D.; Torrisi, S.; Moody, T. D.; Fischer, J.; Aquino, A. R.; Altshuler, L. L.] Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Altshuler, L. L.] VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Dept Psychiat, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2011 VL 13 SU 1 SI SI BP 26 EP 26 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 889VH UT WOS:000300102400038 ER PT J AU Stengel, A Tache, Y AF Stengel, Andreas Tache, Yvette TI Ghrelin: New Insight to Mechanisms and Treatment of Postoperative Gastric Ileus SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE abdominal surgery; desacyl ghrelin; drug treatment; ghrelin-O-acyltransferase; GOAT ID CORTICOTROPIN-RELEASING-FACTOR; DES-ACYL GHRELIN; HORMONE SECRETAGOGUE RECEPTOR; CONSCIOUS FED RATS; STIMULATES FOOD-INTAKE; III-LIKE CONTRACTIONS; GENE-RELATED PEPTIDE; ABDOMINAL-SURGERY; ELECTRICAL-STIMULATION; AGONIST TZP-101 AB Postoperative gastric ileus develops after abdominal surgery and if prolonged leads to longer hospitalization times. Besides discomfort for the patient such as abdominal bloating and pain, this condition is associated with a great increase in healthcare costs. In order to develop new and effective treatment strategies to alleviate the ileus, a good understanding of the pathophysiological underlying mechanisms is necessary. Postoperative gastric ileus consists of two phases, a first neural/humoral phase and a second inflammatory phase. The present review will focus on the role of the orexigenic and prokinetic hormone ghrelin in the development of postoperative ileus. Although ghrelin and ghrelin mimetics have been used during the recent years in pre-clinical and a first clinical trial to alleviate symptoms of postoperative ileus, the regulation of this hormone under conditions of abdominal surgery has just recently begun to be explored. Growing evidence indicates that postoperative restoration of ghrelin signaling leads to an orexigenic effect whereas the gastroprokinetic actions seem to require supraphysiological doses. Since the expression of ghrelin-O-acyltransferase (GOAT), the only ghrelin acylating enzyme, is reduced after abdominal surgery, the stimulation of GOAT signaling may also be a new promising approach to restore levels of acyl ghrelin under these conditions and a potential useful addition to ghrelin mimetics. C1 [Tache, Yvette] VA Greater Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. [Stengel, Andreas] Charite Med Ctr, Dept Med, Div Psychosomat Med, Berlin, Germany. [Stengel, Andreas] Univ Berlin, Berlin, Germany. [Stengel, Andreas; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Div Digest Dis, Los Angeles, CA 90095 USA. [Stengel, Andreas; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Div Digest Dis, Los Angeles, CA 90095 USA. RP Tache, Y (reprint author), VA Greater Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU VA Research Career Scientist Award; VA Merit Award; NIH [DK 33061, DK57238] FX Y.T. is in receipt of VA Research Career Scientist Award, VA Merit Award and NIH R01grants DK 33061 and DK57238. We thank Ms. Eugenia Hu for careful reading of the manuscript. NR 137 TC 11 Z9 11 U1 0 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD JUN PY 2011 VL 17 IS 16 BP 1587 EP 1593 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 883FM UT WOS:000299619600009 PM 21548864 ER PT J AU Jurgens, CA Toukatly, MN Fligner, CL Udayasankar, J Subramanian, SL Zraika, S Aston-Mourney, K Carr, DB Westermark, P Westermark, GT Kahn, SE Hull, RL AF Jurgens, Catherine A. Toukatly, Mirna N. Fligner, Corinne L. Udayasankar, Jayalakshmi Subramanian, Shoba L. Zraika, Sakeneh Aston-Mourney, Kathryn Carr, Darcy B. Westermark, Per Westermark, Gunilla T. Kahn, Steven E. Hull, Rebecca L. TI beta-Cell Loss and beta-Cell Apoptosis in Human Type 2 Diabetes Are Related to Islet Amyloid Deposition SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GLUCOSE-TOLERANCE; MOUSE MODEL; POLYPEPTIDE; INSULIN; LANGERHANS; PANCREAS; MELLITUS; MASS; DYSFUNCTION; EXPRESSION AB Amyloid deposition and reduced beta-cell mass are pathological hallmarks of the pancreatic islet in type 2 diabetes; however, whether the extent of amyloid deposition is associated with decreased beta-cell mass is debated. We investigated the possible relationship and, for the first time, determined whether increased islet amyloid and/or decreased beta-cell area quantified on histological sections is correlated with increased beta-cell apoptosis. Formalin-fixed, paraffin-embedded human pancreas sections from subjects with (n = 29) and without (n = 39) diabetes were obtained at autopsy (64 +/- 2 and 70 +/- 4 islets/subject, respectively). Amyloid and beta cells were visualized by thioflavin S and insulin inununolabeling. Apoptotic beta cells were detected by colabeling for insulin and by TUNEL. Diabetes was associated with increased amyloid deposition, decreased beta-cell area, and increased beta-cell apoptosis, as expected. There was a strong inverse correlation between beta-cell area and amyloid deposition (r = -0.42, P < 0.001). beta-Cell area was selectively reduced in individual amyloid-containing islets from diabetic subjects, compared with control subjects, but amyloid-free islets had beta-cell area equivalent to islets from control subjects. Increased amyloid 'deposition was associated with beta-cell apoptosis (r = 0.56, P < 0.01). Thus, islet amyloid is associated with decreased beta-cell area and increased beta-cell apoptosis, suggesting that islet amyloid deposition contributes to the decreased beta-cell mass that characterizes type 2 diabetes. (Am J Pathol 2011, 178:2632-2640; DOI: 10.1016/j.ajpath.2011.02.036) C1 [Jurgens, Catherine A.; Toukatly, Mirna N.; Udayasankar, Jayalakshmi; Subramanian, Shoba L.; Zraika, Sakeneh; Aston-Mourney, Kathryn; Kahn, Steven E.; Hull, Rebecca L.] Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Fligner, Corinne L.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Carr, Darcy B.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Westermark, Per] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden. [Westermark, Gunilla T.] Uppsala Univ, Dept Med Cell Biol, Uppsala, Sweden. RP Hull, RL (reprint author), VA Puget Sound Hlth Care Syst 151, 1660 S Columbian Way, Seattle, WA 98108 USA. EM rhull@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU U.S. Department of Veterans Affairs, VA Puget Sound Health Care System, Seattle, Washington; NIH [P30-DK17047, K01-DK74404, R01-DK75998, T32-DK07247, K99-DK80945]; American Diabetes Association; Swedish Research Council; Swedish Diabetes Association; European Union; Family Ernfors Fund; Juvenile Diabetes Research Foundation; McAbee; University of Washington; NIH-National Institute of Diabetes and Digestive and Kidney Diseases FX Supported by the U.S. Department of Veterans Affairs, VA Puget Sound Health Care System, Seattle, Washington; NIH grants P30-DK17047, K01-DK74404 (R.L.H.); R01-DK75998 (S.E.K.); T32-DK07247, and K99-DK80945 (S.Z.); the American Diabetes Association (S.E.K.); the Swedish Research Council (P.W. and G.T.W.); the Swedish Diabetes Association (G.T.W.); European Union FW6 program EURAMY (P.W. and G.T.W.); the Family Ernfors Fund; a Juvenile Diabetes Research Foundation Postdoctoral Fellowship Award (J.U.); a McAbee Fellowship (K.A.-M.); the University of Washington Medical Student Research Training Program (M.N.T); and by the NIH-National Institute of Diabetes and Digestive and Kidney Diseases Medical Research Program in Diabetes. NR 33 TC 80 Z9 86 U1 1 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2011 VL 178 IS 6 BP 2632 EP 2640 DI 10.1016/j.ajpath.2011.02.036 PG 9 WC Pathology SC Pathology GA 865JJ UT WOS:000298306900019 PM 21641386 ER PT J AU Batki, SL Lasher, BA Herbst, E Prathikanthi, S Waldrop, A Neylan, TC Metzler, T Petrakis, I Tarasovsky, G Coetzee, J AF Batki, S. L. Lasher, B. A. Herbst, E. Prathikanthi, S. Waldrop, A. Neylan, T. C. Metzler, T. Petrakis, I. Tarasovsky, G. Coetzee, J. TI RECRUITMENT AND CHARACTERISTICS OF VETERANS WITH PTSD AND ALCOHOL USE DISORDERS ENTERING A PHARMACOTHERAPY TRIAL SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 UCSF, Dept Psychiat, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 JUN PY 2011 VL 35 IS 6 SU S BP 19A EP 19A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804300035 ER PT J AU Durazzo, TC Tosun, D Mon, A Buckley, S Gazdzinski, S Fryer, SL Meyerhoff, DJ AF Durazzo, T. C. Tosun, D. Mon, A. Buckley, S. Gazdzinski, S. Fryer, S. L. Meyerhoff, D. J. TI MORPHOLOGY OF THE BRAIN REWARD SYSTEM: RELATIONSHIP TO RELAPSE AND EXTENDED ABSTINENCE IN ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 [Durazzo, T. C.; Tosun, D.; Mon, A.; Buckley, S.; Gazdzinski, S.; Fryer, S. L.; Meyerhoff, D. J.] Univ Calif San Francisco, Ctr Imaging Neurodegenerat Dis, San Francisco VA Med Ctr, Dept Radiol & Biomed Imaging, San Francisco, CA 94121 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2011 VL 35 IS 6 SU S BP 25A EP 25A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804300059 ER PT J AU Raskind, MA Redila, VA Olson, VG AF Raskind, M. A. Redila, V. A. Olson, Valerie G. TI PRAZOSIN BLOCKS DEVELOPMENT OF ETHANOL, MORPHINE, AND COCAINE CONDITIONED PLACE PREFERENCE IN MICE. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 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 JUN PY 2011 VL 35 IS 6 SU S BP 66A EP 66A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804300223 ER PT J AU Luterek, JA Simpson, TL Gurrad, B Rosenthal, C Kaysen, D AF Luterek, J. A. Simpson, T. L. Gurrad, B. Rosenthal, C. Kaysen, D. TI EFFICACY OF DECREASING ALCOHOL CRAVINGS WITH COGNITIVE RESTRUCTURING AND ACCEPTANCE IN INDIVIDUALS WITH ALCOHOL DEPENDENCE/PTSD USING A LAB ANALOG SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 JUN PY 2011 VL 35 IS 6 SU S BP 81A EP 81A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804300283 ER PT J AU Mon, A Durazzo, TC Delucchi, KL Meyerhoff, DJ AF Mon, A. Durazzo, T. C. Delucchi, K. L. Meyerhoff, D. J. TI ACCURATE PREDICTION OF BRAIN TISSUE VOLUME RECOVERY IN ABSTINENT ALCOHOLICS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 Univ Calif San Francisco, Ctr Imaging Neurodegenerat Dis, San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2011 VL 35 IS 6 SU S BP 129A EP 129A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804300475 ER PT J AU Durazzo, TC Hutchison, K Fryer, SL Mon, A Meyerhoff, DJ AF Durazzo, T. C. Hutchison, K. Fryer, S. L. Mon, A. Meyerhoff, D. J. TI ASSOCIATIONS OF BDNF, COMT AND DRD2 POLYMORPHISMS AND CHRONIC CIGARETTE SMOKING WITH NEUROCOGNITION IN ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 [Durazzo, T. C.; Hutchison, K.; Fryer, S. L.; Mon, A.; Meyerhoff, D. J.] Univ Calif San Francisco, Ctr Imaging Neurodegenerat Dis, San Francisco VA Med Ctr, Dept Radiol & Biomed Imaging, San Francisco, CA 94121 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2011 VL 35 IS 6 SU S BP 134A EP 134A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804300496 ER PT J AU Meyerhoff, DJ Durazzo, TC Hutchison, K Mon, A AF Meyerhoff, D. J. Durazzo, T. C. Hutchison, K. Mon, A. TI ASSOCIATIONS BETWEEN BDNF VAL66MET GENOTYPE AND BRAIN METABOLITE CONCENTRATIONS IN ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 Univ Calif San Francisco, Ctr Imaging Neurodegenerat Dis, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. Univ New Mexico, Mind Res Network, Albuquerque, NM 87131 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2011 VL 35 IS 6 SU S BP 134A EP 134A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804300495 ER PT J AU Mon, A Durazzo, TC Hutchison, K Meyerhoff, DJ AF Mon, A. Durazzo, T. C. Hutchison, K. Meyerhoff, D. J. TI ASSOCIATIONS BETWEEN BDNF VAL66MET GENOTYPE AND REGIONAL BRAIN VOLUME CHANGES DURING EARLY RECOVERY FROM ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 Univ Calif San Francisco, Ctr Imaging Neurodegenerat Dis, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. Univ New Mexico, Mind Res Network, Albuquerque, NM 87131 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 JUN PY 2011 VL 35 IS 6 SU S BP 134A EP 134A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804300494 ER PT J AU Hawkins, EJ Malte, CA Pedersen, ER Baer, JS Kivlahan, DR AF Hawkins, E. J. Malte, C. A. Pedersen, E. R. Baer, J. S. Kivlahan, D. R. TI HEALTH CARE COSTS AMONG PATIENTS USING SUBSTANCE USE DISORDER SPECIALTY-CARE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 [Hawkins, E. J.; Malte, C. A.; Baer, J. S.; Kivlahan, D. R.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Hawkins, E. J.; Pedersen, E. R.; Baer, J. S.; Kivlahan, D. R.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 JUN PY 2011 VL 35 IS 6 SU S BP 203A EP 203A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804301265 ER PT J AU Gubner, NR McKinnon, CS Phillips, TJ AF Gubner, N. R. McKinnon, C. S. Phillips, T. J. TI INTERACTIONS BETWEEN NICOTINE AND ETHANOL ON LOCOMOTOR ACTIVITY IN DBA/2J MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 [Gubner, N. R.; McKinnon, C. S.; Phillips, T. J.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland Alcohol Res Ctr, Dept Behav Neurosci, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 JUN PY 2011 VL 35 IS 6 SU S BP 240A EP 240A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804301412 ER PT J AU Rasmussen, DD Strand, LE Kincaid, CL Froehlich, JC AF Rasmussen, D. D. Strand, L. E. Kincaid, C. L. Froehlich, J. C. TI [PRAZOSIN plus PROPRANOLOL] REDUCES ALCOHOL DRINKING IN ALCOHOL-PREFERRING (P) RATS MORE EFFECTIVELY THAN EITHER DRUG ALONE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 VA Puget Sound Hlth Care Syst, Educ & Clin Ctr, VISN Mental Illness Res 20, Seattle, WA 98195 USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 1 Z9 1 U1 0 U2 6 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 JUN PY 2011 VL 35 IS 6 SU S BP 249A EP 249A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804301450 ER PT J AU Rasmussen, DD Strand, LE Kincaid, CL AF Rasmussen, D. D. Strand, L. E. Kincaid, C. L. TI THE alpha 1-ADRENERGIC RECEPTOR ANTAGONIST, DOXAZOSIN, REDUCES ALCOHOL DRINKING IN ALCOHOL-PREFERRING (P) RATS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr 20, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2011 VL 35 IS 6 SU S BP 250A EP 250A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804301451 ER PT J AU Cingolani, E Lepor, NE Singh, BN AF Cingolani, Eugenio Lepor, Norman E. Singh, Bramah N. TI The Electrophysiological Properties of Ranolazine: A Metabolic Anti-Ischemic Drug or an Energy-Efficient Antiarrhythmic Agent? SO REVIEWS IN CARDIOVASCULAR MEDICINE LA English DT Review DE Ranolazine; Anti-ischemic agents; Mechanisms of arrhythmias ID FATTY-ACID OXIDATION; SENSITIVE POTASSIUM CHANNELS; RANDOMIZED CONTROLLED-TRIAL; STRESS-INDUCED APOPTOSIS; ACUTE CORONARY SYNDROMES; ATRIAL-FIBRILLATION; ANTIANGINAL AGENT; CARDIOVASCULAR EVENTS; VENTRICULAR MYOCYTES; GLUCOSE-OXIDATION AB Ranolazine, a newer anti-ischemic agent that appears to induce a more efficient utilization of adenosine triphosphate at the cellular level, has been shown to be clinically beneficial in patients with chronic stable angina. More recently, the antiarrhythmic effects of the drug have been described in patients with acute coronary syndromes, as well as in those with atrial fibrillation, when combined with other agents. Experimentally, the predominant inhibitory effects on late I-Na, I-Ca, INa-Ca, and I-Ks with little or no effect on I-to or I-K1, have been demonstrated. Different experimental models have shown the potential beneficial effect of the drug in both supraventricular and ventricular arrhythmias. Interestingly, despite its potential prolongation of the QT interval, ranolazine does not appear to induce ventricular arrhythmias in animal models. Whether the antiarrhythmic effect is secondary to a more efficient energy production by the cardiac cell or by its direct effect on ion channels is still unclear. The effect of ranolazine on other ionic currents, as well as its potential as a clinically relevant antiarrhythmic agent, still needs to be studied. [Rev Cardioyasc Med. 2011;12(3):136-142 doi: 10.3909/ricm0572] (C) 2011 MedReviews (R), LLC C1 [Cingolani, Eugenio; Lepor, Norman E.] Cedars Sinai Med Ctr, Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA. [Singh, Bramah N.] Vet Adm Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA USA. RP Cingolani, E (reprint author), Cedars Sinai Med Ctr, Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA. NR 45 TC 2 Z9 2 U1 0 U2 0 PU MEDREVIEWS, LLC PI NEW YORK PA 1370 BROADWAY, STE 900, NEW YORK, NY 10018 USA SN 1530-6550 J9 REV CARDIOVASC MED JI Rev. Cardiovasc. Med. PD SUM PY 2011 VL 12 IS 3 BP 136 EP 142 DI 10.3909/ricm0572 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 838PU UT WOS:000296305500004 PM 22080924 ER PT J AU Metra, M O'Connor, CM Davison, BA Cleland, JGF Ponikowski, P Teerlink, JR Voors, AA Givertz, MM Mansoor, GA Bloomfield, DM Jia, G DeLucca, P Massie, B Dittrich, H Cotter, G AF Metra, Marco O'Connor, Christopher M. Davison, Beth A. Cleland, John G. F. Ponikowski, Piotr Teerlink, John R. Voors, Adriaan A. Givertz, Michael M. Mansoor, George A. Bloomfield, Daniel M. Jia, Gang DeLucca, Paul Massie, Barry Dittrich, Howard Cotter, Gad TI Early dyspnoea relief in acute heart failure: prevalence, association with mortality, and effect of rolofylline in the PROTECT Study SO EUROPEAN HEART JOURNAL LA English DT Article DE Acute heart failure; Dyspnoea; Diuretics ID WORSENING RENAL-FUNCTION; RANDOMIZED CONTROLLED-TRIALS; A(1) RECEPTOR ANTAGONIST; INTENSIVE-CARE MEDICINE; IN-HOSPITAL MORTALITY; EUROPEAN-SOCIETY; CLINICAL-TRIALS; OF-CARDIOLOGY; TASK-FORCE; END-POINTS AB Aims Dyspnoea and pulmonary and/or peripheral congestion are the most frequent manifestations of acute heart failure (AHF) and are important targets for therapy. We have assessed changes in dyspnoea, their relationship with mortality, and the effects of the adenosine A1 receptor antagonist rolofylline on these endpoints in patients enrolled in the PROTECT trial. Methods and results PROTECT was a prospective, double-blind, placebo-controlled study assessing the effect of rolofylline in patients hospitalized for AHF with dyspnoea, fluid overload, increased plasma natriuretic peptides, and mild-to-moderate renal dysfunction. Early dyspnoea relief, prospectively defined as moderately or markedly better dyspnoea at both 24 and 48 h after the start of study drug administration, occurred in 49.8% of the patients. Early dyspnoea relief was associated with greater weight loss and with reduced mortality at Days 14 and 30 [hazard ratio (HR) 0.28, 95% confidence interval (CI): 0.15, 0.50; and 0.35, 95% CI: 0.22, 0.55, respectively]. Rolofylline administration was associated with an increase in the proportion of patients showing early dyspnoea relief (HR 1.30; 95% CI: 1.08, 1.57) and with a numerically lower mortality at 14 and 30 days, largely driven by the mortality due to HF [at 30 days, HR (95% CI, P-value): 0.65 (0.38-1.10, P = 0.107)]. Rolofylline did not reduce episodes of in-hospital worsening HF or post-discharge re-admissions, nor did it improve survival at 60 or 180 days. Conclusion The present analysis from PROTECT demonstrated that more weight loss was associated with early dyspnoea relief and reduced short-term mortality. C1 [Metra, Marco] Univ Brescia, Dept Expt & Appl Med, Brescia, Italy. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC USA. [Davison, Beth A.; Cotter, Gad] Momentum Res Inc, Durham, NC USA. [Cleland, John G. F.] Univ Hull, Kingston Upon Hull, Yorks, England. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Teerlink, John R.; Massie, Barry] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.; Massie, Barry] San Francisco VA Med Ctr, San Francisco, CA USA. [Voors, Adriaan A.] Univ Groningen, Groningen, Netherlands. [Givertz, Michael M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mansoor, George A.; Bloomfield, Daniel M.] Merck Res Labs, Rahway, NJ USA. [Jia, Gang; DeLucca, Paul] Merck Res Labs, N Wales, PA USA. [Dittrich, Howard] Novacardia Inc, San Diego, CA USA. RP Metra, M (reprint author), Univ Brescia, Dept Expt & Appl Med, Brescia, Italy. EM metramarco@libero.it RI Teerlink, John/D-2986-2012; Ponikowski, Piotr/O-6454-2015 OI 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 NovaCardia, Inc.; Merck FX This study was funded by NovaCardia, Inc. As of September 2007, NovaCardia is a wholly owned subsidiary of Merck & Co., Inc.; M. M., C.M.O C., J.G.F.C., P. P., J.R.T, A. A. V, M. M. G., B. M., B. A. D., and G. C. have received honoraria and/or research funding from Merck and/or served as consultants to Merck. H. D. has ownership in NovaCardia, and has served as a consultant to Merck. G.J., G. A. M., D. M. B, and P. D. are employees of Merck. NR 36 TC 50 Z9 50 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JUN PY 2011 VL 32 IS 12 BP 1519 EP 1534 DI 10.1093/eurheartj/ehr042 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 830TC UT WOS:000295679100018 PM 21388992 ER PT J AU Resick, LK Leonardo, ME McGinnis, KA Stewart, J Goss, C Ellison, TM AF Resick, Lenore K. Leonardo, Maureen E. McGinnis, Kathleen A. Stewart, Jennifer Goss, Cari Ellison, Tammy M. TI A Retrospective Data Analysis of Two Academic Nurse-Managed Wellness Center Sites SO JOURNAL OF GERONTOLOGICAL NURSING LA English DT Article ID OLDER-ADULTS; CARE AB The purpose of this study was to describe the trends, themes, and outcomes of interventions over time within and between two academic nurse-managed wellness center (NMWC) sites. Documentation of wellness interventions and outcomes of these interventions presented ongoing challenges. The Omaha System was used as a documentation system to capture both interventions and client outcomes. A retrospective chart analysis revealed that the most commonly reported problems were circulation and nutrition. Interventions focused on teaching, guidance, and counseling; subsequently, the outcomes of knowledge, behavior, and status increased modestly with time for the older adult clients who attended these NMWC sites. C1 [Resick, Lenore K.; Ellison, Tammy M.] Duquesne Univ, Sch Nursing, Pittsburgh, PA 15282 USA. [Resick, Lenore K.; Leonardo, Maureen E.] Nurse Managed Wellness Ctr, Pittsburgh, PA USA. [Resick, Lenore K.] MSN Program, Pittsburgh, PA USA. [Stewart, Jennifer; Goss, Cari] Natl Nursing Ctr Consortium, Pittsburgh, PA USA. [McGinnis, Kathleen A.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Resick, LK (reprint author), Duquesne Univ, Sch Nursing, 311 Fisher Hall,600 Forbes Ave, Pittsburgh, PA 15282 USA. EM resick@duq.edu FU Duquesne University FX The authors disclose that they have no significant financial interests in any product or class of products discussed directly or indirectly in this activity. This project was funded by a Duquesne University Faculty Development Grant. 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. NR 22 TC 3 Z9 3 U1 0 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0098-9134 J9 J GERONTOL NURS JI J. Gerontol. Nurs. PD JUN PY 2011 VL 37 IS 6 BP 42 EP 52 DI 10.3928/00989134-20110302-02 PG 11 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA 811XF UT WOS:000294251000007 PM 21417196 ER PT J AU Bearden, CE Shih, VH Green, MF Gitlin, M Sokolski, KN Levander, E Marusak, S Hammen, C Sugar, CA Altshuler, LL AF Bearden, Carrie E. Shih, Vivian H. Green, Michael F. Gitlin, Michael Sokolski, Kenneth N. Levander, Eric Marusak, Susan Hammen, Constance Sugar, Catherine A. Altshuler, Lori L. TI The impact of neurocognitive impairment on occupational recovery of clinically stable patients with bipolar disorder: a prospective study SO BIPOLAR DISORDERS LA English DT Article DE attention; episodic memory; euthymic; executive function; functional outcome; processing speed; recovery; subsyndromal depression; vocational; working memory ID SUBSYNDROMAL DEPRESSIVE SYMPTOMS; I DISORDER; FUNCTIONAL IMPAIRMENT; COGNITIVE IMPAIRMENT; RATING-SCALE; FOLLOW-UP; SCHIZOPHRENIA; DISABILITY; MANIA; HOSPITALIZATION AB Objective: Many patients with bipolar disorder do not regain their premorbid level of occupational functioning even after mood episodes have resolved. The reasons for this are not well understood. We evaluated the relationship between neurocognition and occupational function in bipolar disorder patients, following symptomatic recovery. Methods: A total of 79 previously employed adults with bipolar I disorder who achieved symptomatic recovery (i.e., at least six weeks clinically euthymic) following a manic episode underwent a neurocognitive evaluation and assessment of occupational functioning. Study participants were evaluated every three months thereafter for up to nine months. Factor analysis was applied to reduce the initial set of neurocognitive variables to five domains: episodic memory, working memory/attention, executive function, visual scanning, and speed of processing. Multiple logistic regression models were used to examine the joint predictive values of these domains for determining occupational recovery. Results: At the time of symptomatic recovery, four of five neurocognitive factors were significant predictors of concomitant occupational recovery and the fifth, executive function, showed a trend in the same direction. For those not occupationally recovered at baseline, longitudinal analyses revealed that changes between baseline and the three-month follow-up timepoint in most cognitive domains were robust and highly significant predictors of occupational recovery at three months. Conclusions: These findings indicate that better neurocognitive function in multiple domains and improvement in these domains over time are strongly predictive of subsequent occupational recovery. Treatments that target cognitive deficit may therefore have potential for improving long-term vocational functioning in bipolar illness. C1 [Bearden, Carrie E.; Green, Michael F.; Gitlin, Michael; Levander, Eric; Marusak, Susan; Sugar, Catherine A.; Altshuler, Lori L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Bearden, Carrie E.; Hammen, Constance] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Shih, Vivian H.; Sugar, Catherine A.] UCLA Sch Publ Hlth, Dept Biostat, Los Angeles, CA USA. [Green, Michael F.; Sokolski, Kenneth N.; Marusak, Susan; Altshuler, Lori L.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Sokolski, Kenneth N.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. RP Bearden, CE (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, David Geffen Sch Med, 300 Bldg Med Plaza,Suite 2265, Los Angeles, CA 90095 USA. EM cbearden@mednet.ucla.edu FU National Institute of Mental Health [5R01MH057762, RL1DA024853, K23MH74644]; Abbott Laboratories at the UCLA laboratory FX Funding for this study was provided by grants 5R01MH057762 (LLA), RL1DA024853 (LLA, CEB), and K23MH74644 (CEB) from the National Institute of Mental Health. Additionally, Abbott Laboratories provided funding to obtain divalproex sodium levels at the UCLA laboratory and provided divalproex sodium for some study subjects (LLA). NR 54 TC 37 Z9 37 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2011 VL 13 IS 4 BP 323 EP 333 DI 10.1111/j.1399-5618.2011.00928.x PG 11 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 807QK UT WOS:000293914600001 PM 21843272 ER PT J AU Ghosh, A Malaisrie, N Leahy, KP Singhal, S Einhorn, E Howlett, P Cohen, NA Mirza, N AF Ghosh, Ankona Malaisrie, Nora Leahy, Kevin P. Singhal, Sunil Einhorn, Eugene Howlett, Paul Cohen, Noam A. Mirza, Natasha TI Cellular Adaptive Inflammation Mediates Airway Granulation in a Murine Model of Subglottic Stenosis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE subglottic stenosis; granulation tissue; murine model; orthotopic transplantation; airway epithelial injury ID OBLITERATIVE BRONCHIOLITIS; RAT MODEL; TRANSPLANTATION; SECRETIONS; EPITHELIUM; REJECTION; INJURY AB Objective. To determine the contribution of B- and T-cell-mediated inflammation in a murine airway granulation model. Study Design. Pilot study in a modified murine model. Setting. Philadelphia VA Medical Center Research Building. Subjects and Methods. Laryngotracheal complexes (LTCs) from 54 donor C57BL/6 mice were harvested and divided into 3 groups: (1) uninjured, (2) mechanically injured using a wire brush, and (3) chemically injured using hydrochloric acid. One donor LTC from each group was placed in deep dorsal subcutaneous pockets of either severe combined immunodeficiency (SCID)- or C57BL-recipient mice, for a total of 3 transplanted tracheas per recipient mouse. After 3 weeks, the transplanted LTCs were harvested from both C57BL- and SCID-recipient mice. Tissues were fixed, sectioned, and stained with hematoxylin and eosin. Representative slides were reviewed by a blinded pathologist to determine the formation of granulation tissue and graded as to the degree of formation of granulation tissue. Results. Despite significant granulation formation in C57BL-recipient mice, direct airway injury did not induce the formation of granulation tissue under the disrupted epithelium of airway mucosa in SCID mice 3 weeks after injury. Conclusion. The data indicate that the immune response that results in the formation of granulation tissue is mediated by circulating B-and/or T-cell processes rather than resident airway immune cells. Further studies focusing on cellular adaptive immune processes in response to airway injury may provide a novel treatment modality for subglottic stenosis. C1 [Ghosh, Ankona; Malaisrie, Nora; Leahy, Kevin P.; Cohen, Noam A.; Mirza, Natasha] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Singhal, Sunil] Philadelphia VA Med Ctr, Dept Thorac Surg, Philadelphia, PA USA. [Einhorn, Eugene; Howlett, Paul] Philadelphia VA Med Ctr, Dept Pathol, Philadelphia, PA USA. RP Ghosh, A (reprint author), Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, 3400 Spruce St,5 Silverstein, Philadelphia, PA 19104 USA. EM ankonag@mail.med.upenn.edu OI Cohen, Noam/0000-0002-9462-3932 FU Hospital of the University of Pennsylvania, Department of Otorhinolaryngology: Head and Neck Surgery FX Hospital of the University of Pennsylvania, Department of Otorhinolaryngology: Head and Neck Surgery. NR 17 TC 8 Z9 8 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUN PY 2011 VL 144 IS 6 BP 927 EP 933 DI 10.1177/0194599810397750 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 808SN UT WOS:000293998800019 PM 21493347 ER PT J AU Sher, L AF Sher, Leo TI Towards a model of suicidal behavior among physicians SO REVISTA BRASILEIRA DE PSIQUIATRIA LA English DT Editorial Material ID IDEATION C1 James J Peters Vet Adm Med Ctr, Dept Psychiat, Mt Sinai Sch Med, New York, NY USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, Dept Psychiat, Mt Sinai Sch Med, New York, NY USA. NR 6 TC 1 Z9 1 U1 1 U2 2 PU ASSOC BRASILEIRA PSIQUIATRIA PI SAO PAULO PA SUBSCRIPTION DEPARTMENT, RUA PEDRO DE TOLEDO, 967 - CASA 01, SAO PAULO, SP 04039-032 A, BRAZIL SN 1516-4446 J9 REV BRAS PSIQUIATR JI Rev. Bras. Psiquiatr. PD JUN PY 2011 VL 33 IS 2 BP 111 EP 112 PG 2 WC Psychiatry SC Psychiatry GA 804KN UT WOS:000293652800002 PM 21829900 ER PT J AU Curtis, JR Singh, JA AF Curtis, Jeffrey R. Singh, Jasvinder A. TI Use of Biologics in Rheumatoid Arthritis: Current and Emerging Paradigms of Care SO CLINICAL THERAPEUTICS LA English DT Review DE biologic therapy; disease progression; effectiveness; physical function; quality of life; rheumatoid arthritis ID ANTITUMOR-NECROSIS-FACTOR; MODIFYING ANTIRHEUMATIC DRUGS; CLINICAL-DISEASE ACTIVITY; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; RECEIVING CONCOMITANT METHOTREXATE; INTERLEUKIN-1 RECEPTOR ANTAGONIST; SERIOUS BACTERIAL-INFECTIONS; RANDOMIZED CONTROLLED-TRIALS; ALPHA MONOCLONAL-ANTIBODY; PLACEBO-CONTROLLED TRIAL AB Background: Improved understanding of rheumatoid arthritis (RA) pathogenesis has led to the development of new biologic treatments that target specific elements of RA inflammatory response. Objective: Our aim was to provide a comprehensive review of biologic therapies currently used for the treatment of RA. Methods: A search of MEDLINE (up to October 2010) was conducted. Preference for article inclusion was given to English language meta-analyses and large, Phase III, randomized controlled trials (RCTs) of biologic treatments in patients with RA. Results: In large RCTs, significantly more patients treated with tumor necrosis factor-alpha (TNF-alpha) antagonists (as monotherapy, or as an adjunct to methotrexate) versus controls (35%-67% vs 9%-33% of patients; P <= 0.01) achieved an American College of Rheumatology 20 response as a primary study end point. However, safety concerns especially the potential for serious infections and malignancy remain for TNF-alpha blockade. For example, 1 meta-analysis (>5000 patients) reported a 2-fold increase (95% CI, 1.3-3.1) in the risk of serious infections and a 3.3-fold increase (95% CI, 1.2-9.1) in the risk of malignancy. Abatacept and rituximab (given in combination with methotrexate) may be useful clinical alternatives for RA patients with an inadequate response to TNF-alpha antagonists. These agents do not appear to increase the risk of serious infections (OR, 1.35-1.45; 95% CI, 0.56-3.73), although rituximab may rarely cause progressive multifocal leukoencephalopathy (0.4 cases per 100,000 hospitalizations). Conclusions: Over the last decade, targeted biologic agents have transformed RA treatment. Although relatively expensive in the short term, the direct costs of these biologics may be offset by slowed disease progression and significant improvements in RA symptoms, physical function, and quality of life. (Clin Ther. 2011;33:679-707) (C) 2011 Elsevier HS Journals, Inc. All rights reserved. C1 [Curtis, Jeffrey R.] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Arthrit Clin Intervent Program, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Curtis, JR (reprint author), Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Arthrit Clin Intervent Program, FOT 805D,510 20th St S, Birmingham, AL 35294 USA. EM jcurtis@uab.edu OI singh, jasvinder/0000-0003-3485-0006 FU National Institutes of Health [AR 053351]; Arthritis Foundation; Roche; Roche/Genentech; Novartis; CORRONA; Amgen; Pfizer; Centocor; UCB; Takeda; Savient; Wyeth; URL pharmaceuticals FX Dr. Curtis has received support from the National Institutes of Health (AR 053351) and the Arthritis Foundation. This work was supported in part by Roche and developed independently of Roche. Editorial support was provided by Sara Duggan, PhD, and Maribeth Bogush, PhD.; Dr. Curtis has received research grants and/or consulting fees from Roche/Genentech, Novartis, CORRONA, Amgen, Pfizer, Centocor, and UCB. Dr. Singh has received speaker honoraria from Abbott; research and travel grants from Takeda, Savient, Wyeth, and Amgen; and consultant fees from Savient and URL pharmaceuticals. NR 114 TC 43 Z9 44 U1 2 U2 8 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD JUN PY 2011 VL 33 IS 6 BP 679 EP 707 DI 10.1016/j.clinthera.2011.05.044 PG 29 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 793AO UT WOS:000292793000002 PM 21704234 ER PT J AU Cadena, J Prigmore, T Bowling, J Ayala, BA Kirkman, L Parekh, A Scepanski, T Patterson, JE AF Cadena, Jose Prigmore, Teresa Bowling, Jason Ayala, Beth Ann Kirkman, Leni Parekh, Amruta Scepanski, Theresa Patterson, Jan E. TI Improving Influenza Vaccination of Healthcare Workers by Means of Quality Improvement Tools SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article AB For a healthcare worker seasonal influenza vaccination quality improvement project, interventions included support of leadership, distribution of vaccine kits, grand rounds, an influenza website, a screensaver, e-mails, phone messages, and audit feedback. Vaccination rates increased from 58.8% to 76.6% (P < .01). Quality improvement increased the voluntary vaccination rate but did not achieve a rate more than 80%. Infect Control Hosp Epidemiol 2011;32(6):616-618 C1 [Cadena, Jose; Bowling, Jason; Patterson, Jan E.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Cadena, Jose; Bowling, Jason; Parekh, Amruta; Patterson, Jan E.] Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA. [Prigmore, Teresa; Ayala, Beth Ann; Kirkman, Leni; Scepanski, Theresa] Univ Hlth Syst, San Antonio, TX USA. RP Cadena, J (reprint author), Mail Code 7881,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM cadenazuluag@uthscsa.edu NR 10 TC 9 Z9 9 U1 2 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUN PY 2011 VL 32 IS 6 BP 616 EP 618 DI 10.1086/660198 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 791GQ UT WOS:000292653500013 PM 21558776 ER PT J AU Sher, L Yehuda, R AF Sher, Leo Yehuda, Rachel TI Preventing Suicide Among Returning Combat Veterans: A Moral Imperative SO MILITARY MEDICINE LA English DT Editorial Material ID MENTAL-DISORDERS; HEALTH; RISK C1 [Sher, Leo; Yehuda, Rachel] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. [Sher, Leo; Yehuda, Rachel] Mt Sinai Sch Med, New York, NY USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 9 TC 5 Z9 5 U1 0 U2 2 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 JUN PY 2011 VL 176 IS 6 BP 601 EP 602 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 792XN UT WOS:000292783800003 PM 21702372 ER PT J AU Rosenthal, JZ Grosswald, S Ross, R Rosenthal, N AF Rosenthal, Joshua Z. Grosswald, Sarina Ross, Richard Rosenthal, Norman TI Effects of Transcendental Meditation in Veterans of Operation Enduring Freedom and Operation Iraqi Freedom With Posttraumatic Stress Disorder: A Pilot Study SO MILITARY MEDICINE LA English DT Article ID MENTAL-HEALTH; PTSD; AFGHANISTAN; SOLDIERS; REST AB We conducted an uncontrolled pilot study to determine whether transcendental meditation (TM) might be helpful in treating veterans from Operation Enduring Freedom or Operation Iraqi Freedom with combat-related posttraumatic stress disorder (PTSD). Five veterans were trained in the technique and followed for 12 weeks. All subjects improved on the primary outcome measure, the Clinician Administered PTSD Scale (mean change score, 31.4; p = 0.02; df = 4). Significant improvements were also observed for 3 secondary outcome measures: Clinician's Global Inventory-Severity (mean change score, 1.60; p < 0.04; df = 4), Quality of Life Enjoyment and Satisfaction Questionnaire (mean change score, -13.00; p < 0.01; df = 4), and the PTSD Checklist-Military Version (mean change score, 24.00; p < 0.02; df = 4). TM may have helped to alleviate symptoms of PTSD and improve quality of life in this small group of veterans. Larger, placebo-controlled studies should be undertaken to further determine the efficacy of TM in this population. C1 [Rosenthal, Joshua Z.; Rosenthal, Norman] Capital Clin Res Associates, Rockville, MD 20852 USA. [Grosswald, Sarina] Inst Nat Med & Prevent, Fairfield, IA 52557 USA. [Ross, Richard] Vet Affairs Med Ctr, Behav Hlth Serv HMC 116, Philadelphia, PA 19104 USA. RP Rosenthal, JZ (reprint author), Capital Clin Res Associates, 5515 Secur Lane,Suite 525, Rockville, MD 20852 USA. RI Schueter, nicos/A-3625-2014 FU Dalio Family Foundation; Center for Environmental Therapeutics FX Financial support was provided by the Dalio Family Foundation and Center for Environmental Therapeutics. NR 29 TC 31 Z9 31 U1 10 U2 26 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 JUN PY 2011 VL 176 IS 6 BP 626 EP 630 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 792XN UT WOS:000292783800009 PM 21702378 ER PT J AU Medina, MT Aguilar-Estrada, RL Alvarez, A Duron, RM Martinez, L Dubon, S Estrada, AL Zuniga, C Cartagena, D Thompson, A Ramirez, E Banegas, L Osorio, JR Delgado-Escueta, AV Collins, JS Holden, KR AF Medina, Marco T. Aguilar-Estrada, Rafael L. Alvarez, Allan Duron, Reyna M. Martinez, Lizandro Dubon, Sofia Estrada, Ana L. Zuniga, Concepcion Cartagena, Dora Thompson, Arnold Ramirez, Eunice Banegas, Lenin Osorio, Juan R. Delgado-Escueta, Antonio V. Collins, Julianne S. Holden, Kenton R. TI Reduction in rate of epilepsy from neurocysticercosis by community interventions: The Salama, Honduras Study SO EPILEPSIA LA English DT Article DE Epilepsy; Incidence; Epidemiology; Neurocysticercosis; Honduras; Community; Interventions ID TO-DOOR SURVEY; CEREBRAL CYSTICERCOSIS; RURAL BOLIVIA; PREVALENCE; EPIDEMIOLOGY; SEIZURES; PERU; AMERICA; TRIAL AB Purpose: Epilepsy is highly prevalent in developing countries like Honduras, with few studies evaluating this finding. This population-based study evaluated the impact of an 8-year public health and educational intervention program in reducing symptomatic epilepsies in rural Salama, Honduras. Methods: We used the capture and recapture method including review of charts, previous databases, key informants from the community, and a second house-to-house survey for epilepsy. Epilepsy incidence and prevalence day after the interventions was May 5, 2005. Residents with active epilepsy with onset after May 1997 were offered neurologic evaluation, electroencephalography, and brain tomography. New data over 8 years were compared to preintervention data from the initial baseline 1997 study utilizing prevalence ratios and confidence intervals. Other calculations utilized chi square or Fisher's exact tests. Key Findings: Thirty-three of 36 patients with onset of active epilepsy after 1997 accepted evaluations to determine etiology. Symptomatic etiology was found in 58.3%. Neurocysticercosis (NCC) was again the most frequent cause (13.9%), followed by perinatal insults (11.1%). Epilepsy secondary to NCC was significantly reduced from 36.9% in 1997 (p = 0.02). The incidence (35.7/100,000) and prevalence (11.8/1,000) of active epilepsy were not significantly reduced when compared to the incidence (92.7/100,000) and prevalence (15.4/1,000) of active epilepsy in 1997. Significance: Our cohort appears to indicate that health and educational community interventions can reduce preventable epilepsy from NCC in a hyperendemic population in a low-resource, developing country. Plans are underway for the Honduran Government to institute this rural model countrywide. C1 [Medina, Marco T.; Aguilar-Estrada, Rafael L.; Alvarez, Allan; Duron, Reyna M.; Dubon, Sofia; Thompson, Arnold; Ramirez, Eunice] Natl Autonomous Univ Honduras, Neurol Training Program, Tegucigalpa, Honduras. [Martinez, Lizandro; Cartagena, Dora; Banegas, Lenin; Osorio, Juan R.] Secretary Hlth, Olancho, Honduras. [Estrada, Ana L.; Zuniga, Concepcion] Secretary Hlth, Tegucigalpa, Honduras. [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA USA. [Delgado-Escueta, Antonio V.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Collins, Julianne S.; Holden, Kenton R.] Greenwood Genet Ctr, Greenwood, SC 29646 USA. [Holden, Kenton R.] Med Univ S Carolina, Dept Neurosci Pediat Neurol, Charleston, SC 29425 USA. [Holden, Kenton R.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Medina, MT (reprint author), Inst Neurociencias, Edificio Mater Dei, Tegucigalpa, Honduras. EM marcotmedina@yahoo.com OI Delgado-Escueta, Antonio V./0000-0002-1581-6999; Duron, Reyna M./0000-0002-9425-2289 FU mayors of Salama County, Olancho, Honduras, Central America; Honduras Secretary of Health (Nutrition and Health Program); World Bank (Community Intervention); United Nations Population Fund; Japanese International Cooperation Agency; Instituto Neurociencias and the Spanish Neurological Society FX We thank Drs. Rebeca Hernandez (Neurophysiologist), Manuel Sierra (Epidemiologist), Jeaneth Bu (Neuroradiologist), as well as nurses Betty Diaz, Carlos Caballero, the community leaders, and all the allied health personnel of Health Area N. 8 located in Salama, as well as the personnel of the Mother-Child Clinic of Salama, Olancho, Honduras, Central America for their efforts. We especially thank the mayors of Salama County, Olancho, Honduras, Central America for their support and partial funding of the health interventions as well as logistic support for the researchers and transportation of patients. We thank the Honduras Secretary of Health (Nutrition and Health Program), the World Bank (Community Intervention), the United Nations Population Fund, and the Japanese International Cooperation Agency for funding the grants for the community interventions. We thank Instituto Neurociencias and the Spanish Neurological Society for funding the grant for the impact study including the EEG studies and brain CT scans for patients. We are indebted to the Honduran families who participated and without whom this study would not have been possible. NR 32 TC 17 Z9 17 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2011 VL 52 IS 6 BP 1177 EP 1185 DI 10.1111/j.1528-1167.2010.02945.x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 788QY UT WOS:000292460700021 PM 21275975 ER PT J AU Loring, DW Lowenstein, DH Barbaro, NM Fureman, BE Odenkirchen, J Jacobs, MP Austin, JK Dlugos, DJ French, JA Gaillard, WD Hermann, BP Hesdorffer, DC Roper, SN Van Cott, AC Grinnon, S Stout, A AF Loring, David W. Lowenstein, Daniel H. Barbaro, Nicholas M. Fureman, Brandy E. Odenkirchen, Joanne Jacobs, Margaret P. Austin, Joan K. Dlugos, Dennis J. French, Jacqueline A. Gaillard, William Davis Hermann, Bruce P. Hesdorffer, Dale C. Roper, Steven N. Van Cott, Anne C. Grinnon, Stacie Stout, Alexandra TI Common data elements in epilepsy research: Development and implementation of the NINDS epilepsy CDE project SO EPILEPSIA LA English DT Article DE Research; Epilepsy; National Institute of Neurological Disorders and Stroke ID HARMONIZATION; STATEMENT; TRIALS AB The Common Data Element (CDE) Project was initiated in 2006 by the National Institute of Neurological Disorders and Stroke (NINDS) to develop standards for performing funded neuroscience-related clinical research. CDEs are intended to standardize aspects of data collection; decrease study start-up time; and provide more complete, comprehensive, and equivalent data across studies within a particular disease area. Therefore, CDEs will simplify data sharing and data aggregation across NINDS-funded clinical research, and where appropriate, facilitate the development of evidenced-based guidelines and recommendations. Epilepsy-specific CDEs were established in nine content areas: (1) Antiepileptic Drugs (AEDs) and Other Antiepileptic Therapies (AETs), (2) Comorbidities, (3) Electrophysiology, (4) Imaging, (5) Neurological Exam, (6) Neuropsychology, (7) Quality of Life, (8) Seizures and Syndromes, and (9) Surgery and Pathology. CDEs were developed as a dynamic resource that will accommodate recommendations based on investigator use, new technologies, and research findings documenting emerging critical disease characteristics. The epilepsy-specific CDE initiative can be viewed as part of the larger international movement toward "harmonization'' of clinical disease characterization and outcome assessment designed to promote communication and research efforts in epilepsy. It will also provide valuable guidance for CDE improvement during further development, refinement, and implementation. This article describes the NINDS CDE Initiative, the process used in developing Epilepsy CDEs, and the benefits of CDEs for the clinical investigator and NINDS. C1 [Loring, David W.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Loring, David W.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Lowenstein, Daniel H.; Barbaro, Nicholas M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Barbaro, Nicholas M.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA. [Fureman, Brandy E.; Odenkirchen, Joanne; Jacobs, Margaret P.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Austin, Joan K.] Indiana Univ Purdue Univ, Sch Nursing, Indianapolis, IN 46202 USA. [Dlugos, Dennis J.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Dlugos, Dennis J.] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [French, Jacqueline A.] NYU, Dept Neurol, New York, NY 10016 USA. [Gaillard, William Davis] George Washington Univ, Childrens Natl Med Ctr, Ctr Neurosci, Washington, DC USA. [Hermann, Bruce P.] Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Hesdorffer, Dale C.] Columbia Univ, Dept Epidemiol, New York, NY USA. [Roper, Steven N.] Univ Florida, Dept Neurosurg, Gainesville, FL USA. [Van Cott, Anne C.] VA Pittsburgh Healthcare Syst, Div Neurol, Pittsburgh, PA USA. [Van Cott, Anne C.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Grinnon, Stacie; Stout, Alexandra] KAI Res Inc, Rockville, MD USA. RP Loring, DW (reprint author), Emory Univ, Dept Neurol, 101 Woodruff Circle,Suite 6000, Atlanta, GA 30322 USA. EM dloring@emory.edu RI shengkun, yu/B-8440-2012; French, Jacqueline/G-6795-2013 OI French, Jacqueline/0000-0003-2242-8027 FU NINDS NIH HHS [N01NS72372] NR 8 TC 43 Z9 43 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2011 VL 52 IS 6 BP 1186 EP 1191 DI 10.1111/j.1528-1167.2011.03018.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 788QY UT WOS:000292460700022 PM 21426327 ER PT J AU Zhao, XF Wenk, JF Burger, M Liu, Y Das, MK Combs, W Ge, L Guccione, JM Kassab, GS AF Zhao, Xuefeng Wenk, Jonathan F. Burger, Mike Liu, Yi Das, Mithilesh K. Combs, William Ge, Liang Guccione, Julius M. Kassab, Ghassan S. TI Simulation of Mechanical Environment in Active Lead Fixation: Effect of Fixation Helix Size SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE pacing lead; defibrillation lead; cardiac penetration; finite element analysis ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; COMPLICATIONS; PERFORATION; MYOCARDIUM; SYSTEMS AB The risk of myocardial penetration due to active-fixation screw-in type pacing leads has been reported to increase as the helix electrodes become smaller. In order to understand the contributing factors for lead penetration, we conducted finite element analyses of acute myocardial micro-damage induced by a pacemaker lead screw-in helix electrode. We compared the propensity for myocardial micro-damage of seven lead designs including a baseline model, three modified designs with various helix wire cross-sectional diameters, and three modified designs with different helix diameters. The comparisons show that electrodes with a smaller helix wire diameter cause more severe micro-damage to the myocardium in the early stage. The damage severity, represented by the volume of failed elements, is roughly the same in the middle stage, whereas in the later stage the larger helix wire diameter generally causes more severe damage. The onset of myocardial damage is not significantly affected by the helix diameter. As the helix diameter increases, however, the extent of myocardial damage increases accordingly. The present findings identified several of the major risk factors for myocardial damage whose consideration for lead use and design might improve acute and chronic lead performance. [DOI: 10.1115/1.4004288] C1 [Wenk, Jonathan F.; Ge, Liang; Guccione, Julius M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94121 USA. [Burger, Mike] Livermore Software Technology Corp, Livermore, CA 94550 USA. [Wenk, Jonathan F.; Ge, Liang; Guccione, Julius M.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Das, Mithilesh K.] Univ Indianapolis, Krannert Inst Cardiol, Roudebush VA Med Ctr, Sch Med, Indianapolis, IN 46202 USA. [Kassab, Ghassan S.] Indiana Univ Purdue Univ, Dept Biomed Engn, Dept Surg, Dept Cellular & Integrat Physiol, Indianapolis, IN 46202 USA. RP Kassab, GS (reprint author), 635 Barnhill Dr, Indianapolis, IN 46202 USA. EM gkassab@iupui.edu RI Zhao, Xuefeng/A-3260-2013 OI Zhao, Xuefeng/0000-0003-3834-9091 FU National Institutes of Health through National Heart, Lung, and Blood Institute [R01 HL084529, HL086400] FX This research is supported in part by the National Institutes of Health through National Heart, Lung, and Blood Institute Grants R01 HL084529 and HL086400. NR 15 TC 0 Z9 0 U1 0 U2 1 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD JUN PY 2011 VL 133 IS 6 AR 061006 DI 10.1115/1.4004288 PG 6 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 789KV UT WOS:000292515300006 ER PT J AU True, G Alexander, LB Richman, KA AF True, Gala Alexander, Leslie B. Richman, Kenneth A. TI MISBEHAVIORS OF FRONT-LINE RESEARCH PERSONNEL AND THE INTEGRITY OF COMMUNITY-BASED RESEARCH SO JOURNAL OF EMPIRICAL RESEARCH ON HUMAN RESEARCH ETHICS LA English DT Article DE research integrity; research misconduct; community-based research; front-line research personnel; vulnerable populations; qualitative research methods ID NATIONAL-SURVEY; SCIENTISTS; HEALTH; JUSTICE; WORKERS AB THERE HAS BEEN LITTLE EMPIRICAL research into misconduct and misbehavior among community research workers who recruit and collect data in vulnerable and marginalized health populations and are also members of those same communities. We conducted qualitative interviews with community research workers and traditional research assistants to understand the context and consequences of misbehaviors that pose a threat to research ethics and data integrity. In our sample, more community research workers acknowledged engaging in research wrongdoing than did traditional research assistants. These behaviors were most prevalent among community research workers who were not well-integrated into the research team. We suggest best practices for investigators to promote an environment that supports research integrity in research projects that employ community research workers. C1 [Richman, Kenneth A.] Massachusetts Coll Pharm & Hlth Sci, IRB Chair, Boston, MA USA. [Alexander, Leslie B.] Bryn Mawr Coll, IRB, Bryn Mawr, PA 19010 USA. [True, Gala] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP True, G (reprint author), Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, 9E,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM Jennifer.True2@va.gov FU [1RO1NR009879] FX This research was supported by 1RO1NR009879 to Leslie Alexander. We thank Kay Armstrong, Patrice Gammon, Diana Harris, Page Buck, and Taalibah Kariem-White for conducting study interviews and providing other assistance with the research. We are indebted to the organizations and investigators who facilitated our recruitment efforts, and especially to the front-line research personnel who so generously shared their experiences and perspectives with us. The reviewers' comments on an earlier draft of this manuscript are greatly appreciated. Disclaimer: The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 17 TC 19 Z9 19 U1 7 U2 22 PU UNIV CALIFORNIA PRESS PI BERKELEY PA C/O JOURNALS & DIGITAL PUBLISHING DIVISION, 2000 CENTER ST, STE 303, BERKELEY, CA 94704-1223 USA SN 1556-2646 J9 J EMPIR RES HUM RES JI J. Empir. Res. Hum. Res. Ethics PD JUN PY 2011 VL 6 IS 2 BP 3 EP 12 DI 10.1525/jer.2011.6.2.3 PG 10 WC Ethics; Medical Ethics SC Social Sciences - Other Topics; Medical Ethics GA 788CC UT WOS:000292422000002 PM 21680972 ER PT J AU Bales, JW Garringer, J Conley, YP Puccio, AM Okonkwo, DO Dixon, CE AF Bales, James W. Garringer, Julie Conley, Yvette P. Puccio, Ava M. Okonkwo, David O. Dixon, C. Edward TI ASSOCIATION BETWEEN THE PPP3CC GENE, CODING FOR THE CALCINEURIN GAMMA CATALYTIC SUBUNIT, AND SEVERITY OF TRAUMATIC BRAIN INJURY IN HUMANS SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 29th Annual National Neurotrauma Symposium CY JUL 10-13, 2011 CL Hollywood Beach, FL C1 [Bales, James W.; Garringer, Julie; Conley, Yvette P.; Puccio, Ava M.; Okonkwo, David O.; Dixon, C. Edward] Univ Pittsburgh, Pittsburgh, PA USA. [Dixon, C. Edward] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN PY 2011 VL 28 IS 6 BP A101 EP A101 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 788PT UT WOS:000292457600317 ER PT J AU Khan, M Sakakima, H Im, YB Shunmugavel, A Dhammu, TS Singh, A Singh, I AF Khan, Mushfiquddin Sakakima, Harutoshi Im, Yeong-Bin Shunmugavel, Anandakumar Dhammu, Tajinder Singh Singh, Avtar Singh, Inderjit TI S-NITROSOGLUTATHIONE REDUCES SECONDARY INJURY AND STIMULATES NEUROREPAIR FOLLOWING TRAUMATIC BRAIN INJURY IN RATS SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 29th Annual National Neurotrauma Symposium CY JUL 10-13, 2011 CL Hollywood Beach, FL C1 [Khan, Mushfiquddin; Sakakima, Harutoshi; Im, Yeong-Bin; Shunmugavel, Anandakumar; Dhammu, Tajinder Singh; Singh, Inderjit] Med Univ S Carolina, Charleston, SC 29425 USA. [Singh, Avtar] Ralph H Johnson VA Med Ctr, Charleston, SC 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 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN PY 2011 VL 28 IS 6 BP A60 EP A60 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 788PT UT WOS:000292457600194 ER PT J AU Shin, SS Bray, ER Dixon, CE AF Shin, Samuel S. Bray, Eric R. Dixon, C. Edward TI NICOTINE IMPROVES STRIATAL DOPAMINE RELEASE AND TYROSINE HYDROXYLASE ACTIVITY FOLLOWING TRAUMATIC BRAIN INJURY IN RATS SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 29th Annual National Neurotrauma Symposium CY JUL 10-13, 2011 CL Hollywood Beach, FL C1 [Shin, Samuel S.; Bray, Eric R.; Dixon, C. Edward] Univ Pittsburgh, Pittsburgh, PA USA. [Dixon, C. Edward] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 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 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN PY 2011 VL 28 IS 6 BP A105 EP A105 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 788PT UT WOS:000292457600329 ER PT J AU Yan, HQ Dixon, CE AF Yan, Hong Q. Dixon, C. Edward TI EFFECTS OF TWO CRANIOTOMY SIZES ON MOTOR AND COGNITIVE FUNCTION IN THE RAT SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 29th Annual National Neurotrauma Symposium CY JUL 10-13, 2011 CL Hollywood Beach, FL C1 [Yan, Hong Q.; Dixon, C. Edward] Univ Pittsburgh, Pittsburgh, PA USA. [Dixon, C. Edward] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 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 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN PY 2011 VL 28 IS 6 BP A104 EP A105 PG 2 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 788PT UT WOS:000292457600327 ER PT J AU Williams, AE Arzola, GM Strutt, AM Simpson, R Jankovic, J York, MK AF Williams, Amy E. Arzola, Gladys Marina Strutt, Adriana M. Simpson, Richard Jankovic, Joseph York, Michele K. TI Cognitive outcome and reliable change indices two years following bilateral subthalamic nucleus deep brain stimulation SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; Deep brain stimulation; Neuropsychology; Cognition; Reliable change ID ADVANCED PARKINSONS-DISEASE; TERM; MULTICENTER; MODULATION; TRIAL; LIFE AB Subthalamic nucleus deep brain stimulation (STN-DBS) is currently the treatment of choice for medication-resistant levodopa-related motor complications in patients with Parkinson's disease (PD). While STN-DBS often results in meaningful motor improvements, consensus regarding long-term neuropsychological outcome continues to be debated. We assessed the cognitive outcomes of 19 STN-DBS patients compared to a group of 18 medically-managed PD patients on a comprehensive neuropsychological battery at baseline and two years post-surgery. Patients did not demonstrate changes in global cognitive functioning on screening measures. However, neuropsychological results revealed impairments in nonverbal recall, oral information processing speed, and lexical and semantic fluency in STN-DBS patients compared to PD controls 2 years post-surgery in these preliminary analyses. Additionally, reliable change indices revealed that approximately 50% of STN-DBS patients demonstrated significant declines in nonverbal memory and oral information processing speed compared to 25-30% of PD controls, and 26% of STN-DBS patients declined on lexical fluency compared to 11% of PD patients. Approximately 30% of both groups declined on semantic fluency. The number of STN-DBS patients who converted to dementia 2 years following surgery was not significantly different from the PD participants (32% versus 16%, respectively). Our results suggest that neuropsychological evaluations may identify possible mild cognitive changes following surgery. Published by Elsevier Ltd. C1 [Williams, Amy E.; Arzola, Gladys Marina; Strutt, Adriana M.; Jankovic, Joseph; York, Michele K.] Baylor Coll Med, Dept Neurol, Parkinsons Dis & Movement Disorders Ctr, Houston, TX 77030 USA. [Simpson, Richard] Methodist Hosp, Neurol Inst, Houston, TX 77030 USA. [York, Michele K.] Parkinsons Dis Res Educ & Clin Ctr, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP York, MK (reprint author), Baylor Coll Med, Dept Neurol, Parkinsons Dis & Movement Disorders Ctr, 6501 Fannin,NB302, Houston, TX 77030 USA. EM myork@bcm.edu FU NIH/NINDS; Department of Veterans Affairs FX This material is the result of work funded by a NIH/NINDS K23 grant (PI: M.K. York) and supported with resources from the Department of Veterans Affairs, Michael E. DeBakey Veteran's Affairs Hospital, Houston, Texas. The authors wish to thank the National Parkinson's Foundation and the Parkinson's disease patients who willingly gave of their time to participate in this research project. NR 30 TC 25 Z9 26 U1 1 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD JUN PY 2011 VL 17 IS 5 BP 321 EP 327 DI 10.1016/j.parkreldis.2011.01.011 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 789BB UT WOS:000292487200004 PM 21316292 ER PT J AU Smith, EN Koller, DL Panganiban, C Szelinger, S Zhang, P Badner, JA Barrett, TB Berrettini, WH Bloss, CS Byerley, W Coryell, W Edenberg, HJ Foroud, T Gershon, ES Greenwood, TA Guo, Y Hipolito, M Keating, BJ Lawson, WB Liu, C Mahon, PB McInnis, MG McMahon, FJ McKinney, R Murray, SS Nievergelt, CM Nurnberger, JI Nwulia, EA Potash, JB Rice, J Schulze, TG Scheftner, WA Shilling, PD Zandi, PP Zollner, S Craig, DW Schork, NJ Kelsoe, JR AF Smith, Erin N. Koller, Daniel L. Panganiban, Corrie Szelinger, Szabolcs Zhang, Peng Badner, Judith A. Barrett, Thomas B. Berrettini, Wade H. Bloss, Cinnamon S. Byerley, William Coryell, William Edenberg, Howard J. Foroud, Tatiana Gershon, Elliot S. Greenwood, Tiffany A. Guo, Yiran Hipolito, Maria Keating, Brendan J. Lawson, William B. Liu, Chunyu Mahon, Pamela B. McInnis, Melvin G. McMahon, Francis J. McKinney, Rebecca Murray, Sarah S. Nievergelt, Caroline M. Nurnberger, John I., Jr. Nwulia, Evaristus A. Potash, James B. Rice, John Schulze, Thomas G. Scheftner, William A. Shilling, Paul D. Zandi, Peter P. Zoellner, Sebastian Craig, David W. Schork, Nicholas J. Kelsoe, John R. TI Genome-Wide Association of Bipolar Disorder Suggests an Enrichment of Replicable Associations in Regions near Genes SO PLOS GENETICS LA English DT Article ID 7 COMMON DISEASES; POWER ANALYSIS; RISK; METAANALYSIS; INDIVIDUALS; ANK3 AB Although a highly heritable and disabling disease, bipolar disorder's (BD) genetic variants have been challenging to identify. We present new genotype data for 1,190 cases and 401 controls and perform a genome-wide association study including additional samples for a total of 2,191 cases and 1,434 controls. We do not detect genome-wide significant associations for individual loci; however, across all SNPs, we show an association between the power to detect effects calculated from a previous genome-wide association study and evidence for replication (P = 1.5 x 10(-7)). To demonstrate that this result is not likely to be a false positive, we analyze replication rates in a large meta-analysis of height and show that, in a large enough study, associations replicate as a function of power, approaching a linear relationship. Within BD, SNPs near exons exhibit a greater probability of replication, supporting an enrichment of reproducible associations near functional regions of genes. These results indicate that there is likely common genetic variation associated with BD near exons (+/- 10 kb) that could be identified in larger studies and, further, provide a framework for assessing the potential for replication when combining results from multiple studies. C1 [Smith, Erin N.; Bloss, Cinnamon S.; Murray, Sarah S.; Schork, Nicholas J.] Scripps Genom Med & Scripps Translat Sci Inst, La Jolla, CA USA. [Smith, Erin N.] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA. [Smith, Erin N.] Univ Calif San Diego, Sch Med, Radys Childrens Hosp, La Jolla, CA 92093 USA. [Smith, Erin N.; Bloss, Cinnamon S.; Murray, Sarah S.] Scripps Hlth, La Jolla, CA USA. [Koller, Daniel L.; Edenberg, Howard J.; Foroud, Tatiana] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA. [Panganiban, Corrie; Szelinger, Szabolcs; Craig, David W.] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA. [Zhang, Peng; McInnis, Melvin G.; Zoellner, Sebastian] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Badner, Judith A.; Gershon, Elliot S.; Liu, Chunyu] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [Barrett, Thomas B.] Portland VA Med Ctr, Dept Psychiat, Portland, OR USA. [Berrettini, Wade H.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Byerley, William] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Coryell, William] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Edenberg, Howard J.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA. [Greenwood, Tiffany A.; McKinney, Rebecca; Nievergelt, Caroline M.; Shilling, Paul D.; Kelsoe, John R.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Guo, Yiran] Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Genon, Philadelphia, PA 19104 USA. [Guo, Yiran] Beijing Genom Inst Shenzhen, Shenzhen, Peoples R China. [Hipolito, Maria; Lawson, William B.; Nwulia, Evaristus A.] Howard Univ, Dept Psychiat, Washington, DC 20059 USA. [Keating, Brendan J.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Keating, Brendan J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Mahon, Pamela B.; Potash, James B.; Zandi, Peter P.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA. [McMahon, Francis J.; Schulze, Thomas G.] NIMH, Mood & Anxiety Sect, Human Genet Branch, Intramural Res Program,NIH,US Dept Hlth & Human S, Bethesda, MD 20892 USA. [Nurnberger, John I., Jr.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA. [Rice, John] Washington Univ, Div Biostat, St Louis, MO USA. [Schulze, Thomas G.] Univ Gottingen, Dept Psychiat & Psychotherapy, Gottingen, Germany. [Scheftner, William A.] Rush Univ, Dept Psychiat, Chicago, IL 60612 USA. [Schork, Nicholas J.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. [Kelsoe, John R.] VA San Diego Healthcare Syst, Dept Psychiat, La Jolla, CA USA. RP Smith, EN (reprint author), Scripps Genom Med & Scripps Translat Sci Inst, La Jolla, CA USA. EM dcraig@tgen.org; nschork@scripps.edu; jkelsoe@ucsd.edu RI ; Guo, Yiran/H-4120-2011; Liu, Chunyu/G-7561-2012; Smith, Erin/E-5933-2011; McInnis, Melvin/F-6963-2012; Greenwood, Tiffany/F-6356-2012; Schulze, Thomas/H-2157-2013; Zhang, Peng/N-2920-2014 OI McMahon, Francis/0000-0002-9469-305X; Edenberg, Howard/0000-0003-0344-9690; Guo, Yiran/0000-0002-6549-8589; Liu, Chunyu/0000-0002-5986-4415; McInnis, Melvin/0000-0002-0375-6247; Greenwood, Tiffany/0000-0002-6080-6503; Zhang, Peng/0000-0003-1182-1392; Nievergelt, Caroline/0000-0001-5766-8923; Nurnberger, John/0000-0002-7674-1767; Lawson, William/0000-0002-9324-7090 FU NIMH; NHGRI [MH078151, MH081804, MH059567]; Genetic Association Information Network (GAIN); Tzedakah Foundation; NIH [R01 MH59553]; Philip and Marcia Cohen; Scripps Translational Sciences Institute; NIH/NCRR [UL1 RR025774]; Scripps Genomic Medicine FX This work was supported by grants from the NIMH and NHGRI to JRK (MH078151, MH081804, MH059567 supplement) and by the Genetic Association Information Network (GAIN). This work was additionally funded in part by the NIMH Intramural Research Program (FJM and TGS). WHB was supported by a grant from the Tzedakah Foundation, a grant from NIH (R01 MH59553), and a grant from Philip and Marcia Cohen. ENS, CSB, SSM, and NJS are supported in part by the Scripps Translational Sciences Institute Clinical Translational Science Award [NIH/NCRR Grant Number UL1 RR025774] and Scripps Genomic Medicine. DWC and CP would like to acknowledge the Stardust foundation. Follow-up genotyping was performed in the laboratory of HJE at Indiana University School of Medicine. Data and biomaterials were collected in four projects that participated in the National Institute of Mental Health (NIMH) Bipolar Disorder Genetics Initiative. From 1991-1998, the Principal Investigators and Co-Investigators were: Indiana University, Indianapolis, IN, U01 MH46282, John Nurnberger, M. D., Ph. D., Marvin Miller, M. D., and Elizabeth Bowman, M. D.; Washington University, St. Louis, MO, U01 MH46280, Theodore Reich, M. D., Allison Goate, Ph. D., and John Rice, Ph. D.; Johns Hopkins University, Baltimore, MD U01 MH46274, J. Raymond DePaulo, Jr., M. D., Sylvia Simpson, M. D., MPH, and Colin Stine, Ph. D.; NIMH Intramural Research Program, Clinical Neurogenetics Branch, Bethesda, MD, Elliot Gershon, M. D., Diane Kazuba, B. A., and Elizabeth Maxwell, M. S. W. Data and biomaterials were collected as part of ten projects that participated in the National Institute of Mental Health (NIMH) Bipolar Disorder Genetics Initiative. From 1999-2007, the Principal Investigators and Co-Investigators were: Indiana University, Indianapolis, IN, R01 MH59545, John Nurnberger, M. D., Ph. D., Marvin J. Miller, M. D., Elizabeth S. Bowman, M. D., N. Leela Rau, M. D., P. Ryan Moe, M. D., Nalini Samavedy, M. D., Rif El-Mallakh, M. D. (at University of Louisville), Husseini Manji, M. D. (at Wayne State University), Debra A. Glitz, M. D. (at Wayne State University), Eric T. Meyer, M. S., Carrie Smiley, R. N., Tatiana Foroud, Ph. D., Leah Flury, M. S., Danielle M. Dick, Ph. D., Howard J. Edenberg, Ph. D.; Washington University, St. Louis, MO, R01 MH059534, John Rice, Ph. D, Theodore Reich, M. D., Allison Goate, Ph. D., Laura Bierut, M. D.; Johns Hopkins University, Baltimore, MD, R01 MH59533, Melvin McInnis M. D., J. Raymond DePaulo, Jr., M. D., Dean F. MacKinnon, M. D., Francis M. Mondimore, M. D., James B. Potash, M. D., Peter P. Zandi, Ph. D, Dimitrios Avramopoulos, and Jennifer Payne; University of Pennsylvania, PA, R01 MH59553, Wade Berrettini M. D., Ph. D.; University of California at Irvine, CA, R01 MH60068, William Byerley M. D., and Mark Vawter M. D.; University of Iowa, IA, R01 MH059548, William Coryell M. D., and Raymond Crowe M. D.; University of Chicago, IL, R01 MH59535, Elliot Gershon, M. D., Judith Badner Ph. D., Francis McMahon M. D., Chunyu Liu Ph. D., Alan Sanders M. D., Maria Caserta, Stephen Dinwiddie M. D., Tu Nguyen, Donna Harakal; University of California at San Diego, CA, R01 MH59567, John Kelsoe, M. D., Rebecca McKinney, B. A.; Rush University, IL, R01 MH059556, William Scheftner M. D., Howard M. Kravitz, D. O., M. P. H., Diana Marta, B. S., Annette Vaughn-Brown, MSN, RN, and Laurie Bederow, MA; NIMH Intramural Research Program, Bethesda, MD, 1Z01MH002810-01, Francis J. McMahon, M. D., Layla Kassem, PsyD, Sevilla Detera-Wadleigh, Ph. D, Lisa Austin, Ph. D, Dennis L. Murphy, M. D.; Data nd biomaterials from the NIMH GI (Genetics Initiative) MGS2 (Molecular Genetics of Schizophrenia) control sample were collected by NorthShore University HealthSystem, Evanston, IL, R01 MH59571, Pablo V. Gejman, M. D. (Collaboration Coordinator; PI) as part of a collaborative R01 application comprised of ten sites. From 2003-2006, the Principal Investigators and Co-Investigators were: NorthShore University HealthSystem, Evanston, IL, R01 MH59571, Pablo V. Gejman, M. D. (Collaboration Coordinator; PI), Alan R. Sanders, M. D.; Emory University School of Medicine, Atlanta, GA, R01 MH59587, Farooq Amin, M. D. (PI); University of California, San Francisco, CA, R01 MH60870, William F. Byerley, M. D. (PI); University of Iowa, Iowa, IA, R01 MH59566, Donald W. Black, M. D. (PI), Raymond R. Crowe, M. D.; Washington University, St. Louis, MO, R01 MH60879, C. Robert Cloninger, M. D. (PI); University of Colorado, Denver, CO, R01 MH59565, Robert Freedman, M. D. (PI), Ann Olincy, M. D.; Stanford University, Palo Alto, CA, R01 MH61675, Douglas F. Levinson, M. D. (PI); Louisiana State University, New Orleans, LA, R01 MH67257, Nancy G. Buccola, APRN, BC, MSN (PI); University of Queensland, Brisbane, Queensland, Australia, R01 MH59588, Bryan J. Mowry, M. D. (PI); Mt. Sinai School of Medicine, New York, NY, R01 MH59586, Jeremy M. Silverman, Ph. D. (PI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 36 Z9 37 U1 1 U2 3 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 JUN PY 2011 VL 7 IS 6 AR e1002134 DI 10.1371/journal.pgen.1002134 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 787OJ UT WOS:000292386300049 PM 21738484 ER PT J AU Korthuis, PT Berkenblit, GV Sullivan, LE Cofrancesco, J Cook, RL Bass, M Bashook, PG Edison, M Asch, SM Sosman, JM AF Korthuis, P. Todd Berkenblit, Gail V. Sullivan, Lynn E. Cofrancesco, Joseph, Jr. Cook, Robert L. Bass, Michael Bashook, Philip G. Edison, Marcia Asch, Steve M. Sosman, James M. TI GENERAL INTERNISTS' BELIEFS, BEHAVIORS, AND PERCEIVED BARRIERS TO ROUTINE HIV SCREENING IN PRIMARY CARE SO AIDS EDUCATION AND PREVENTION LA English DT Article ID COMMUNITY-HEALTH-CENTER; FOR-DISEASE-CONTROL; UNITED-STATES; EMERGENCY-DEPARTMENT; PREVENTIVE SERVICES; PREVALENCE; PHYSICIANS; SETTINGS; VETERANS; RECOMMENDATIONS AB The Centers for Disease Control and Prevention (CDC) recommends routine HIV screening in primary care but little is known about general internists' views of this practice. We conducted a national, cross-sectional, Internet-based survey of 446 general internists in 2009 regarding their HIV screening behaviors, beliefs, and perceived barriers to routine HIV screening in outpatient internal medicine practices. Internists' awareness of revised CDC guidelines was high (88%), but only 52% had increased HIV testing, 61% offered HIV screening regardless of risk, and a median 2% (range 0-67%) of their patients were tested in the past month. Internists practicing in perceived higher risk communities reported greater HIV screening. Consent requirements were a barrier to screening, particularly for VA providers and those practicing in states with HIV consent statutes inconsistent with CDC guidelines. Interventions that promote HIV screening regardless of risk and streamlined consent requirements will likely increase adoption of routine HIV screening in general medicine practices. C1 [Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Berkenblit, Gail V.; Cofrancesco, Joseph, Jr.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Sullivan, Lynn E.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Cook, Robert L.] Univ Florida, Dept Med, Gainesville, FL USA. [Cook, Robert L.] Univ Florida, Dept Epidemiol, Gainesville, FL USA. [Bass, Michael; Bashook, Philip G.; Edison, Marcia] Univ Illinois, Coll Med, Dept Med Educ, Chicago, IL USA. [Asch, Steve M.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Sosman, James M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53706 USA. RP Korthuis, PT (reprint author), Oregon Hlth & Sci Univ, Dept Med, 3181 SW Sam Jackson Pk Rd,Mail Code L-475, Portland, OR 97239 USA. EM korthuis@ohsu.edu FU NCHHSTP CDC HHS [1 U22 PS00551-02, U22 PS000551]; NIDA NIH HHS [K23 DA019809] NR 30 TC 27 Z9 27 U1 1 U2 4 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0899-9546 J9 AIDS EDUC PREV JI Aids Educ. Prev. PD JUN PY 2011 VL 23 IS 3 SU S BP 70 EP 83 PG 14 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 779FQ UT WOS:000291763900007 PM 21689038 ER PT J AU Thase, ME AF Thase, Michael E. TI Antidepressant Combinations: Widely Used, But Far From Empirically Validated SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Article DE antidepressants; combined therapy; polypharmacy; treatment-resistant depression ID TREATMENT-RESISTANT DEPRESSION; DOUBLE-BLIND; CONTROLLED MULTICENTER; REFRACTORY DEPRESSION; MAJOR DEPRESSION; BUPROPION-SR; AUGMENTATION; FLUOXETINE; CLOMIPRAMINE; DESIPRAMINE AB This paper reviews the evidence on combining antidepressants (ADs) for treatment of major depressive disorder. Although widely used and usually safe, the efficacy of even the most widely prescribed combinations of ADs has not been established by properly controlled, adequately powered, clinical trials. This stands in contrast to several adjunctive strategies for AD nonresponders, including adjunctive lithium, thyroid hormone, or newer-generation antipsychotics. The wide use of AD combinations no doubt reflects the limited efficacy of commonly used ADs and the unmet need for effective strategies for patients with treatment-resistant depression. Although of unproven efficacy, potential merits of combining selected ADs include: 1) avoiding discontinuation-emergent symptoms and cross-titration schedules, 2) at worst, the second AD should be as effective in combination as it would be as a monotherapy following a switch, and 3) the possibility of complementary neuropharmacologic effects that may enhance efficacy or improve tolerability. The dearth of controlled studies of such a commonly used strategy for such a highly prevalent condition is symptomatic of shortcomings in the way clinically relevant research is funded, points to the need for industry academic federal collaborations, and underscores the need for large, practice-based, research groups that can efficiently complete publicly funded studies of high public health impact. C1 [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP Thase, ME (reprint author), Univ Penn, Sch Med, Philadelphia, PA 19104 USA. EM thase@mail.med.upenn.edu FU Eli Lilly Company; GlaxoSmithKline; National Institute of Mental Health; Agency for Healthcare Research and Quality, Sepracor, Inc FX Preparation of this manuscript was not supported by any external funding source. Dr Thase discloses relationships with the manufacturers of all ADs and most antipsychotics introduced from 1980 onward, including: scientific consultation to Astra-Zeneca, Bristol-Myers Squibb Company, Dey Pharma, LP, Eli Lilly & Company, Forest Pharmaceuticals, Inc, Gerson Lehman Group, GlaxoSmithKline, Guidepoint Global, H Lundbeck A/S, MedAvante, Inc, Merck and Co Inc, Neuronetics, Inc, Novartis, Otsuka, Ortho-McNeil Pharmaceuticals, PamLab, LLC, Pfizer (formerly Wyeth-Ayerst Laboratories), Schering-Plough, Shire US Inc, Supernus Pharmaceuticals, Takeda (Lundbeck), and Transcept Pharmaceuticals. Dr Thase has been a member of the speakers' bureaus for AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly & Company, Merck and Co Inc, and Pfizer (formerly Wyeth-Ayerst Laboratories). He receives grant funding from Eli Lilly & Company, GlaxoSmithKline, National Institute of Mental Health, and Agency for Healthcare Research and Quality, Sepracor, Inc. Dr Thase has equity holdings in MedAvante, Inc, and receives royalty income from American Psychiatric Publishing, Inc, Guilford Publications, Herald House, Oxford University Press, and W W Norton & Company. Dr Thase's wife is employed as the Group Scientific Director for Embryon (formerly Advogent), which does business with BMS and Pfizer/Wyeth. The editorial assistance of Ms Christine Johnson is also gratefully acknowledged. NR 15 TC 18 Z9 18 U1 0 U2 5 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 141 LAURIER AVENUE WEST, STE 701, OTTAWA, ONTARIO K1P 5J3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD JUN PY 2011 VL 56 IS 6 BP 317 EP 323 PG 7 WC Psychiatry SC Psychiatry GA 779GI UT WOS:000291765700002 PM 21756445 ER PT J AU Spiegel, BMR AF Spiegel, Brennan M. R. TI Questioning the Bacterial Overgrowth Hypothesis of Irritable Bowel Syndrome: An Epidemiologic and Evolutionary Perspective SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Review DE Irritable Bowel Syndrome; Small Intestinal Bacterial Overgrowth; Epidemiology ID PLACEBO-CONTROLLED TRIAL; FUNCTIONAL GASTROINTESTINAL DISORDERS; CHLORIDE CHANNEL ACTIVATOR; GULF-WAR VETERANS; DOUBLE-BLIND; BREATH TEST; CHRONIC CONSTIPATION; RECEPTOR ANTAGONIST; HEALTHY CONTROLS; CLINICAL-TRIAL AB Although studies indicate that small intestinal bacterial overgrowth (SIBO) is prevalent in irritable bowel syndrome (IBS), it remains unclear whether SIBO causes IBS. This review presents an epidemiologic and evolutionary inquiry that questions the bacterial overgrowth hypothesis of IBS, as follows. (1) Although the hypothesis may be biologically plausible, there is also a strong rationale for competing hypotheses; it is unlikely that SIBO is the predominant cause of IBS in all comers, because competing explanations are sensible and defensible. Moreover, data indicate that the test used to promulgate the SIBO hypothesis - the lactulose hydrogen breath test - may not have measured SIBO in the first place. (2) We do not have evidence of SIBO being absent before IBS symptoms, and present after IBS emerges. (3) There is not a dose-response relationship between small intestinal microbiota and IBS symptoms. (4) The relationship between SIBO and IBS is highly inconsistent among studies. (5) Many effective IBS therapies do not address SIBO at all, yet have a more favorable "number needed to treat" than antibiotics. (6) IBS does not behave like a traditional infectious disease, suggesting that microbes may not principally cause the syndrome. (7) Other factors may confound the relationship between SIBO and IBS, including proton pump inhibitors. (8) Whereas the brain-gut hypothesis is evolutionary sensible, the bacterial hypothesis is harder to defend from an evolutionary perspective. The article concludes that bacteria may contribute to some IBS symptoms, but that bacteria cannot be the only explanation, and a causal link between SIBO and IBS is not secure. C1 [Spiegel, Brennan M. R.] VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90095 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Los Angeles, CA 90095 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ, Los Angeles, CA 90095 USA. RP Spiegel, BMR (reprint author), 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU AstraZeneca; Prometheus; Rose Pharma A/G; Shire; Takeda FX The author discloses the following: The author has served as an advisor for AstraZeneca, Movetis, Procter and Gamble, Prometheus, Ironwood, Rose Pharma A/G, Salix, Shire, and Takeda, and has received grant support from AstraZeneca, Prometheus, Rose Pharma A/G, Shire, and Takeda. This review is unfunded. NR 96 TC 32 Z9 36 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUN PY 2011 VL 9 IS 6 BP 461 EP 469 DI 10.1016/j.cgh.2011.02.030 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 778HA UT WOS:000291693300010 PM 21397724 ER PT J AU Aneshensel, CS Ko, MJ Chodosh, J Wight, RG AF Aneshensel, Carol S. Ko, Michelle J. Chodosh, Joshua Wight, Richard G. TI The Urban Neighborhood and Cognitive Functioning in Late Middle Age SO JOURNAL OF HEALTH AND SOCIAL BEHAVIOR LA English DT Article DE cognition; ecological model; multilevel model; neighborhood ID OLDER MEXICAN-AMERICANS; MENTAL-HEALTH; DEPRESSIVE SYMPTOMS; RESIDENTIAL SEGREGATION; EDUCATIONAL-ATTAINMENT; LATER LIFE; FOLLOW-UP; CONTEXT; DEMENTIA; DISPARITIES AB This study examines the association of cognitive functioning with urban neighborhood socioeconomic disadvantage and racial/ethnic segregation for a U.S. national sample of persons in late middle age, a time in the life course when cognitive deficits begin to emerge. The key hypothesis is that effects of neighborhood on cognitive functioning are not uniform but are most pronounced among subgroups of the population defined by socioeconomic status and race/ethnicity. Data are from the third wave of the Health and Retirement Survey for the birth cohort of 1931 to 1941, which was 55 to 65 years of age in 1996 (analytic N = 4,525), and the 1990 U.S. Census. Neighborhood socioeconomic disadvantage has an especially large negative impact on cognitive functioning among persons who are themselves poor, an instance of compound disadvantage. These findings have policy implications supporting "upstream" interventions to enhance cognitive functioning, especially among those most adversely affected by neighborhood socioeconomic disadvantage. C1 [Aneshensel, Carol S.; Wight, Richard G.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA 90095 USA. [Ko, Michelle J.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90095 USA. [Chodosh, Joshua] Univ Calif Los Angeles, Div Geriatr, Los Angeles, CA 90095 USA. [Chodosh, Joshua] Vet Adm Greater Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. RP Aneshensel, CS (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Box 951772,650 Young Dr S, Los Angeles, CA 90095 USA. EM anshnsl@ucla.edu OI Chodosh, Joshua/0000-0001-7784-4306 FU NIA NIH HHS [R01 AG022537, R01 AG022537-05] NR 55 TC 14 Z9 14 U1 3 U2 18 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-1465 J9 J HEALTH SOC BEHAV JI J. Health Soc. Behav. PD JUN PY 2011 VL 52 IS 2 BP 163 EP 179 DI 10.1177/0022146510393974 PG 17 WC Public, Environmental & Occupational Health; Psychology, Social SC Public, Environmental & Occupational Health; Psychology GA 777JN UT WOS:000291611900002 PM 21673145 ER PT J AU Riopelle, D Wagner, GJ Steckart, J Lorenz, KA Rosenfeld, KE AF Riopelle, Deborah Wagner, Glenn J. Steckart, Jillisa Lorenz, Karl A. Rosenfeld, Kenneth E. TI Evaluating a Palliative Care Intervention for Veterans: Challenges and Lessons Learned in a Longitudinal Study of Patients with Serious Illness SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Palliative care; research challenges; retention; data collection ID AFTER-DEATH INTERVIEWS; QUALITY-OF-LIFE; RECRUITING PATIENTS; RANDOMIZED-TRIAL; CANCER PATIENTS; SUPPORT; ISSUES; ILL; SATISFACTION; RETENTION AB Context. Longitudinal studies examining care for seriously ill patients are needed to understand patients' experience of illness, evaluate interventions, and improve quality of care. Unfortunately, such studies face substantial methodological challenges. Objectives. This article describes such challenges and the strategies used to overcome them in a successfully implemented palliative care intervention trial for veterans. Methods. Veterans admitted with a physician-estimated moderate-to-high one-year mortality risk were enrolled and followed up to three years, until death or study completion. Study protocols, procedures, and process data were intermittently analyzed to identify and develop strategies to address issues affecting study enrollment and interview completion rates. Results. Of 561 patients who were eligible, 400 (71%) enrolled in the study; 357 (87%) alive at the end of Month 1 completed interviews; and 254 (88%) alive at Month 6 completed interviews. Of the 208 patients who died during the study and had identified a caregiver, we were able to conduct an after-death interview with 154 (74%) caregivers. A variety of strategies, such as systematic tracking and checkin calls, minimizing respondent burden, and maintaining interviewer-respondent dyads over time, were used to maximize enrollment rates, data collection, and retention. Conclusion. These data demonstrate that the use of diverse strategies and flexibility with regard to study protocols can result in successful recruitment, data collection, and retention of participants with serious illness. They thus show that longitudinal research can be successfully implemented with this population to evaluate interventions and examine patient experiences. J Pain Symptom Manage 2011; 41: 1003-1014. Published by Elsevier Inc. on behalf of U.S. Cancer Pain Relief Committee. C1 [Wagner, Glenn J.] RAND Corp, Santa Monica, CA 90407 USA. [Riopelle, Deborah; Steckart, Jillisa; Lorenz, Karl A.; Rosenfeld, Kenneth E.] Vet Adm Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. RP Wagner, GJ (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90407 USA. EM gwagner@rand.org FU VA HSRD [IIR 2-294] FX Support was provided by the VA Center for the Study of Healthcare Provider Behavior and funding provided by VA HSR&D grant IIR 2-294 (P.I., Dr. Rosenfeld). The authors declare no conflicts of interest. NR 27 TC 3 Z9 3 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUN PY 2011 VL 41 IS 6 BP 1003 EP 1014 DI 10.1016/j.jpainsymman.2010.09.023 PG 12 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 779VG UT WOS:000291809700007 PM 21402457 ER PT J AU Ding, D Cooper, RA Pasquina, PF Fici-Pasquina, L AF Ding, Dan Cooper, Rory A. Pasquina, Paul F. Fici-Pasquina, Lavinia TI Sensor technology for smart homes SO MATURITAS LA English DT Review DE Smart homes; Sensor technology; Independent living; Aging; Disability AB A smart home is a residence equipped with technology that observes the residents and provides proactive services. Most recently, it has been introduced as a potential solution to support independent living of people with disabilities and older adults, as well as to relieve the workload from family caregivers and health providers. One of the key supporting features of a smart home is its ability to monitor the activities of daily living and safety of residents, and in detecting changes in their daily routines. With the availability of inexpensive low-power sensors, radios, and embedded processors, current smart homes are typically equipped with a large amount of networked sensors which collaboratively process and make deductions from the acquired data on the state of the home as well as the activities and behaviors of its residents. This article reviews sensor technology used in smart homes with a focus on direct environment sensing and infrastructure mediated sensing. The article also points out the strengths and limitations of different sensor technologies, as well as discusses challenges and opportunities from clinical, technical, and ethical perspectives. It is recommended that sensor technologies for smart homes address actual needs of all stake holders including end users, their family members and caregivers, and their doctors and therapists. More evidence on the appropriateness, usefulness, and cost benefits analysis of sensor technologies for smart homes is necessary before these sensors should be widely deployed into real-world residential settings and successfully integrated into everyday life and health care services. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Ding, Dan; Cooper, Rory A.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15260 USA. [Ding, Dan; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. [Pasquina, Paul F.] Walter Reed Army Med Ctr, Dept Orthoped & Rehabil, Washington, DC 20307 USA. [Fici-Pasquina, Lavinia] Catholic Univ Amer, Dept Architecture, Washington, DC 20064 USA. RP Ding, D (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Labs, 7180 Highland Dr,151R1-H, Pittsburgh, PA 15260 USA. EM dad5@pitt.edu FU National Science Foundation [EEC-0540865]; VA Center of Excellence for Wheelchairs and Associated Rehabilitation Engineering [B3142C] FX The work is supported in part by the Quality of Life Technology Engineering Research Center (EEC-0540865) funded by the National Science Foundation. The work is also supported by VA Center of Excellence for Wheelchairs and Associated Rehabilitation Engineering B3142C. The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government. NR 44 TC 57 Z9 58 U1 10 U2 64 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-5122 J9 MATURITAS JI Maturitas PD JUN PY 2011 VL 69 IS 2 BP 131 EP 136 DI 10.1016/j.maturitas.2011.03.016 PG 6 WC Geriatrics & Gerontology; Obstetrics & Gynecology SC Geriatrics & Gerontology; Obstetrics & Gynecology GA 780EP UT WOS:000291837600008 PM 21531517 ER PT J AU Williams, EC Johnson, ML Lapham, GT Caldeiro, RM Chew, L Fletcher, GS McCormick, KA Weppner, WG Bradley, KA AF Williams, Emily C. Johnson, M. Laura Lapham, Gwen T. Caldeiro, Ryan M. Chew, Lisa Fletcher, Grant S. McCormick, Kinsey A. Weppner, William G. Bradley, Katharine A. TI Strategies to Implement Alcohol Screening and Brief Intervention in Primary Care Settings: A Structured Literature Review SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Review DE alcohol screening; brief intervention; systematic review; implementation; unhealthy alcohol use ID PRIMARY-HEALTH-CARE; BEHAVIORAL-COUNSELING INTERVENTIONS; ELECTRONIC CLINICAL REMINDER; RANDOMIZED CONTROLLED-TRIAL; QUALITY IMPROVEMENT; PREVENTIVE-SERVICES; COST-EFFECTIVENESS; FRAMEWORK; NURSES; DISSEMINATION AB Although alcohol screening and brief intervention (SBI) reduces drinking in primary care patients with unhealthy alcohol use, incorporating SBI into clinical settings has been challenging. We systematically reviewed the literature on implementation studies of alcohol SBI using a broad conceptual model of implementation, the Consolidated Framework for Implementation Research (CFIR), to identify domains addressed by programs that achieved high rates of screening and/or brief intervention (BI). Seventeen articles from 8 implementation programs were included; studies were conducted in 9 countries and represented 533,903 patients (127,304 patients screened), 2,001 providers, and 1,805 clinics. Rates of SBI varied across articles (2-93% for screening and 0.9-73.1% for BI). Implementation programs described use of 7-25 of the 39 CFIR elements. Most programs used strategies that spanned all 5 domains of the CFIR with varying emphases on particular domains and sub-domains. Comparison of SBI rates was limited by most studies' being conducted by 2 implementation programs and by different outcome measures, scopes, and durations. However, one implementation program reported a high rate of screening relative to other programs (93%) and could be distinguished by its use of strategies that related to the Inner Setting, Outer Setting, and Process of Implementation domains of the CFIR. Future studies could assess whether focusing on Inner Setting, Outer Setting, and Process of Implementation elements of the CFIR during implementation is associated with successful implementation of alcohol screening, as well as which elements may be associated with successful, sustained implementation of BI. C1 [Williams, Emily C.; Johnson, M. Laura; Lapham, Gwen T.; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Williams, Emily C.; Johnson, M. Laura; Lapham, Gwen T.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Caldeiro, Ryan M.] Grp Hlth Cooperat Puget Sound, Chem Dependency Serv, Seattle, WA 98121 USA. [Caldeiro, Ryan M.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Chew, Lisa; Fletcher, Grant S.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Chew, Lisa; Fletcher, Grant S.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98104 USA. [McCormick, Kinsey A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Weppner, William G.] Boise VA Med Ctr, Boise, ID USA. RP Williams, EC (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM emily.williams3@va.gov NR 41 TC 50 Z9 52 U1 3 U2 17 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X EI 1939-1501 J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD JUN PY 2011 VL 25 IS 2 BP 206 EP 214 DI 10.1037/a0022102 PG 9 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 778SZ UT WOS:000291727300003 PM 21517141 ER PT J AU Gordon, AJ Kavanagh, G Krumm, M Ramgopal, R Paidisetty, S Aghevli, M Goodman, F Trafton, J Liberto, J AF Gordon, Adam J. Kavanagh, Greg Krumm, Margaret Ramgopal, Rajeev Paidisetty, Sanjay Aghevli, Minu Goodman, Francine Trafton, Jodie Liberto, Joseph TI Facilitators and Barriers in Implementing Buprenorphine in the Veterans Health Administration SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE opioid-related disorders; buprenorphine; United States Department of Veterans Affairs ID OFFICE-BASED TREATMENT; OPIOID DEPENDENCE; PRIMARY-CARE; OPIATE ADDICTION; METHADONE; NALOXONE; THERAPY; COSTS; QUERI AB Opioid dependence is a chronic, relapsing disorder that deleteriously influences the health of those afflicted. Sublingual buprenorphine opioid agonist treatment (OAT) has been shown to be safe, effective, and cost-effective for the treatment of opioid dependence in nonspecialized, office-based settings, including the Veterans Health Administration (VHA). We sought to examine and describe provider-, facility-, and system-level barriers and facilitators to implementing buprenorphine therapy within the VHA. From June 2006 to October 2007, we conducted semistructured telephone interviews of key personnel at a national sample of VHA facilities with high prevalence of opioid dependence and without methadone OAT programs. Sites were categorized based on the number of veterans receiving buprenorphine prescriptions: More Buprenorphine (MB, >40 prescriptions, 5 sites), Some Buprenorphine (SB, 5-40 prescriptions, 3 sites), and No Buprenorphine (NB, 0-5 prescriptions, 9 sites). Interviews were taped, transcribed, and coded; consensus of coding themes was reached; and data were evaluated using grounded theory. Sixty-two staff members were interviewed. For NB sites, perceived patient barriers included lack of need and attitudes/stigma associated with opioid dependence. Provider barriers included lack of interest, stigma toward the population, and lack of education about buprenorphine-OAT. Prominent facilitators at MB sites included having established need, provider interest, and resources/time available for buprenorphine-OAT. The presence of a champion/role-model for buprenorphine care greatly facilitated its implementation. We conclude that factors that enable or impede buprenorphine-OAT vary by facility. Strategies and policies to encourage implementation of buprenorphine should be adaptable and target needs of each facility. C1 [Gordon, Adam J.; Krumm, Margaret; Ramgopal, Rajeev] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA. [Gordon, Adam J.; Krumm, Margaret] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Gordon, Adam J.] Univ Pittsburgh, Dept Med, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. [Kavanagh, Greg; Aghevli, Minu] VA Maryland Hlth Care Syst, Baltimore, MD USA. [Paidisetty, Sanjay] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Goodman, Francine] Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA. [Trafton, Jodie] VA Palo Alto Hlth Care Syst, Program Evaluat & Resource Ctr, Palo Alto, CA USA. [Trafton, Jodie] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. [Liberto, Joseph] Univ Maryland, VA Maryland Hlth Care Syst, Sch Med, Baltimore, MD 21201 USA. [Liberto, Joseph] Univ Maryland, Dept Psychiat, Sch Med, Baltimore, MD 21201 USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Mailcode 151C-H CHERP, Pittsburgh, PA 15206 USA. EM adam.gordon@va.gov NR 34 TC 22 Z9 22 U1 3 U2 7 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X EI 1939-1501 J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD JUN PY 2011 VL 25 IS 2 BP 215 EP 224 DI 10.1037/a0022776 PG 10 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 778SZ UT WOS:000291727300004 PM 21480679 ER PT J AU Lash, SJ Timko, C Curran, GM Mckay, JR Burden, JL AF Lash, Steven J. Timko, Christine Curran, Geoffery M. Mckay, James R. Burden, Jennifer L. TI Implementation of Evidence-Based Substance Use Disorder Continuing Care Interventions SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE substance dependence; alcohol dependence; continuing care; mutual help groups; implementation ID SELF-HELP GROUPS; ALCOHOLICS-ANONYMOUS AFFILIATION; RANDOMIZED CLINICAL-TRIAL; CHANGING NETWORK SUPPORT; HEALTH-SERVICES RESEARCH; AFTERCARE GROUP-THERAPY; ABUSE TREATMENT; OUTPATIENT TREATMENT; ADDICTION TREATMENT; FOLLOW-UP AB Continuing care following initial substance use disorder treatment often is associated with improved treatment outcomes and evidence-based interventions (EBIs) have been developed in this area. However, rates of patient participation in continuing care treatment and mutual help groups (MHGs) are low and a large gap exists between the existing EBIs and actual clinical care. This paper uses the Consolidated Framework for Implementation Research (CFIR; Damschroder et al., 2009) to review the literature on continuing care treatment and monitoring, and mutual help-group promotion. Although existing research provides implications for implementing EBIs in continuing care, few direct implementation trials have been conducted. This literature indicates that EBIs in continuing care have been successfully modified for different settings, that they can be delivered using different modalities (e.g., individual, group, and telephone-based care), and that low cost options are available. Additionally, much is known about the differential effectiveness of continuing care with different populations that may guide treatment programs and providers in selecting the most effective interventions for their clients. One significant barrier to successful implementation of EBIs for continuing care is the lack of information about incentives for providing continuing care across what in the CFIR terminology is a program's outer setting (i.e., external economic, political, and social setting), and its inner setting (i.e., internal political, structural, and cultural contexts). Implications for implementation of EBIs in substance use disorder continuing care are discussed. C1 [Lash, Steven J.] Vet Affairs Med Ctr, Dept Psychiat & Neurobehav Sci, Salem, VA 24153 USA. [Lash, Steven J.] Univ Virginia, Charlottesville, VA 22903 USA. [Timko, Christine] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Mckay, James R.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Mckay, James R.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Lash, SJ (reprint author), Vet Affairs Med Ctr, Dept Psychiat & Neurobehav Sci, SARRTP 116A4, Salem, VA 24153 USA. EM Steven.Lash@va.gov NR 107 TC 19 Z9 19 U1 5 U2 19 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X EI 1939-1501 J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD JUN PY 2011 VL 25 IS 2 BP 238 EP 251 DI 10.1037/a0022608 PG 14 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 778SZ UT WOS:000291727300006 PM 21443297 ER PT J AU Weinstock, J Burton, S Rash, CJ Moran, S Biller, W Krudelbach, N Phoenix, N Morasco, BJ AF Weinstock, Jeremiah Burton, Steve Rash, Carla J. Moran, Sheila Biller, Warren Krudelbach, Norman Phoenix, Natalie Morasco, Benjamin J. TI Predictors of Engaging in Problem Gambling Treatment: Data From the West Virginia Problem Gamblers Help Network SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE gambling; treatment; initiation ID MENTAL-HEALTH-SERVICES; MISSING DATA; PATHOLOGICAL GAMBLERS; MULTIPLE IMPUTATION; TREATMENT-SEEKING; TREATMENT ENTRY; PART 2; CALLERS; RECOVERY; COERCION AB Gambling help-lines are an essential access point, or frontline resource, for treatment seeking. This study investigated treatment engagement after calling a gambling help-line. From 2000-2007 over 2,900 unique callers were offered an in-person assessment appointment. Logistic regression analyses assessed predictors of (a) accepting the referral to the in-person assessment appointment and (b) attending the in-person assessment appointment. Over 76% of callers accepted the referral and 55% of all callers attended the in-person assessment appointment. This treatment engagement rate is higher than typically found for other help-lines. Demographic factors and clinical factors such as gender, severity of gambling problems, amount of gambling debt, and coercion by legal and social networks predicted engagement in treatment. Programmatic factors such as offering an appointment within 72 hr also aided treatment engagement. Results suggest gambling help-lines can be a convenient and confidential way for many individuals with gambling problems to access gambling-specific treatment. Alternative services such as telephone counseling may be beneficial for those who do not engage in treatment. C1 [Weinstock, Jeremiah; Rash, Carla J.; Phoenix, Natalie] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Weinstock, Jeremiah] St Louis Univ, Dept Psychol, St Louis, MO 63103 USA. [Burton, Steve; Moran, Sheila; Biller, Warren; Krudelbach, Norman] Problem Gamblers Help Network W Virginia, Charleston, WV USA. [Morasco, Benjamin J.] Portland VA Med Ctr, Portland, OR USA. [Morasco, Benjamin J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Weinstock, J (reprint author), St Louis Univ, Dept Psychol, 3511 Laclede Ave, St Louis, MO 63103 USA. EM jweinsto@slu.edu FU NIAAA NIH HHS [T32-AA07290, T32 AA007290, R21-AA017717, R21 AA017717-02, R21 AA017717]; NIDA NIH HHS [K23-DA023467, K23 DA023467-02, K23 DA023467] NR 44 TC 17 Z9 17 U1 2 U2 5 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD JUN PY 2011 VL 25 IS 2 BP 372 EP 379 DI 10.1037/a0023240 PG 8 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 778SZ UT WOS:000291727300022 PM 21480678 ER PT J AU Watson, RR Binmoeller, KF Hamerski, CM Shergill, AK Shaw, RE Jaffee, IM Stewart, L Shah, JN AF Watson, Rabindra R. Binmoeller, Kenneth F. Hamerski, Chris M. Shergill, Amandeep K. Shaw, Richard E. Jaffee, Ian M. Stewart, Lygia Shah, Janak N. TI Yield and Performance Characteristics of Endoscopic Ultrasound-Guided Fine Needle Aspiration for Diagnosing Upper GI Tract Stromal Tumors SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Gastrointestinal stromal tumors; Endoscopy; Endoscopic ultrasound; Fine needle aspiration; Gastrointestinal neoplasms ID GASTROINTESTINAL-TRACT; CELL TUMORS; FEATURES; BENIGN AB Background and Aims EUS-FNA is a means of sampling suspected GI stromal tumors (GIST). However, there are limited published data on factors influencing the sampling yield, and on the performance characteristics of this technique in comparison with resection pathology. We analyzed the yield of EUS-FNA for submucosal lesions of the upper GI tract, and determined the performance characteristics of EUS-FNA for diagnosing GISTs. Methods We retrospectively reviewed procedural and pathology data from consecutive patients undergoing EUS-FNA of submucosal lesions from two medical centers over a 4-year period. We analyzed the yield of EUS-FNA, and calculated performance characteristics of EUS-FNA for GIST based on resection pathology. Results A total of 65 patients underwent EUS-FNA of 66 submucosal lesions during the study period. EUS-FNA was either diagnostic (68%) or suspicious (12%) in a total of 80%. EUS-FNA yielded the following diagnoses: GIST based on cytology and immunohistochemistry (56%), suspected GIST (12%), leiomyoma (9%), other neoplasm (3%), and non-diagnostic (20%). Larger lesion size, gastric location, and presence of on-site cytopathology were associated with higher yield in univariate analysis. Larger needle size and number of FNA passes were not associated with improved yield. Based on resection pathology from 28 specimens, the EUS-FNA performance characteristics for diagnosing GISTs included a sensitivity of 82%, a specificity of 100%, and an overall accuracy of 86%. Conclusions EUS-FNA provides a high yield for sampling submucosal lesions and is highly accurate for diagnosing GISTs. EUS-FNA has an important role in the evaluation of suspected GISTs. C1 [Binmoeller, Kenneth F.; Shaw, Richard E.; Jaffee, Ian M.; Shah, Janak N.] UCSF, San Francisco VA Med Ctr, Calif Pacific Med Ctr, Intervent Endoscopy Serv,IES Lab, San Francisco, CA 95115 USA. RP Shah, JN (reprint author), UCSF, San Francisco VA Med Ctr, Calif Pacific Med Ctr, Intervent Endoscopy Serv,IES Lab, 2351 Clay St,6th Floor, San Francisco, CA 95115 USA. EM shahj@sutterhealth.org NR 16 TC 33 Z9 35 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 2011 VL 56 IS 6 BP 1757 EP 1762 DI 10.1007/s10620-011-1646-6 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 766HF UT WOS:000290770900024 PM 21360279 ER PT J AU Bayer-Carter, JL Green, PS Montine, TJ VanFossen, B Baker, LD Watson, S Bonner, LM Callaghan, M Leverenz, JB Walter, BK Tsai, E Plymate, SR Postupna, N Wilkinson, CW Zhang, J Lampe, J Kahn, SE Craft, S AF Bayer-Carter, Jennifer L. Green, Pattie S. Montine, Thomas J. VanFossen, Brian Baker, Laura D. Watson, Stennis Bonner, Laura M. Callaghan, Maureen Leverenz, James B. Walter, Brooke K. Tsai, Elaine Plymate, Stephen R. Postupna, Nadia Wilkinson, Charles W. Zhang, Jing Lampe, Johanna Kahn, Steven E. Craft, Suzanne TI Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment SO ARCHIVES OF NEUROLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; ALZHEIMERS-DISEASE; A-BETA; INSULIN-RESISTANCE; MOUSE MODEL; MEDITERRANEAN DIET; BRAIN; PLASMA; DEMENTIA; RISK AB Objective: To compare the effects of a 4-week high-saturated fat/high-glycemic index (HIGH) diet with a low-saturated fat/low-glycemic index (LOW) diet on insulin and lipid metabolism, cerebrospinal fluid (CSF) markers of Alzheimer disease, and cognition for healthy adults and adults with amnestic mild cognitive impairment (aMCI). Design: Randomized controlled trial. Setting: Veterans Affairs Medical Center clinical research unit. Participants: Forty-nine older adults (20 healthy adults with a mean [SD] age of 69.3 [7.4] years and 29 adults with aMCI with a mean [SD] age of 67.6 [6.8] years). Intervention: Participants received the HIGH diet (fat, 45% [saturated fat, >25%]; carbohydrates, 35%-40% [glycemic index, >70]; and protein, 15%-20%) or the LOW diet (fat, 25%; [saturated fat, <7%]; carbohydrates, 55%-60% [glycemic index, <55]; and protein, 15%-20%) for 4 weeks. Cognitive tests, an oral glucose tolerance test, and lumbar puncture were conducted at baseline and during the fourth week of the diet. Main Outcome Measures: The CSF concentrations of beta-amyloid (A beta 42 and A beta 40), tau protein, insulin, F2-isoprostanes, and apolipoprotein E, plasma lipids and insulin, and measures of cognition. Results: For the aMCI group, the LOW diet increased CSF A beta 42 concentrations, contrary to the pathologic pattern of lowered CSF A beta 42 typically observed in Alzheimer disease. The LOW diet had the opposite effect for healthy adults, ie, decreasing CSF A beta 42, whereas the HIGH diet increased CSF A beta 42. The CSF apolipoprotein E concentration was increased by the LOW diet and decreased by the HIGH diet for both groups. For the aMCI group, the CSF insulin concentration increased with the LOW diet, but the HIGH diet lowered the CSF insulin concentration for healthy adults. The HIGH diet increased and the LOW diet decreased plasma lipids, insulin, and CSF F2-isoprostane concentrations. Delayed visual memory improved for both groups after completion of 4 weeks of the LOW diet. Conclusion: Our results suggest that diet may be a powerful environmental factor that modulates Alzheimer disease risk through its effects on central nervous system concentrations of A beta 42, lipoproteins, oxidative stress, and insulin. C1 [Walter, Brooke K.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Dept Neurol, Seattle, WA 98108 USA. [Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. [Bayer-Carter, Jennifer L.; VanFossen, Brian; Baker, Laura D.; Watson, Stennis; Bonner, Laura M.; Wilkinson, Charles W.; Craft, Suzanne] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Green, Pattie S.; Tsai, Elaine; Plymate, Stephen R.; Kahn, Steven E.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Montine, Thomas J.; Postupna, Nadia; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Leverenz, James B.; Walter, Brooke K.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. [Lampe, Johanna] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Craft, S (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S 182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM scraft@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU National Institute on Aging [R37 AG-10880, P50 AG-05136, 5T32 AG-000258]; Nancy and Buster Alvord Endowment; Veterans Affairs Puget Sound Health Care System, Seattle, Washington FX This research was supported by grant R37 AG-10880 from the National Institute on Aging to Dr Craft, grant P50 AG-05136 to Dr Montine, and grant 5T32 AG-000258 to Dr Postupna and supported by funding from the Nancy and Buster Alvord Endowment to Dr Montine. This article results from work supported by resources from the Veterans Affairs Puget Sound Health Care System, Seattle, Washington. NR 59 TC 53 Z9 57 U1 0 U2 22 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 JUN PY 2011 VL 68 IS 6 BP 743 EP 752 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 776ON UT WOS:000291546100008 PM 21670398 ER PT J AU Martin, JL Hakim, AD AF Martin, Jennifer L. Hakim, Alex D. TI Wrist Actigraphy SO CHEST LA English DT Article ID OBSTRUCTIVE SLEEP-APNEA; NURSING-HOME RESIDENTS; CHRONIC PRIMARY INSOMNIA; PRACTICE PARAMETERS; MOTOR-ACTIVITY; BREATHING DISORDERS; CIRCADIAN-RHYTHMS; CONTROLLED-TRIAL; PHASE SYNDROME; NIGHT SHIFTS AB To record sleep, actigraph devices are worn on the wrist and record movements that can be used to estimate sleep parameters with specialized algorithms in computer software programs. With the recent establishment of a Current Procedural Terminology code for wrist actigraphy, this technology is being used increasingly in clinical settings as actigraphy has the advantage of providing objective information on sleep habits in the patient's natural sleep environment. Actigraphy has been well validated for the estimation of nighttime sleep parameters across age groups, but the validity of the estimation of sleep-onset latency and daytime sleeping is limited. Clinical guidelines and research suggest that wrist actigraphy is particularly useful in the documentation of sleep patterns prior to a multiple sleep latency test, in the evaluation of circadian rhythm sleep disorders, to evaluate treatment outcomes, and as an adjunct to home monitoring of sleep-disordered breathing. Actigraphy has also been well studied in the evaluation of sleep in the context of depression and dementia. Although actigraphy should not be viewed as a substitute for clinical interviews, sleep diaries, or overnight polysomnography when indicated, it can provide useful information about sleep in the natural sleep environment and/or when extended monitoring is clinically indicated. CHEST 2011; 139(6):1514-1527 C1 [Martin, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, North Hills, CA 91343 USA. [Martin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Hakim, Alex D.] Cedars Sinai Sleep Med Fellowship Program, Los Angeles, CA USA. RP Martin, JL (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr 11E, 16111 Plummer St, North Hills, CA 91343 USA. EM jennifer.martin@va.gov RI Martin, Jennifer/G-5217-2011 FU National Institutes of Health/National Institute on Aging [K23 AG028452]; VA RRD [IIR 1RX000135]; Cedars Sinai Sleep Medicine Fellowship Program; VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center; National Institutes of Health; Department of Veterans Affairs FX This work was supported by National Institutes of Health/National Institute on Aging K23 AG028452 (Dr Martin); VA RR&D IIR 1RX000135 (Dr Martin), Cedars Sinai Sleep Medicine Fellowship Program (Dr Hakim); and the VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center (Dr Martin).; Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Martin receives research funding from the National Institutes of Health and the Department of Veterans Affairs and presents educational workshops on the use of wrist actigraphy. Dr Hakim has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 85 TC 81 Z9 83 U1 5 U2 30 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2011 VL 139 IS 6 BP 1514 EP 1527 DI 10.1378/chest.10-1872 PG 14 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 776CC UT WOS:000291511100040 PM 21652563 ER PT J AU Green, JA Mor, MK Shields, AM Sevick, MA Palevsky, PM Fine, MJ Arnold, RM Weisbord, SD AF Green, Jamie A. Mor, Maria K. Shields, Anne Marie Sevick, Mary Ann Palevsky, Paul M. Fine, Michael J. Arnold, Robert M. Weisbord, Steven D. TI Prevalence and Demographic and Clinical Associations of Health Literacy in Patients on Maintenance Hemodialysis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID QUALITY-OF-LIFE; MANAGED CARE ENROLLEES; HOSPITAL ADMISSION; OVERLOOKED FACTOR; DIALYSIS PATIENTS; CHRONIC DISEASE; ADULT LITERACY; OLDER-ADULTS; DISPARITIES; POPULATION AB Background and objectives Although limited health literacy is estimated to affect over 90 million Americans and is recognized as an important public health concern, there have been few studies examining this issue in patients with chronic kidney disease. We sought to characterize the prevalence of and associations of demographic and clinical characteristics with limited health literacy in patients receiving maintenance hemodialysis. Design, setting, participants, & measurements As part of a prospective clinical trial of symptom management strategies in 288 patients treated with chronic hemodialysis, we assessed health literacy using the Rapid Estimate of Adult Literacy in Medicine (REALM). We defined limited health literacy as a REALM score and evaluated independent associations of demographic and baseline clinical characteristics with limited health literacy using multivariable logistic regression. Results Of the 260 patients who completed the REALM, 41 demonstrated limited health literacy. AfricanAmerican race, lower educational level, and veteran status were independently associated with limited health literacy. There was no association of limited health literacy with age, gender, serologic values, dialysis adequacy, overall symptom burden, quality of life, or depression. Conclusions Limited health literacy is common among patients receiving chronic hemodialysis. AfricanAmerican race and socioeconomic factors are strong independent predictors of limited health literacy. These findings can help inform the design and implementation of interventions to improve health literacy in the hemodialysis population. Clin J Am Soc Nephrol 6: 1354-1360, 2011. doi: 10.2215/gN.09761110 C1 [Green, Jamie A.; Palevsky, Paul M.; Weisbord, Steven D.] Univ Pittsburgh, Renal Electrolyte Div, Pittsburgh, PA 15261 USA. [Mor, Maria K.; Shields, Anne Marie; Sevick, Mary Ann; Fine, Michael J.; Weisbord, Steven D.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Palevsky, Paul M.; Weisbord, Steven D.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Sevick, Mary Ann; Fine, Michael J.; Arnold, Robert M.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Arnold, Robert M.] Univ Pittsburgh, Sect Palliat Care, Pittsburgh, PA USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. RP Green, JA (reprint author), Univ Pittsburgh, Renal Electrolyte Div, A915 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM greenja@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU Department of Veterans Affairs Health Research and Development Service [HSRD IIR 07-190]; American Kidney Fund FX This study was funded by a grant from the Department of Veterans Affairs Health Research and Development Service (Weisbord HSR&D IIR 07-190). These data were presented in abstract form at the 2009 annual meeting of the American Society of Nephrology. Dr. Green is supported by a grant from the American Kidney Fund Clinical Scientist in Nephrology Program. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 50 TC 29 Z9 29 U1 3 U2 10 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUN PY 2011 VL 6 IS 6 BP 1354 EP 1360 DI 10.2215/CJN.09761110 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 775YY UT WOS:000291500900019 PM 21551025 ER PT J AU Budisavljevic, MN Nietert, PJ Zhai, YS Dooley, MJ Rajagopalan, PR AF Budisavljevic, Milos N. Nietert, Paul J. Zhai, Yusheng Dooley, Mary J. Rajagopalan, P. R. TI Long-Term Effects of Kidney Donation on Renal Function and Blood Pressure in African Americans SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID FOLLOW-UP; DONORS; MICROALBUMINURIA; CONSEQUENCES; HYPERTENSION; PREVALENCE; AWARENESS; SURVIVAL; OUTCOMES; DISEASE AB Background and objectives African Americans (AAs) have four times higher prevalence of ESRD than Caucasians. Therefore, long-term effects of kidney donation are of considerable importance in this patient population. Design, setting, participants, & measurements GFR was measured by (125)I-iothalamate clearance, 24-hour urine albumin excretion, and 24-hour BP monitoring in 33 AAs and 11 CAs who donated kidneys for transplantation 5 to 23 years previously. Results Mean GFRs were 76 +/- 13 and 78 +/- 11 ml/min per 1.73 m(2) for AA and CA donors, respectively. Nine percent of the AA donors and none of the CA donors had GFRs below 60 ml/min per 1.73 m2. AA donors had a tendency for lower prevalence of microalbuminuria compared with CA donors (18.1% versus 36.3%) and a tendency for higher prevalence of macroalbuminuria compared with CAs (12.1% versus 0.0%). Twenty-four percent of the AAs, and 45% of the CAs were hypertensive with mean daytime BP >= 135/85 mmHg. Only 6% of AAs had a decrease in mean nocturnal systolic BP of 10% or more as compared with daytime readings. Older age at time of donation was associated (P = 0.046) with lower GFR values compared with younger ages. Conclusion Carefully selected AA kidney donors have well preserved renal function and a low prevalence of hypertension many years after kidney donation. Abnormal albumin excretion and loss of physiologic decrease in nocturnal BP is more prevalent in AA donors than the general AA population. Older age at donation may predict lower GFR after donation. Clin J Am Soc Nephrol 6: 1474-1480, 2011. doi: 10.2215/CJN.08240910 C1 [Budisavljevic, Milos N.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Rajagopalan, P. R.] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [Nietert, Paul J.; Zhai, Yusheng; Dooley, Mary J.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Budisavljevic, Milos N.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Budisavljevic, MN (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 171 Ashley Ave, Charleston, SC 29425 USA. EM Budisamn@musc.edu OI Nietert, Paul/0000-0002-3933-4986 FU Medical University of South Carolina Transplant Center, Dialysis Clinic Inc.; National Center for Research Resources [UL1RR029882] FX The project described was supported by the Medical University of South Carolina Transplant Center, Dialysis Clinic Inc., and Award Number UL1RR029882 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 24 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUN PY 2011 VL 6 IS 6 BP 1474 EP 1480 DI 10.2215/CJN.08240910 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 775YY UT WOS:000291500900033 PM 21551019 ER PT J AU Gutierrez, J Long, JA AF Gutierrez, Jennifer Long, Judith A. TI Reliability and validity of diabetes specific Health Beliefs Model scales in patients with diabetes and serious mental illness SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Diabetes; Serious mental illness; Health Beliefs Model ID GLYCEMIC CONTROL; MEDICATION ADHERENCE; MICROVASCULAR COMPLICATIONS; COGNITIVE DEFICITS; SCHIZOPHRENIA; VETERANS; OUTCOMES; LOCUS; UKPDS; CARE AB Aims: In this study we evaluate the reliability and validity of existing Health Beliefs Model (HBM) scales developed to assess HBM domains in a population of patients with both diabetes and serious mental illness (SMI). While diabetes medication adherence has frequently been evaluated through the lens of the HBM, it is unclear if developed scales are reliable and valid in patients with SMI. Methods: We surveyed 152 veterans with diabetes and SMI. Domains of the HBM assessed included perceived benefits, side effects and barriers to diabetes medication taking, perceived susceptibility to and severity of diabetes, diabetes self-efficacy, diabetes locus of control, and perceived diabetes control. Results: HBM scales showed good internal reliability within a SMI population, with Cronbach alphas ranging between 0.73 and 0.86 for all scales assessed except one. HBM scales also showed associations with self reported diabetes medication adherences in six of the ten domains. Conclusion: Scales assessing diabetes specific domains of the HBM exhibit both reliability and validity in patients with both diabetes and SMI. Published by Elsevier Ireland Ltd. C1 [Gutierrez, Jennifer; Long, Judith A.] Philadelphia VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Long, Judith A.] Univ Penn, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. [Long, Judith A.] Univ Penn, Diabet Endocrinol Res Ctr, Philadelphia, PA 19104 USA. [Long, Judith A.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Long, JA (reprint author), 1201 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM jalong@mail.med.upenn.edu FU University of Pennsylvania Diabetes Endocrine Research Center (DERC) [5-P30-DK-019525-33]; VA HSRD [IIR 07-124-3] FX Financial Sponsor: University of Pennsylvania Diabetes Endocrine Research Center (DERC) Pilot Grant 5-P30-DK-019525-33. VA HSR&D IIR 07-124-3. NR 32 TC 3 Z9 4 U1 3 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD JUN PY 2011 VL 92 IS 3 BP 342 EP 347 DI 10.1016/j.diabres.2011.02.018 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 775SR UT WOS:000291484200016 PM 21411173 ER PT J AU Gukovskaya, AS Gukovsky, I AF Gukovskaya, Anna S. Gukovsky, Ilya TI Which Way to Die: the Regulation of Acinar Cell Death in Pancreatitis by Mitochondria, Calcium, and Reactive Oxygen Species SO GASTROENTEROLOGY LA English DT Editorial Material ID PERMEABILITY TRANSITION; OXIDATIVE STRESS; NECROSIS; ACTIVATION; INJURY; NEUTROPHILS; MECHANISMS; APOPTOSIS; AUTOPHAGY; RELEASE C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Gukovskaya, AS (reprint author), W Angeles Healthcare Ctr, 11301 Wilshire Blvd,Blg 258,Rm 340, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu FU NIAAA NIH HHS [AA019730, P50 AA011999, P50AA11999, R01 AA019730]; NIDDK NIH HHS [DK059936, R01 DK059936] NR 36 TC 16 Z9 18 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2011 VL 140 IS 7 BP 1876 EP 1880 DI 10.1053/j.gastro.2011.04.025 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 774LR UT WOS:000291388200017 PM 21524653 ER PT J AU Agostoni, P Swenson, ER Bussotti, M Revera, M Meriggi, P Faini, A Lombardi, C Bilo, G Giuliano, A Bonacina, D Modesti, PA Mancia, G Parati, G AF Agostoni, Piergiuseppe Swenson, Erik R. Bussotti, Maurizio Revera, Miriam Meriggi, Paolo Faini, Andrea Lombardi, Carolina Bilo, Grzegorz Giuliano, Andrea Bonacina, Daniele Modesti, Pietro A. Mancia, Giuseppe Parati, Gianfranco CA HIGHCARE Investigators TI High-altitude exposure of three weeks duration increases lung diffusing capacity in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE hypoxia; respiration; heart failure; ventilation; oxygen ID PULMONARY GAS-EXCHANGE; CHRONIC HEART-FAILURE; CARBON-MONOXIDE; MAXIMAL EXERCISE; SEA-LEVEL; EDEMA; CO; RESIDENCE; OXYGEN; CARBOXYHEMOGLOBIN AB Background: high-altitude adaptation leads to progressive increase in arterial Pa-O2. In addition to increased ventilation, better arterial oxygenation may reflect improvements in lung gas exchange. Previous investigations reveal alterations at the alveolar-capillary barrier indicative of decreased resistance to gas exchange with prolonged hypoxia adaptation, but how quickly this occurs is unknown. Carbon monoxide lung diffusing capacity and its major determinants, hemoglobin, alveolar volume, pulmonary capillary blood volume, and alveolar-capillary membrane diffusion, have never been examined with early high-altitude adaptation. Methods and Results: lung diffusion was measured in 33 healthy lowlanders at sea level (Milan, Italy) and at Mount Everest South Base Camp (5,400 m) after a 9-day trek and 2-wk residence at 5,400 m. Measurements were adjusted for hemoglobin and inspired oxygen. Subjects with mountain sickness were excluded. After 2 wk at 5,400 m, hemoglobin oxygen saturation increased from 77.2 +/- 6.0 to 85.3 +/- 3.6%. Compared with sea level, there were increases in hemoglobin, lung diffusing capacity, membrane diffusion, and alveolar volume from 14.2 +/- 1.2 to 17.2 +/- 1.8 g/dl (P < 0.01), from 23.6 +/- 4.4 to 25.1 +/- 5.3 ml.min(-1).mmHg(-1) (P < 0.0303), 63 +/- 34 to 102 +/- 65 ml.min(-1).mmHg(-1) (P < 0.01), and 5.6 +/- 1.0 to 6.3 +/- 1.1 liters (P < 0.01), respectively. Pulmonary capillary blood volume was unchanged. Membrane diffusion normalized for alveolar volume was 10.9 +/- 5.2 at sea level rising to 16.0 +/- 9.2 ml.min(-1).mmHg(-1).l(-1) (P < 0.01) at 5,400 m. Conclusions: at high altitude, lung diffusing capacity improves with acclimatization due to increases of hemoglobin, alveolar volume, and membrane diffusion. Reduction in alveolar-capillary barrier resistance is possibly mediated by an increase of sympathetic tone and can develop in 3 wk. C1 [Agostoni, Piergiuseppe] IRCCS, Ctr Cardiol Monzino, Milan, Italy. [Agostoni, Piergiuseppe] Univ Milan, Dipartimento Sci Cardiovasc, Milan, Italy. [Agostoni, Piergiuseppe; Swenson, Erik R.] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Bussotti, Maurizio] IRCCS, Fdn S Maugeri, Milan, Italy. [Revera, Miriam; Meriggi, Paolo; Faini, Andrea; Lombardi, Carolina; Bilo, Grzegorz; Giuliano, Andrea; Bonacina, Daniele; Parati, Gianfranco] S Luca Hosp, Ist Auxol Italiano, Dept Cardiol, Milan, Italy. [Lombardi, Carolina; Mancia, Giuseppe] Univ Milano Bicocca, Dept Clin Med & Prevent, Milan, Italy. [Modesti, Pietro A.] Univ Florence, Dipartimento Area Crit Med Chirurg, Florence, Italy. [Modesti, Pietro A.] IRCCS, Ctr Santa Maria Ulivi Pozzolat, Fdn Don C Gnocchi, San Giovanni Rotondo, Italy. RP Agostoni, P (reprint author), IRCCS, Ctr Cardiol Monzino, Milan, Italy. EM piergiuseppe.agostoni@unimi.it RI Meriggi, Paolo/F-8444-2011; Modesti, Pietro Amedeo/B-2638-2012; Bilo, Grzegorz/J-8694-2016 OI Modesti, Pietro Amedeo/0000-0002-9511-2173; Bilo, Grzegorz/0000-0002-5104-9176; Revera, Miriam/0000-0002-3388-1858; Parati, Gianfranco/0000-0001-9402-7439; Faini, Andrea/0000-0002-8924-8234 FU Boehringer-Ingelheim (Germany); Banca Intesa San Paolo (Italy) FX The HIGHCARE project was financed by Boehringer-Ingelheim (Germany) and Banca Intesa San Paolo (Italy) unrestricted grants. NR 53 TC 17 Z9 18 U1 1 U2 20 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 JUN PY 2011 VL 110 IS 6 BP 1564 EP 1571 DI 10.1152/japplphysiol.01167.2010 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 776KG UT WOS:000291532600011 PM 21436463 ER PT J AU Elkassabany, NM Mandel, JE AF Elkassabany, Nabil M. Mandel, Jeff E. TI Con: A General Anesthesiologist With a Certain Skill Set Is Qualified to Provide Services in the Interventional Cardiology and Electrophysiology Laboratory SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE cardiac electrophysiology; heart catheterization; anesthesia; general anesthesia; anesthesia and sedation C1 [Elkassabany, Nabil M.] Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Elkassabany, NM (reprint author), Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia VA Med Ctr, 3400 Spruce St,Dulles 6, Philadelphia, PA 19104 USA. EM Nabil.elkassabany@uphs.upenn.edu RI Mandel, Jeff/D-1128-2009 OI Mandel, Jeff/0000-0002-8846-4154 NR 12 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD JUN PY 2011 VL 25 IS 3 BP 557 EP 558 DI 10.1053/j.jvca.2011.03.007 PG 2 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 774UL UT WOS:000291412000028 PM 21621159 ER PT J AU Rowe, LS Doss, BD Hsueh, AC Libet, J Mitchell, AE AF Rowe, Lorelei Simpson Doss, Brian D. Hsueh, Annie C. Libet, Julian Mitchell, Alexandra E. TI Coexisting Difficulties and Couple Therapy Outcomes: Psychopathology and Intimate Partner Violence SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE couple therapy; relationship satisfaction; psychopathology; intimate partner violence; marriage ID MARITAL SATISFACTION; QUALITY AB Couples presenting for treatment of relationship distress often experience additional problems, including individual psychopathology and intimate partner violence (IPV). Both issues are associated with current and future poor relationship functioning in nontreatment samples, but relatively little is understood about their association with initial presentation and outcomes in couple therapy. The current study examined these associations in a sample of 177 heterosexual couples who received therapy at two Veteran's Affairs clinics. Unlike most studies of couple therapy outcomes, couples were not excluded from treatment specifically because of high levels of psychopathology or IPV. Results of Actor Partner Interdependence Model (APIM) analyses revealed actor and partner effects of depression, actor effects of anxiety, and partner effects of IPV on initial relationship satisfaction, such that greater coexisting difficulties were associated with poorer initial satisfaction. However, improvement in relationship satisfaction over the course of therapy was not associated with psychopathology, and, contrary to hypothesis, was positively associated with men's IPV prior to treatment, even when initial level of satisfaction was controlled. The results suggest that coexisting symptoms of psychopathology or IPV may not necessarily interfere with therapy outcomes and, indeed, therapy may have positive effects for couples with these problems. C1 [Rowe, Lorelei Simpson; Mitchell, Alexandra E.] So Methodist Univ, Dept Psychol, Dallas, TX 75275 USA. [Doss, Brian D.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Hsueh, Annie C.] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. [Libet, Julian] Ralph H Johnson VA Med Ctr, Psychol Serv, Charleston, SC USA. RP Rowe, LS (reprint author), So Methodist Univ, Dept Psychol, POB 750442, Dallas, TX 75275 USA. EM lsimpson@smu.edu NR 8 TC 4 Z9 4 U1 1 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD JUN PY 2011 VL 25 IS 3 BP 455 EP 458 DI 10.1037/a0023696 PG 4 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 776AS UT WOS:000291507500015 PM 21534671 ER PT J AU Apfel, BA Otte, C Inslicht, SS McCaslin, SE Henn-Haase, C Metzler, TJ Makotkine, I Yehuda, R Neylan, TC Marmar, CR AF Apfel, Brigitte A. Otte, Christian Inslicht, Sabra S. McCaslin, Shannon E. Henn-Haase, Clare Metzler, Thomas J. Makotkine, Iouri Yehuda, Rachel Neylan, Thomas C. Marmar, Charles R. TI Pretraumatic prolonged elevation of salivary MHPG predicts peritraumatic distress and symptoms of post-traumatic stress disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Neuroendocrinology; Post-traumatic stress disorder; Stress test; Salivary MHPG; Prospective study; Police ID HEART-RATE; PSYCHOLOGICAL STRESS; PTSD SYMPTOMS; PSYCHOBIOLOGICAL RESPONSES; PSYCHOMETRIC PROPERTIES; EMERGENCY-DEPARTMENT; CHILDHOOD TRAUMA; MEMORY STORAGE; PLASMA-LEVELS; NOREPINEPHRINE AB Post-traumatic stress disorder (PTSD) is associated with elevated catecholamines and increased sympathetic arousal. However, it is unknown whether this condition is a pre-existing vulnerability factor for PTSD or an acquired result of either trauma exposure or the development of FTSD symptoms. We sought to examine if salivary 3-methoxy-4-hydroxy-phenylglycol (MHPG) in response to a laboratory stressor prior to critical incident exposure predicts the development of PTSD symptoms and if early childhood trauma influences this relationship. In a prospective cohort study, 349 urban police officers were assessed during academy training (baseline) and 243 were reassessed 12 months after the start of active duty (follow-up). At baseline, participants observed a video consisting of police critical incidents. Salivary MHPG was measured before and immediately after the challenge, and after 20 min recovery. At follow-up, peritraumatic distress and PTSD symptoms were assessed in relationship to the worst critical incident during the past year. Participants with childhood trauma showed a trend towards higher MHPG increase to the challenge. Higher MHPG levels after 20 min recovery were associated with both higher levels of peritraumatic distress and PTSD symptoms at follow-up. In a path analysis, elevated MHPG levels predicted higher peritraumatic distress which in turn predicted higher levels of PTSD symptoms while the direct effect of elevated MHPG levels on PTSD symptoms was no longer significant. Prolonged elevation of salivary MHPG in response to a laboratory stressor marks a predisposition to experience higher levels of peritraumatic distress and subsequently more PTSD symptoms following critical incident exposure. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Apfel, Brigitte A.; Inslicht, Sabra S.; McCaslin, Shannon E.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Apfel, Brigitte A.; Inslicht, Sabra S.; McCaslin, Shannon E.; Metzler, Thomas J.; Neylan, Thomas C.] Vet Affairs Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA. [Otte, Christian] Univ Hosp Hamburg Eppendorf, Dept Psychiat, Hamburg, Germany. [Makotkine, Iouri; Yehuda, Rachel] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Henn-Haase, Clare; Marmar, Charles R.] NYU, Dept Psychiat, New York, NY 10016 USA. RP Apfel, BA (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, 116D,4150 Clement St, San Francisco, CA 94121 USA. EM brigitte.apfel@ucsf.edu FU Glaxo Smith Kline; Actelion; NIMH [5R01-MH056350-10] FX Dr. Neylan has served on the Pfizer-Advisory Panel and received research support from Glaxo Smith Kline and Actelion. Dr. Marmar has served on the Pfizer-Advisory Panel. All other authors declare that they have no conflicts of interest.; Funding for this study was provided by NIMH Grant 5R01-MH056350-10; the NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 67 TC 9 Z9 9 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JUN PY 2011 VL 45 IS 6 BP 735 EP 741 DI 10.1016/j.jpsychires.2010.11.016 PG 7 WC Psychiatry SC Psychiatry GA 776XH UT WOS:000291573400004 PM 21196013 ER PT J AU Goodman, M Hazlett, EA Avedon, JB Siever, DR Chu, KW New, AS AF Goodman, Marianne Hazlett, Erin A. Avedon, Jennifer B. Siever, Daniel R. Chu, King-Wai New, Antonia S. TI Anterior cingulate volume reduction in adolescents with borderline personality disorder and co-morbid major depression SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Borderline personality disorder; Adolescent; Structural neuroimaging; MRI; anterior cingulate; Major depression ID CORTEX; AGGRESSION; SYMPTOMS; OUTCOMES; MATTER; GRAY; MRI AB Borderline Personality Disorder (BPD) is a serious illness characterized by emotional dysregulation, impulsivity, and impaired interpersonal relationships. Prior work shows the anterior cingulate gyrus (ACG)-a region primarily involved in assessing the salience of emotional information and regulating emotional responses-is smaller in adults with BPD. We tested the hypothesis that, similar to adults, adolescents with BPD would have reduced Brodmann area (BA)-24 volume. Thirteen adolescent inpatients with co-morbid BPD and Major Depressive Disorder (MDD) and 13 matched healthy controls received 3T-MRI scans. Using a cytoarchitecturally-derived approach measuring gray and white matter volume, we observed a Group x Cingulate BA (25,24,31,23,29) x Matter (gray, white) type interaction indicating the BPD/MDD adolescents had smaller BA24 volume in gray but not white matter. Greater number of suicide attempts and BPD symptom severity measured by the Diagnostic Interview for BPD-revised (DIB-R) total score but not depressive symptoms measured by the Beck Depression Inventory (BDI) was associated with smaller BA24 volume. Our preliminary findings suggest that BPD-related abnormalities in BA24 volume may occur early in the developmental course of BPD with MDD. Future studies examining samples of MDD patients with and without BPD co-morbidity will be needed to clarify whether BA24 volume reductions are specific to BPD. Published by Elsevier Ltd. C1 [Goodman, Marianne; Hazlett, Erin A.; Avedon, Jennifer B.; New, Antonia S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Goodman, M (reprint author), James J Peters Dept Vet Adm Med Ctr, 130 W Kingsbridge Rd,Off 3B-20B, Bronx, NY 10468 USA. EM Marianne.goodman@va.gov FU VA; NIMH [R01MH073911]; National Center for Research Resources (NCRR) [M01-Patient Care RR-0071]; Mental Illness Research and ClinicalCenter; VISN 3 Veterans Heath Administration FX This work was supported by a VA Career Development grant to MG and NIMH grant R01MH073911 to EAH. Other support came from grant M01-Patient Care RR-0071 from the National Center for Research Resources (NCRR) and the Mental Illness Research and ClinicalCenter, VISN 3 Veterans Heath Administration. These funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 27 TC 31 Z9 31 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JUN PY 2011 VL 45 IS 6 BP 803 EP 807 DI 10.1016/j.jpsychires.2010.11.011 PG 5 WC Psychiatry SC Psychiatry GA 776XH UT WOS:000291573400013 PM 21145068 ER PT J AU Newgard, CD Nelson, MJ Kampp, M Saha, S Zive, D Schmidt, T Daya, M Jui, J Wittwer, L Warden, C Sahni, R Stevens, M Gorman, K Koenig, K Gubler, D Rosteck, P Lee, J Hedges, JR AF Newgard, Craig D. Nelson, Maria J. Kampp, Michael Saha, Somnath Zive, Dana Schmidt, Terri Daya, Mohamud Jui, Jonathan Wittwer, Lynn Warden, Craig Sahni, Ritu Stevens, Mark Gorman, Kyle Koenig, Karl Gubler, Dean Rosteck, Pontine Lee, Jan Hedges, Jerris R. TI Out-of-Hospital Decision Making and Factors Influencing the Regional Distribution of Injured Patients in a Trauma System SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 10th Annual Academic Emergency Medicine Consensus Conference/Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY 13, 2009 CL New Orleans, LA SP Soc Acad Emergency Med DE Triage; Cognitive reasoning; Emergency medical services; Trauma ID EMERGENCY MEDICAL-SERVICES; PARAMEDIC JUDGMENT; PROBABILISTIC LINKAGE; NATIONAL EVALUATION; FIELD TRIAGE; MORTALITY; SEVERITY; THINKING; CARE AB Background: The decision-making processes used for out-of-hospital trauma triage and hospital selection in regionalized trauma systems remain poorly understood. The objective of this study was to assess the process of field triage decision making in an established trauma system. Methods: We used a mixed methods approach, including emergency medical services (EMS) records to quantify triage decisions and reasons for hospital selection in a population-based, injury cohort (2006-2008), plus a focused ethnography to understand EMS cognitive reasoning in making triage decisions. The study included 10 EMS agencies providing service to a four-county regional trauma system with three trauma centers and 13 nontrauma hospitals. For qualitative analyses, we conducted field observation and interviews with 35 EMS field providers and a round table discussion with 40 EMS management personnel to generate an empirical model of out-of-hospital decision making in trauma triage. Results: A total of 64,190 injured patients were evaluated by EMS, of whom 56,444 (88.0%) were transported to acute care hospitals and 9,637 (17.1% of transports) were field trauma activations. For nontrauma activations, patient/family preference and proximity accounted for 78% of destination decisions. EMS provider judgment was cited in 36% of field trauma activations and was the sole criterion in 23% of trauma patients. The empirical model demonstrated that trauma triage is driven primarily by EMS provider "gut feeling" (judgment) and relies heavily on provider experience, mechanism of injury, and early visual cues at the scene. Conclusions: Provider cognitive reasoning for field trauma triage is more heuristic than algorithmic and driven primarily by provider judgment, rather than specific triage criteria. C1 [Newgard, Craig D.; Nelson, Maria J.; Kampp, Michael; Zive, Dana; Schmidt, Terri; Daya, Mohamud; Jui, Jonathan; Warden, Craig; Sahni, Ritu] Oregon Hlth & Sci Univ, Dept Emergency Med, Ctr Policy & Res Emergency Med, Portland, OR 97239 USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. [Schmidt, Terri] Clackamas Cty Amer Med Response, Clackamas, OR USA. [Daya, Mohamud; Stevens, Mark] Tualatin Valley Fire & Rescue, Aloha, OR USA. [Jui, Jonathan] Multnomah Cty Emergency Med Serv, Multnomah Cty Hlth Dept, Portland, OR USA. [Wittwer, Lynn] Clark Cty Emergency Med Serv, Vancouver, WA USA. [Warden, Craig; Gorman, Kyle; Koenig, Karl] Clackamas Cty Fire Dist 1, Clackamas, OR USA. [Sahni, Ritu] EMS & Trauma Syst, Oregon Dept Human Serv, Publ Hlth Div, Portland, OR USA. [Gubler, Dean] Legacy Emanuel Trauma Program, Portland, OR USA. [Rosteck, Pontine] NW Amer Med Response, Portland, OR USA. [Lee, Jan] Metrowest Ambulance, Hillsboro, OR USA. [Hedges, Jerris R.] Univ Hawaii Manoa, Dept Med, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Newgard, CD (reprint author), Oregon Hlth & Sci Univ, Dept Emergency Med, Ctr Policy & Res Emergency Med, 3181 SW Sam Jackson Pk Rd,Mail Code CR-114, Portland, OR 97239 USA. EM newgardc@ohsu.edu FU NCRR NIH HHS [UL1 RR024140, UL1 RR024140-01]; NIMHD NIH HHS [U54 MD007584] NR 30 TC 22 Z9 22 U1 1 U2 6 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 JUN PY 2011 VL 70 IS 6 BP 1345 EP 1353 DI 10.1097/TA.0b013e3182191a1b PG 9 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 775QR UT WOS:000291478500013 PM 21817971 ER PT J AU Danczyk, RC Mitchell, EL Kryger, SG Burk, C Singh, S Liem, TK Landry, GJ Edwards, JM Petersen, BD Moneta, GL AF Danczyk, Rachel C. Mitchell, Erica L. Kryger, Sharon G. Burk, Chad Singh, Sarguni Liem, Timothy K. Landry, Gregory J. Edwards, James M. Petersen, Bryan D. Moneta, Gregory L. TI Comparing Patency and Salvage Rates between Multiple Ipsilateral Iliac Artery Stents and Isolated Iliac Artery Stents: Beyond TASC II SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 16-18, 2011 CL Chicago, IL SP Soc Vasc Surg C1 [Danczyk, Rachel C.; Mitchell, Erica L.; Kryger, Sharon G.; Burk, Chad; Singh, Sarguni; Liem, Timothy K.; Landry, Gregory J.; Moneta, Gregory L.] Oregon Hlth & Sci Univ, Div Vasc Surg, Portland, OR 97201 USA. [Edwards, James M.] Portland VA Med Ctr, Portland, OR USA. [Petersen, Bryan D.] Oregon Hlth & Sci Univ, Dotter Inst, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2011 VL 53 SU S BP 63S EP 63S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 774TY UT WOS:000291410700120 ER PT J AU Hernandez-Davies, JE Zape, JP Landaw, EM Tan, XL Presnell, A Griffith, D Heinrich, MC Glaser, KB Sakamoto, KM AF Hernandez-Davies, Jenny E. Zape, Joan P. Landaw, Elliot M. Tan, Xiaolin Presnell, Ajia Griffith, Diana Heinrich, Michael C. Glaser, Keith B. Sakamoto, Kathleen M. TI The Multitargeted Receptor Tyrosine Kinase Inhibitor Linifanib (ABT-869) Induces Apoptosis through an Akt and Glycogen Synthase Kinase 3 beta-Dependent Pathway SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID LEUKEMIC-CELLS; DOWN-REGULATION; AML CELLS; FLT3; ACTIVATION; MCL-1; PHOSPHORYLATION; TRANSFORMATION; DAUNORUBICIN; CYTARABINE AB The FMS-like receptor tyrosine kinase 3 (FLT3) plays an important role in controlling differentiation and proliferation of hematopoietic cells. Activating mutations in FLT3 occur in patients with acute myeloid leukemia (AML; 15%-35%), resulting in abnormal cell proliferation. Furthermore, both adult and pediatric patients with AML harboring the FLT3 internal tandem duplication (ITD) mutation have a poor prognosis. Several inhibitors have been developed to target mutant FLT3 for the treatment of AML, yet the molecular pathways affected by drug inhibition of the mutated FLT3 receptor alone have not been characterized as yet. Linifanib (ABT-869) is a multitargeted tyrosine kinase receptor inhibitor that suppresses FLT3 signaling. In this article, we show that treatment with linifanib inhibits proliferation and induces apoptosis in ITD mutant cells in vitro and in vivo. We show that treatment with linifanib reduces phosphorylation of Akt and glycogen synthase kinase 3 beta (GSK3 beta). In addition, we show that inhibition of GSK3b decreases linifanib-induced apoptosis. This study shows the importance of GSK3 beta as a potential target for AML therapy, particularly in patients with FLT3 ITD mutations. Mol Cancer Ther; 10(6); 949-59. (C)2011 AACR. C1 [Hernandez-Davies, Jenny E.; Zape, Joan P.; Sakamoto, Kathleen M.] Univ Calif Los Angeles, Mattel Childrens Hosp UCLA, Jonsson Comprehens Canc Ctr, Div Hematol Oncol,Gwynne Hazen Cherry Mem Labs, Los Angeles, CA 90095 USA. [Hernandez-Davies, Jenny E.; Sakamoto, Kathleen M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Sakamoto, Kathleen M.] Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA 90095 USA. [Sakamoto, Kathleen M.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. [Landaw, Elliot M.] Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA 90095 USA. [Tan, Xiaolin] Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine, CA 92717 USA. [Presnell, Ajia; Griffith, Diana; Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR USA. [Presnell, Ajia; Griffith, Diana; Heinrich, Michael C.] OHSU Knight Canc Inst, Portland, OR USA. [Glaser, Keith B.] Abbott Labs, Abbott Pk, IL 60064 USA. RP Sakamoto, KM (reprint author), Univ Calif Los Angeles, Mattel Childrens Hosp UCLA, Jonsson Comprehens Canc Ctr, Div Hematol Oncol,Gwynne Hazen Cherry Mem Labs, Los Angeles, CA 90095 USA. EM ksakamoto@mednet.ucla.edu FU Abbott Laboratories, Inc.; Genentech, Inc.; NIH [HL75826, HL83077]; William Lawrence and Blanche Hughes Foundation; St. Baldrick's Foundation; Department of Veterans Affairs; Leukemia and Lymphoma Society FX K.M. Sakamoto received a commercial research grant from Abbott Laboratories, Inc., and received other commercial research support from Genentech, Inc. M.C. Heinrich has equity interest in Molecular M.D.; K.M. Sakamoto is supported by NIH grants HL75826 and HL83077, the William Lawrence and Blanche Hughes Foundation, and the St. Baldrick's Foundation. K.M. Sakamoto is a scholar of the Leukemia and Lymphoma Society. M.C. Heinrich is supported, in part, by a Merit Review grant from the Department of Veterans Affairs and a SCOR grant from the Leukemia and Lymphoma Society. NR 34 TC 11 Z9 13 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUN PY 2011 VL 10 IS 6 BP 949 EP 959 DI 10.1158/1535-7163.MCT-10-0904 PG 11 WC Oncology SC Oncology GA 775AI UT WOS:000291428000004 PM 21471285 ER PT J AU Ringman, JM Taylor, K Teng, E Coppola, G Gylys, K AF Ringman, J. M. Taylor, K. Teng, E. Coppola, G. Gylys, K. TI LONGITUDINAL CHANGE IN CSF BIOMARKERS IN A PRESYMPTOMATIC CARRIER OF AN APP MUTATION SO NEUROLOGY LA English DT Editorial Material ID ALZHEIMER-DISEASE; MARKERS C1 [Ringman, J. M.] Univ Calif Los Angeles, Mary S Easton Ctr Alzheimers Dis Res, Dept Neurol, Los Angeles, CA 90095 USA. [Taylor, K.; Gylys, K.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90095 USA. [Teng, E.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Ringman, JM (reprint author), Univ Calif Los Angeles, Mary S Easton Ctr Alzheimers Dis Res, Dept Neurol, 10911 Weyburn Ave,200, Los Angeles, CA 90095 USA. EM jringman@mednet.ucla.edu FU NCATS NIH HHS [UL1 TR000124]; NCRR NIH HHS [M01-RR00865, UL1 RR033176]; NIA NIH HHS [P50 AG-16570, K08 AG-22228] NR 7 TC 10 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2011 VL 76 IS 24 BP 2124 EP 2125 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 777BR UT WOS:000291588800018 PM 21562250 ER PT J AU Traugott, KA Echevarria, K Maxwell, P Green, K Lewis, JS AF Traugott, Kristi A. Echevarria, Kelly Maxwell, Pamela Green, Kay Lewis, James S., II TI Monotherapy or Combination Therapy? The Pseudomonas aeruginosa Conundrum SO PHARMACOTHERAPY LA English DT Review DE Pseudomonas aeruginosa; combination therapy; bacteremia; ventilator-associated pneumonia; monotherapy ID VENTILATOR-ASSOCIATED PNEUMONIA; BLOOD-STREAM INFECTIONS; BETA-LACTAM MONOTHERAPY; GRAM-NEGATIVE BACTEREMIA; INTENSIVE-CARE UNITS; ANTIMICROBIAL THERAPY; ANTIBIOTIC-THERAPY; TIME-KILL; RETROSPECTIVE ANALYSIS; STAPHYLOCOCCUS-AUREUS AB The use of combination antibiotic therapy for severe pseudomonal infections is a standard practice in many hospitals; however, the data supporting its use are somewhat unclear. Possible benefits of combination therapy for Pseudomonas aeruginosa infections include in vitro antibiotic synergy, prevention of the emergence of bacterial resistance while receiving therapy, and improved adequacy of empiric therapy. Unfortunately, the potential disadvantages are also considerable, the most worrisome of which are drug toxicity and creation of multidrug-resistant organisms in the environment. Many in vitro and animal studies have attempted to shed light on this clinically challenging issue; however, these studies have often yielded conflicting results and used different study methods, which limits the clinical utility of the results. Clinical studies have also attempted to clarify this issue, particularly in patients with serious pseudomonal infections such as bacteremia and ventilator-associated pneumonia, but again, often resulted in conflicting conclusions. Thus, we performed a MEDLINE search (1950-May 2010) of clinical and in vitro studies evaluating the use of antibiotic combination therapy and monotherapy for bacteremia and pneumonia due to P. aeruginosa. Although a clear answer still eludes this controversy, combination therapy for seriously ill patients suspected of having pseudomonal infection has been shown, with considerable evidence, to improve the likelihood of an active agent being included in the initial antibiotic regimen of these patients. The clinical status of the patient and true likelihood of encountering a multidrug-resistant organism should be evaluated before deciding on empiric combination therapy. Future research may be able to better identify which patient populations might receive the most benefit from combination therapy rather than using combination therapy for everyone at risk for these infections. C1 [Maxwell, Pamela; Green, Kay; Lewis, James S., II] Univ Hlth Syst, Dept Pharm Serv, San Antonio, TX 78229 USA. [Echevarria, Kelly] S Texas Vet Hlth Care Syst, Dept Pharm Serv, San Antonio, TX USA. [Traugott, Kristi A.] Ochsner Med Ctr, Dept Pharm Serv, New Orleans, LA USA. RP Lewis, JS (reprint author), Univ Hlth Syst, Dept Pharm Serv, 4502 Med Dr,MS 102-1, San Antonio, TX 78229 USA. EM James.Lewis@uhs-sa.com NR 57 TC 28 Z9 29 U1 0 U2 12 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JUN PY 2011 VL 31 IS 6 BP 598 EP 608 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774HE UT WOS:000291375500009 PM 21923444 ER PT J AU Grudzen, CR Meeker, D Torres, JM Du, QL Morrison, RS Andersen, RM Gelberg, L AF Grudzen, Corita R. Meeker, Daniella Torres, Jacqueline M. Du, Qingling Morrison, R. Sean Andersen, Ronald M. Gelberg, Lillian TI Comparison of the Mental Health of Female Adult Film Performers and Other Young Women in California SO PSYCHIATRIC SERVICES LA English DT Article ID GREATER SYDNEY AREA; SEX WORKERS; SUBSTANCE-ABUSE; PUBLIC-HEALTH; LOS-ANGELES; VIOLENCE; INFECTIONS; DEPRESSION; OCCUPATION; INDUSTRY AB Objective: This study compared self-reported mental health status and current depression of female adult film performers and other young women. Methods: A cross-sectional structured online survey adapted from the California Women's Health Survey (CWHS) was self-administered to a convenience sample of 134 current female adult film performers via the Internet. Bivariate and multivariate analyses were used to compare data for these women with data for 1,773 women of similar ages who responded to the 2007 CWHS. Main outcome measures were self-reported mental health status, measured with the Behavioral Risk Factor Surveillance Survey core-instrument quality-of-life questions, and current depression, measured with the Patient Health Questionnaire-8. Results: Performers reported a mean of 7.2 days of poor mental health in the past 30 days, compared with 4.8 days for CWHS respondents, and 33% met criteria for current depression, compared with 13% of CWHS respondents (p<.01). As children, the adult film performers were more likely to have been victims of forced sex (37% compared with 13% of CWHS respondents), to have lived in poverty (24% and 12%), and to have been placed in foster care (21% and 4%) (p<.01). In the past 12 months, 50% of the performers reported living in poverty and 34% reported experiencing domestic violence, compared with 36% and 6%, respectively, of CWHS respondents (p<.01). As adults, 27% had experienced forced sex, compared with 9% of CWHS respondents (p<.01). Conclusions: Female adult film performers have significantly worse mental health and higher rates of depression than other California women of similar ages. (Psychiatric Services 62: 639-645, 2011) C1 [Grudzen, Corita R.] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Grudzen, Corita R.; Du, Qingling; Morrison, R. Sean] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Morrison, R. Sean] James J Peters VA Med Ctr, Bronx, NY USA. [Meeker, Daniella] RAND Corp, Santa Monica, CA USA. [Torres, Jacqueline M.; Andersen, Ronald M.; Gelberg, Lillian] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Gelberg, Lillian] Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA USA. RP Grudzen, CR (reprint author), Mt Sinai Sch Med, Dept Emergency Med, 1 Gustave Levy Pl,Box 1620, New York, NY 10029 USA. EM corita.grudzen@mssm.edu OI Meeker, Daniella/0000-0002-1034-7628; Grudzen, Corita/0000-0003-3039-8497 FU University of California Office of the President; National Institute on Aging [K24 AG022345] FX This project was supported by an Innovative, Developmental, Exploratory Award (IDEA) from the California HIV/AIDS Research Program, University of California Office of the President. The funding entity had no role in the design and conduct of the study; collection, management, analysis, and interpretation of data; and preparation, review, or approval of the manuscript. Dr. Morrison was supported by a Mid-Career Investigator Award in Patient Oriented Research (K24 AG022345) from the National Institute on Aging. The authors thank the California Women's Health Survey Work-group for providing access to the 2007 CWHS data set. NR 44 TC 3 Z9 3 U1 3 U2 7 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 JUN PY 2011 VL 62 IS 6 BP 639 EP 645 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 774SL UT WOS:000291406600012 PM 21632733 ER PT J AU Basham, C Denneson, LM Millet, L Shen, X Duckart, J Dobscha, SK AF Basham, Chandra Denneson, Lauren M. Millet, Lisa Shen, Xun Duckart, Jonathan Dobscha, Steven K. TI Characteristics and VA Health Care Utilization of U.S. Veterans Who Completed Suicide in Oregon Between 2000 and 2005 SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID DEATH REPORTING SYSTEM; MENTAL-HEALTH; PHYSICAL ILLNESS; FIREARM SUICIDE; MARITAL-STATUS; DEPRESSION; AFFAIRS; VALIDITY; PREDICTORS; PREVENTION AB Oregon Violent Death Reporting System data were linked with Veterans Affairs (VA) administrative data to identify and describe veterans who completed suicide in Oregon from 2000 to 2005 (n = 968), and to describe their VA health care utilization in the year prior to death. Twenty-two percent had received health care in the VA system. Of these, 57% did not have mental health diagnoses and 58% had not seen mental health professionals. A larger proportion of those who accessed care were VA-enrolled and received service-connected disability benefits. Fifty-five veterans were hospitalized during the year prior to death. Of these, 33% completed suicide within 30 days of a hospitalization. Further development of suicide prevention strategies for veterans in the community, including general medical treatment settings, is indicated. C1 [Denneson, Lauren M.; Duckart, Jonathan; Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Phys & Mental D, Portland, OR 97207 USA. [Basham, Chandra] ZoomCare PC, Hillsboro, OR USA. [Denneson, Lauren M.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Millet, Lisa; Shen, Xun] Oregon Publ Hlth Div, Portland, OR USA. RP Denneson, LM (reprint author), Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Phys & Mental D, POB 1034 P3DEP PC, Portland, OR 97207 USA. EM lauren.denneson@va.gov NR 33 TC 9 Z9 9 U1 2 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0363-0234 J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD JUN PY 2011 VL 41 IS 3 BP 287 EP 296 DI 10.1111/j.1943-278X.2011.00028.x PG 10 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 774OG UT WOS:000291395300004 PM 21463353 ER PT J AU Albasanz-Puig, A Murray, J Preusch, M Coan, D Namekata, M Patel, Y Dong, ZM Rosenfeld, ME Wijelath, ES AF Albasanz-Puig, Adaia Murray, Jacqueline Preusch, Michael Coan, Daniel Namekata, Mayumi Patel, Yatin Dong, Zhao Ming Rosenfeld, Michael E. Wijelath, Errol S. TI Oncostatin M is expressed in atherosclerotic lesions: A role for Oncostatin M in the pathogenesis of atherosclerosis SO ATHEROSCLEROSIS LA English DT Article DE Oncostatin M; Smooth muscle cell; Atherosclerosis; Carotid plaques; ApoE(-/-); STAT-1; STAT-3 ID SMOOTH-MUSCLE-CELLS; IN-VITRO; ENDOTHELIAL-CELLS; SIGNALING PATHWAY; CAROTID PLAQUE; ED-B; ANGIOGENESIS; INDUCTION; CYTOKINES; DISEASE AB Objective: Chronic inflammation plays a pivotal role in the development and progression of atherosclerosis. The inflammatory response is mediated by cytokines. The aim of this study was to determine if OncostatinM(OSM), a monocyte and T-lymphocyte specific cytokine is present in atherosclerotic lesions. We also investigated the roles of signal transducer and activator of transcription (STAT)-1 and STAT-3 in regulating OSM-induced smooth muscle cell (SMC) proliferation, migration and cellular fibronectin (cFN) synthesis. Methods and results: Immunostaining of atherosclerotic lesions from human carotid plaques demonstrated the expression of OSM antigen in both macrophages and SMCs. Explanted SMCs from human carotid plaques expressed OSM mRNA and protein as determined by RT-PCR and Western blotting. Using the chow-fed ApoE-/- mouse model of atherosclerosis, we observed that OSM was initially expressed in the intima at 20 weeks of age. By 30 weeks, OSM was expressed in both the intima and media. In vitro studies show that OSM promotes SMC proliferation, migration and cFN synthesis. Lentivirus mediated-inhibition of STAT-1 and STAT-3 prevented OSM-induced SMC proliferation, migration and cellular fibronectin synthesis. Conclusions: These findings demonstrate that OSM is expressed in atherosclerotic lesions and may contribute to the progression of atherosclerosis by promoting SMC proliferation, migration and extracellular matrix protein synthesis through the STAT pathway. Published by Elsevier Ireland Ltd. C1 [Preusch, Michael; Dong, Zhao Ming; Rosenfeld, Michael E.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Albasanz-Puig, Adaia; Murray, Jacqueline; Coan, Daniel; Namekata, Mayumi; Dong, Zhao Ming; Wijelath, Errol S.] VA Puget Sound Hlth Care Syst, Dept Surg, Div Vasc Surg, Seattle, WA USA. [Patel, Yatin] Kings Coll London, Sch Med London, Div Cardiovasc, Dept Cardiol, London, England. RP Wijelath, ES (reprint author), Dept Vet Affairs Med Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM errolw@u.washington.edu FU U.S. Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory FX This study was supported by the U.S. Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory Research Program. We thank Dr. Michael Sobel for providing carotid endarterectomy specimens and for critical review of the manuscript. NR 40 TC 18 Z9 20 U1 0 U2 4 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 JUN PY 2011 VL 216 IS 2 BP 292 EP 298 DI 10.1016/j.atherosclerosis.2011.02.003 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 773XA UT WOS:000291343600009 PM 21376322 ER PT J AU Thliveris, AT Clipson, L White, A Waggoner, J Plesh, L Skinner, BL Zahm, CD Sullivan, R Dove, WF Newton, MA Halberg, RB AF Thliveris, Andrew T. Clipson, Linda White, Alanna Waggoner, Jesse Plesh, Lauren Skinner, Bridget L. Zahm, Christopher D. Sullivan, Ruth Dove, William F. Newton, Michael A. Halberg, Richard B. TI Clonal Structure of Carcinogen-Induced Intestinal Tumors in Mice SO CANCER PREVENTION RESEARCH LA English DT Article ID CHIMERIC MICE; APC MUTATIONS; ORIGIN; ADENOMAS; TUMORIGENESIS; MULTIPLICITY; RESISTANCE; PLA2G2A; DNA AB Previous studies have shown that intestinal tumors from Apc(Min/+) (Min) mice and familial adenomatous polyposis (FAP) patients are often polyclonal. We sought to determine whether polyclonality is unique to tumors arising from hereditary predispositions or, instead, is a common feature of intestinal tumorigenesis in other pathways to tumorigenesis. Ethylnitrosourea-induced intestinal tumors from mice wild type at the Apc locus and chimeric for the Rosa26 lineage marker were analyzed. Many were overtly polyclonal, being composed of a mixture of Rosa26(+) and Rosa26(-) neoplastic cells. Statistical analyses revealed that polyclonality could be explained by interactions between two initiated clones separated by a very short distance. The frequency of overtly polyclonal tumors and the range of interactions estimated in this model are similar to those observed when analyzing familial tumors from Min mice. Thus, polyclonality does not depend on the familial pathway to tumorigenesis. Interactions between two initiated clones might provide a selective advantage during the early stages of intestinal tumorigenesis. Cancer Prev Res; 4(6); 916-23. (C) 2011 AACR. C1 [Thliveris, Andrew T.] Univ Wisconsin Madison, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Clipson, Linda; White, Alanna; Waggoner, Jesse; Dove, William F.] Univ Wisconsin Madison, Dept Oncol, Madison, WI USA. [Newton, Michael A.] Univ Wisconsin Madison, Dept Stat, Madison, WI USA. [Newton, Michael A.] Univ Wisconsin Madison, Dept Biostat & Med Informat, Madison, WI USA. [Plesh, Lauren; Skinner, Bridget L.; Zahm, Christopher D.; Halberg, Richard B.] Univ Wisconsin Madison, Div Gastroenterol & Hepatol, Dept Med, Madison, WI USA. [Sullivan, Ruth] Univ Wisconsin Madison, Res Anim Resource Ctr, Madison, WI USA. [Dove, William F.] Univ Wisconsin Madison, Genet Lab, Madison, WI USA. [Sullivan, Ruth; Dove, William F.; Newton, Michael A.; Halberg, Richard B.] Univ Wisconsin Madison, UW Carbone Canc Ctr, Madison, WI USA. [Thliveris, Andrew T.] William S Middleton Mem Vet Adm Med Ctr, Surg Serv, Madison, WI USA. RP Halberg, RB (reprint author), K4 532 Clin Sci Ctr, MC 5124,600 Highland Ave, Madison, WI 53792 USA. EM rbhalberg@medicine.wisc.edu OI Zahm, Christopher/0000-0002-2117-7003 FU National Cancer Institute [R01 CA123438, R37 CA63677, P30 CA014520]; UW Division of Gastroenterology and Hepatology; UW Department of Medicine; UW School of Medicine and Public Health FX The study was supported by National Cancer Institute grants R01 CA123438 (R.B. Halberg), R37 CA63677 (W.F. Dove), P30 CA014520 (UW Carbone Cancer Center Core Grant), and start-up funds to RBH from the UW Division of Gastroenterology and Hepatology, the UW Department of Medicine, and the UW School of Medicine and Public Health. NR 24 TC 6 Z9 6 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JUN PY 2011 VL 4 IS 6 BP 916 EP 923 DI 10.1158/1940-6207.CAPR-11-0022 PG 8 WC Oncology SC Oncology GA 771ZR UT WOS:000291199700017 PM 21636550 ER PT J AU Alam, M Siddiqui, S Lee, VV Elayda, MA Nambi, V Yang, EY Jneid, HM Wilson, JM Ballantyne, CM Virani, SS AF Alam, Mahboob Siddiqui, Sahar Lee, Vei-Vei Elayda, McArthur A. Nambi, Vijay Yang, Eric Y. Jneid, Hani M. Wilson, James M. Ballantyne, Christie M. Virani, Salim S. TI Isolated Coronary Artery Bypass Grafting in Obese Individuals - A Propensity Matched Analysis of Outcomes SO CIRCULATION JOURNAL LA English DT Article DE Coronary artery bypass grafting; Morbidity; Mortality; Obesity; Outcomes ID BODY-MASS INDEX; THORACIC-SURGEONS DATABASE; IN-HOSPITAL MORTALITY; LONG-TERM OUTCOMES; CARDIAC-SURGERY; EXTREME OBESITY; RISK-FACTOR; POSTOPERATIVE MORBIDITY; METABOLIC SYNDROME; HEART-FAILURE AB Background: There is conflicting data regarding the impact of obesity on morbidity and mortality in patients undergoing isolated coronary artery bypass grafting (CABG). Methods and Results: Retrospective cohort analysis of patients who underwent CABG from January 1, 1995, through July 31, 2010 was performed. Patients were classified as obese or non-obese (body mass index >= 30.0 kg/m(2) and <30.0 kg/m(2), respectively). The primary outcome was in-hospital mortality. Secondary outcomes included postoperative respiratory failure, postoperative stroke, postoperative myocardial infarction, sternal and leg wound infections, postoperative atrial fibrillation, postoperative ventricular tachycardia, postoperative renal failure and length of hospital stay. Propensity-matched stepwise multivariable logistic regression was performed. Of 13,115 patients, 4,619 (35.2%) were obese. In the propensity-matched logistic regression models (n=8,442), obesity was not associated with postoperative mortality (odds ratio=1.13, 95% confidence interval 0.86-1.48). However, obesity was associated with postoperative respiratory failure, postoperative renal insufficiency, sternal wound infection, and leg wound infection. Obesity was also associated with a decreased risk of postoperative bleeding and re-operation from bleeding. Conclusions: Obesity was associated with an increased risk of postoperative respiratory failure, postoperative renal failure, and surgical site infections. However, obesity was not associated with in-hospital mortality in patients undergoing CABG. (Circ J 2011; 75: 1378-1385) C1 [Alam, Mahboob; Nambi, Vijay; Jneid, Hani M.; Ballantyne, Christie M.; Virani, Salim S.] Baylor Coll Med, Dept Med, Cardiol Sect, Houston, TX 77030 USA. [Lee, Vei-Vei; Elayda, McArthur A.; Wilson, James M.; Virani, Salim S.] Baylor Coll Med, Texas Heart Inst, Houston, TX 77030 USA. [Nambi, Vijay; Yang, Eric Y.; Ballantyne, Christie M.; Virani, Salim S.] Baylor Coll Med, Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA. [Jneid, Hani M.; Virani, Salim S.] Baylor Coll Med, Methodist Hosp, Houston, TX 77030 USA. [Jneid, Hani M.; Virani, Salim S.] Baylor Coll Med, Hlth Policy & Qual Program, Houston, TX 77030 USA. [Siddiqui, Sahar] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA. [Siddiqui, Sahar] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Siddiqui, Sahar] Univ Florida, Sch Publ Hlth, Gainesville, FL USA. RP Alam, M (reprint author), Baylor Coll Med, Dept Med, Cardiol Sect, 1709 Dryden Rd,Suite 9-90,BCM 620, Houston, TX 77030 USA. EM malam@bcm.tmc.edu RI Yang, Eric/C-1170-2010 OI Yang, Eric/0000-0003-2234-3269; Virani, Salim/0000-0001-9541-6954 FU St. Luke's Episcopal Hospital; Department of Veterans Affairs Health Services Research and Development Service (Health Service Research Development) [CDA-09-028] FX The authors thank Ms. Joanna A. Brooks, BA, for her editorial assistance. This work was supported by the Muller Fund for Cardiovascular Research at St. Luke's Episcopal Hospital. Dr. Virani is also supported via a Department of Veterans Affairs Health Services Research and Development Service (Health Service Research & Development) Career Development Award (Grant number: CDA-09-028). NR 68 TC 11 Z9 12 U1 0 U2 2 PU JAPANESE CIRCULATION SOC PI KYOTO PA KINKI INVENTION CENTER, 14 YOSHIDA KAWAHARACHO, SAKYO-KU, KYOTO, 606-8305, JAPAN SN 1346-9843 J9 CIRC J JI Circ. J. PD JUN PY 2011 VL 75 IS 6 BP 1378 EP 1385 DI 10.1253/circj.CJ-10-1129 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 771RH UT WOS:000291177900018 PM 21498907 ER PT J AU Hall, AL Peterson, CL Kautz, SA Neptune, RR AF Hall, A. L. Peterson, C. L. Kautz, S. A. Neptune, R. R. TI Relationships between muscle contributions to walking subtasks and functional walking status in persons with post-stroke hemiparesis SO CLINICAL BIOMECHANICS LA English DT Article DE Forward dynamics simulation; Modeling; Biomechanics; Gait; Muscle function ID MECHANICAL-PROPERTIES; GAIT SPEED; STROKE; SUPPORT; PROGRESSION; WORK; CLASSIFICATION; OPTIMIZATION; FLEXORS; FORCES AB Background: Persons with post-stroke hemiparesis usually walk slowly and asymmetrically. Stroke severity and functional walking status are commonly predicted by post-stroke walking speed. The mechanisms that limit walking speed, and by extension functional walking status, need to be understood to improve post-stroke rehabilitation methods. Methods: Three-dimensional forward dynamics walking simulations of hemiparetic subjects (and speed-matched controls) with different levels of functional walking status were developed to investigate the relationships between muscle contributions to walking subtasks and functional walking status. Muscle contributions to forward propulsion, swing initiation and power generation were analyzed during the pre-swing phase of the gait cycle and compared between groups. Findings: Contributions from the paretic leg muscles (i.e., soleus, gastrocnemius and gluteus medius) to forward propulsion increased with improved functional walking status, with the non-paretic leg muscles (i.e., rectus femoris and vastii) compensating for reduced paretic leg propulsion in the limited community walker. Contributions to swing initiation from both paretic (i.e., gastrocnemius, iliacus and psoas) and non-paretic leg muscles (i.e., hamstrings) also increased as functional walking status improved. Power generation was also an important indicator of functional walking status, with reduced paretic leg power generation limiting the paretic leg contribution to forward propulsion and leg swing initiation. Interpretation: These results suggest that deficits in muscle contributions to the walking subtasks of forward propulsion, swing initiation and power generation are directly related to functional walking status and that improving output in these muscle groups may be an effective rehabilitation strategy for improving post-stroke hemiparetic walking. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Hall, A. L.; Peterson, C. L.; Neptune, R. R.] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. [Kautz, S. A.] Malcom Randall VA Med Ctr, Brain Rehabil Res Ctr, Gainesville, FL USA. [Kautz, S. A.] Med Univ S Carolina, Div Phys Therapy, Dept Hlth Sci & Res, Charleston, SC USA. [Kautz, S. A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Neptune, RR (reprint author), Univ Texas Austin, Dept Mech Engn, 1 Univ Stn C2200, Austin, TX 78712 USA. EM rneptune@mail.utexas.edu RI Kinney, Allison/J-5814-2013; Peterson, Carrie/C-6007-2016 OI Kinney, Allison/0000-0003-3553-0733; Peterson, Carrie/0000-0002-7169-2089; Kautz, Steven/0000-0003-3151-8235 FU NIH [RO1 HD46820]; Rehabilitation Research & Development Service of the VA FX The authors would like to thank Erin Carr, Dr. Mark Bowden, Dr. Bhavana Raja, Dr. Cameron Nott, Dr. Chitra Balasubramanian, Kelly Rooney and Ryan Knight for help with the data collection and processing and the members of the Neuromuscular Biomechanics Lab at The University of Texas at Austin for their insightful comments on the manuscript. This work was funded by NIH grant RO1 HD46820 and the Rehabilitation Research & Development Service of the VA. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NICHD or VA. NR 27 TC 32 Z9 32 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD JUN PY 2011 VL 26 IS 5 BP 509 EP 515 DI 10.1016/j.clinbiomech.2010.12.010 PG 7 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 771RN UT WOS:000291178500013 PM 21251738 ER PT J AU Andersson, A Srivastava, MK Harris-White, M Huang, M Zhu, L Elashoff, D Strieter, RM Dubinett, SM Sharma, S AF Andersson, Asa Srivastava, Minu K. Harris-White, Marni Huang, Min Zhu, Li Elashoff, David Strieter, Robert M. Dubinett, Steven M. Sharma, Sherven TI Role of CXCR3 Ligands in IL-7/IL-7R alpha-Fc-Mediated Antitumor Activity in Lung Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; ANGIOGENESIS IN-VIVO; X-C-CHEMOKINE; DENDRITIC CELLS; MACROPHAGE POLARIZATION; INTERFERON-GAMMA; TUMOR-ANTIGENS; INTERLEUKIN-7; IL-7; CARCINOMA AB Purpose: We evaluated the utility of chimeric gamma c homeostatic cytokine, IL-7/IL-7R alpha-Fc, to restore host APC (antigen presenting cell) and T cell activities in lung cancer. Experimental Design: Utilizing murine lung cancer models we determined the antitumor efficacy of IL-7/IL-7R alpha-Fc. APC, T cell, cytokine analyses, neutralization of CXCL9, CXCL10, and IFN gamma were carried out to evaluate the mechanistic differences in the antitumor activity of IL-7/IL-7R alpha-Fc in comparison to controls. Results: IL-7/IL-7R alpha-Fc administration inhibited tumor growth and increased survival in lung cancer. Accompanying the tumor growth inhibition were increases in APC and T cell activities. In comparison to controls, IL-7/IL-7R alpha-Fc treatment of tumor bearing mice led to increased: (i) levels of CXCL9, CXCL10, IFN gamma, IL-12 but reduced IL-10 and TGF beta, (ii) tumor macrophage infiltrates characteristic of M1 phenotype with increased IL-12, iNOS but reduced IL-10 and arginase, (iii) frequencies of T and NK cells, (iv) T cell activation markers CXCR3, CD69 and CD127(low), (v) effector memory T cells, and (vi) T cell cytolytic activity against parental tumor cells. IL-7/IL-7R alpha-Fc treatment abrogated the tumor induced reduction in splenic functional APC activity to T responder cells. The CXCR3 ligands played an important role in IL-7/IL-7R alpha-Fc-mediated antitumor activity. Neutralization of CXCL9, CXCL10, or IFN gamma reduced CXCR3 expressing activated T cells infiltrating the tumor and abrogated IL-7/IL-7R alpha-Fc-mediated tumor growth inhibition. Conclusions: Our findings show that IL-7/IL-7R alpha-Fc promotes afferent and efferent antitumor responses in lung cancer. Clin Cancer Res; 17(11); 3660-72. (C)2011 AACR. C1 [Harris-White, Marni; Huang, Min; Zhu, Li; Dubinett, Steven M.; Sharma, Sherven] Vet Affairs Greater Los Angeles Healthcare Syst, Mol Gene Med Lab, Los Angeles, CA 90073 USA. [Strieter, Robert M.] Univ Virginia, Dept Med, Charlottesville, VA USA. [Harris-White, Marni] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Huang, Min; Zhu, Li; Dubinett, Steven M.; Sharma, Sherven] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Andersson, Asa; Srivastava, Minu K.; Huang, Min; Zhu, Li; Elashoff, David; Dubinett, Steven M.; Sharma, Sherven] Univ Calif Los Angeles, UCLA Lung Canc Res Program, Dept Med, Los Angeles, CA 90095 USA. RP Sharma, S (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Mol Gene Med Lab, Los Angeles, CA 90073 USA. EM ssharma@mednet.ucla.edu FU NIH [RO1 CA95686, RO1 CA126944]; University of California Los Angeles Lung Cancer Program; Department of Veterans Affairs; University of California [18FT-0165, 15RT-0207] FX This work was supported by: NIH Grants (RO1 CA95686 and RO1 CA126944), University of California Los Angeles Lung Cancer Program, Department of Veterans Affairs Medical Research Funds, and Tobacco Related Disease Program Award Program of University of California (18FT-0165 and 15RT-0207). NR 56 TC 15 Z9 17 U1 0 U2 6 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 JUN 1 PY 2011 VL 17 IS 11 BP 3660 EP 3672 DI 10.1158/1078-0432.CCR-10-3346 PG 13 WC Oncology SC Oncology GA 772AC UT WOS:000291200800017 PM 21636553 ER PT J AU Abdelsamie, SA Li, YC Huang, Y Lee, MH Klein, RL Virella, G Lopes-Virella, MF AF Abdelsamie, Souzan A. Li, Yanchun Huang, Yan Lee, Mi-Hye Klein, Richard L. Virella, Gabriel Lopes-Virella, Maria F. TI Oxidized LDL immune complexes stimulate collagen IV production in mesangial cells via Fc gamma receptors I and III SO CLINICAL IMMUNOLOGY LA English DT Article DE Collagen; Low-density lipoprotein; Immune complexes; Nephropathy; Mesangial cells ID LOW-DENSITY-LIPOPROTEIN; DIABETIC-NEPHROPATHY; CULTURED RAT; EXTRACELLULAR-MATRIX; PATHOGENESIS; MACROPHAGES; DISEASE; PROGRESSION; EXPRESSION; ANTIBODIES AB Diabetic nephropathy is characterized by progressive mesangial expansion. Although we have reported that circulating oxidized LDL-containing immune complexes (oxLDL-IC) are associated with abnormal levels of albuminuria, the underlying mechanisms have not been investigated. In this study, we have studied the effect of oxLDL-IC on collagen IV expression by mesangial cells. We found that oxLDL-IC markedly stimulated collagen IV expression in a concentration- and time-dependent fashion while oxLDL only had moderate effect. We also found that oxLDL-IC stimulated collagen IV expression by engaging Fc gamma receptor (Fc gamma R) I and III, but not Fc gamma RII, and that p38 MAPK, JNK and PKC pathways were involved in collagen IV expression. Furthermore, we found that oxLDL-IC stimulated Fc gamma RI expression, suggesting a positive feedback mechanism involved in oxLDL-IC-stimulated collagen IV expression. Taken together, this study showed that oxLDL-IC stimulated collagen IV in mesangial cells via Fc gamma RI and Fc gamma RIII, and the expression of Fc gamma RI was increased by oxLDL-IC. Published by Elsevier Inc. C1 [Huang, Yan; Klein, Richard L.; Lopes-Virella, Maria F.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Abdelsamie, Souzan A.; Li, Yanchun; Huang, Yan; Lee, Mi-Hye; Klein, Richard L.; Lopes-Virella, Maria F.] Med Univ S Carolina, Coll Med, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Lopes-Virella, MF (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. EM virellam@musc.edu FU Department of Veterans Affairs; National Institutes of Health/NHLBI [PO1 HL 55782]; NIH/NIDDK [R01 DK081352]; Juvenile Diabetes Foundation [2006-49] FX This work was supported by a Merit Review Grant from the Department of Veterans Affairs. This work was also supported by a Program Project funded by the National Institutes of Health/NHLBI (PO1 HL 55782), by a RO1 Grant funded by NIH/NIDDK (R01 DK081352) and by a Juvenile Diabetes Foundation Grant (2006-49). NR 42 TC 15 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 2011 VL 139 IS 3 BP 258 EP 266 DI 10.1016/j.clim.2011.01.016 PG 9 WC Immunology SC Immunology GA 771QX UT WOS:000291176900006 PM 21439910 ER PT J AU Xu, YH Li, H Gao, RL Adeyemo, O Itkin, M Kaplan, DE AF Xu, Yanhui Li, Hong Gao, Rui Lin Adeyemo, Oluwasayo Itkin, Maxim Kaplan, David E. TI Expansion of interferon-gamma-producing multifunctional CD4+T-cells and dysfunctional CD8+T-cells by glypican-3 peptide library in hepatocellular carcinoma patients SO CLINICAL IMMUNOLOGY LA English DT Article DE Hepatocellular carcinoma; T-cells; Interferon-gamma; PD-1; CTLA-4 ID T-CELL RESPONSES; HEPATITIS-B-VIRUS; ALPHA-FETOPROTEIN; POSTOPERATIVE RECURRENCE; EFFECTOR FUNCTION; EX-VIVO; LIVER; EXPRESSION; CIRRHOSIS; CANCER AB Glypican-3 is a promising target for immunotherapy for hepatocellular carcinoma, but limited data exist regarding its immunogenicity in patients with diverse HLA types, immunogenicity for CD4(+) T-cells, and the impact of inhibitory co-stimulation on glypican-3-specific T-cells. Using a 15mer overlapping peptide library for glypican-3, PBMC from patients with HCC were assessed ex vivo and after short-term in vitro expansion for tumor antigen-specific T-cell responses with and without blockade of PD-1/PD-L1 and CTLA-4 signaling. Glypican-3-specific T-cells were undetectable ex vivo, but primarily IFN gamma(+)TNF alpha(+) CD4(+) T-cells expanded with short-term in vitro stimulation in 10/19 (52%) patients. Glypican-3-specific CD8(+) T-cells predominantly produced TNF alpha, but did not secrete IFN gamma nor degranulate. CTLA-4 and PD-1 blockade minimally impacted the cytokine secretion and proliferation of glypican-3-specific T-cells. These data suggest that CD8(+). T-cell-directed tumor vaccines in HCC may have limited potential for efficacy unless optimal co-stimulation conditions can be identified but CD4(+)-directed vaccines merit consideration. Published by Elsevier Inc. C1 [Kaplan, David E.] Philadelphia VA Med Ctr, Med & Res Serv, Philadelphia, PA 19104 USA. [Xu, Yanhui; Li, Hong; Gao, Rui Lin; Adeyemo, Oluwasayo; Kaplan, David E.] Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Itkin, Maxim] Univ Penn, Philadelphia VA Med Ctr, Serv Radiol, Philadelphia, PA 19104 USA. [Itkin, Maxim] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. RP Kaplan, DE (reprint author), Philadelphia VA Med Ctr, Med & Res Serv, Res Bldg 21,A402A,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM dakaplan@mail.med.upenn.edu OI Kaplan, David E./0000-0002-3839-336X FU Veterans Health Administration; University of Pennsylvania FX This work was supported by the Research Career Development Award from the Veterans Health Administration (DEK) and academic development funds from the University of Pennsylvania. The content of this article does not reflect the views of the VA or of the US Government. NR 53 TC 8 Z9 10 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 2011 VL 139 IS 3 BP 302 EP 313 DI 10.1016/j.clim.2011.02.014 PG 12 WC Immunology SC Immunology GA 771QX UT WOS:000291176900011 PM 21419713 ER PT J AU Shields, RK Kwak, EJ Potoski, BA Doi, Y Adams-Haduch, JM Silviera, FP Toyoda, Y Pilewski, JM Crespo, M Pasculle, AW Clancy, CJ Nguyen, MH AF Shields, Ryan K. Kwak, Eun J. Potoski, Brian A. Doi, Yohei Adams-Haduch, Jennifer M. Silviera, Fernando. P. Toyoda, Yoshiya Pilewski, Joseph M. Crespo, Maria Pasculle, A. William Clancy, Cornelius J. Nguyen, M. Hong TI High mortality rates among solid organ transplant recipients infected with extensively drug-resistant Acinetobacter baumannii: using in vitro antibiotic combination testing to identify the combination of a carbapenem and colistin as an effective treatment regimen SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Acinetobacter; Synergy; Colistin; Doripenem; Transplant ID POLYMYXIN-B; TIGECYCLINE; SYNERGY; PNEUMONIA AB Extensively drug-resistant (XDR) Acinetobacter baumannii infections caused 91% (10/11) mortality in transplant recipients. Isolates were colistin-susceptible initially, but susceptibility decreased during therapy in 40% (4/10). We tested antibiotic combinations against XDR Acinetobacter in vitro and demonstrated positive interactions for carbapenem colistin. Subsequently, 80% (4/5) of transplant patients were treated successfully with carbepenem-colistin regimens. Published by Elsevier Inc. C1 [Shields, Ryan K.; Kwak, Eun J.; Potoski, Brian A.; Doi, Yohei; Adams-Haduch, Jennifer M.; Silviera, Fernando. P.; Toyoda, Yoshiya; Pilewski, Joseph M.; Crespo, Maria; Pasculle, A. William; Clancy, Cornelius J.; Nguyen, M. Hong] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Clancy, CJ (reprint author), Univ Pittsburgh, Pittsburgh, PA 15213 USA. EM cjc76@pitt.edu RI Doi, Yohei/C-7110-2013 FU University of Pittsburgh School of Pharmacy; University of Pittsburgh, Department of Medicine FX The study was funded by the University of Pittsburgh School of Pharmacy and by seed support from the University of Pittsburgh, Department of Medicine to the Transplant Infectious Diseases Program (MHN and CJC). NR 26 TC 35 Z9 37 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JUN PY 2011 VL 70 IS 2 BP 246 EP 252 DI 10.1016/j.diagmicrobio.2010.12.023 PG 7 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 771CQ UT WOS:000291135200014 PM 21353436 ER PT J AU Nair, G Kim, M Nagaoka, T Olson, DE Thule, PM Pardue, MT Duong, TQ AF Nair, Govind Kim, Moon Nagaoka, Tsukasa Olson, Darin E. Thule, Peter M. Pardue, Machelle T. Duong, Timothy Q. TI Effects of common anesthetics on eye movement and electroretinogram SO DOCUMENTA OPHTHALMOLOGICA LA English DT Article DE Anesthesia; Eye movement; ERG; fMRI; Magnetic resonance imaging ID DARK-ADAPTED ELECTRORETINOGRAM; OPTICAL COHERENCE TOMOGRAPHY; PEAK VELOCITY; PHYSIOPHARMACOLOGICAL INVESTIGATIONS; RAT ELECTRORETINOGRAM; URETHANE ANESTHESIA; SCATTERING CHANGES; RETINAL RESPONSES; NITROUS-OXIDE; BLOOD-FLOW AB High-resolution magnetic resonance imaging (MRI) provides non-invasive images of retinal anatomy, physiology, and function with depth-resolved laminar resolution. Eye movement and drift, however, could limit high spatial resolution imaging, and anesthetics that minimize eye movement could significantly attenuate retinal function. The aim of this study was to determine the optimal anesthetic preparations to minimize eye movement and maximize visual-evoked retinal response in rats. Eye movements were examined by imaging of the cornea with a charge-coupled device (CCD) camera under isoflurane, urethane, ketamine/xylazine, and propofol anesthesia at typical dosages in rats. Combination of the paralytic pancuronium bromide with isoflurane or ketamine/xylazine anesthesia was also examined for the eye movement studies. Visual-evoked retinal responses were evaluated using full-field electroretinography (ERG) under isoflurane, ketamine/xylazine, urethane, and ketamine/xylazine + pancuronium anesthesia in rats. The degree of eye movement, measured as displacement per unit time, was the smallest under 1% isoflurane + pancuronium anesthesia. The ketamine/xylazine groups showed larger dark-adapted ERG a- and b-waves than other anesthetics tested. The isoflurane group showed the shortest b-wave implicit times. Photopic ERGs in the ketamine/xylazine groups showed the largest b-waves with the isoflurane group showing slightly shorter implicit times at the higher flash intensities. Oscillatory potentials revealed an early peak in the isoflurane group compared with ketamine/xylazine and urethane groups. Pancuronium did not affect the a- and b-wave, but did increase oscillatory potential amplitudes. Compared with the other anesthetics tested here, ketamine/xylazine + pancuronium was the best combination to minimize eye movement and maximize retinal function. These findings should set the stage for further development and application of high-resolution functional imaging techniques, such as MRI, to study retinal anatomy, physiology, and function in anesthetized rats. C1 [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, Dept Physiol, San Antonio, TX 78229 USA. [Nair, Govind; Nagaoka, Tsukasa] Emory Univ, Div Neurosci, Yerkes Imaging Ctr, Atlanta, GA 30322 USA. [Nair, Govind] Univ Massachusetts, Sch Med, Grad Sch Biomed Sci, Worcester, MA USA. [Nair, Govind] Worcester Polytech Inst, Worcester, MA 01609 USA. [Nair, Govind; Kim, Moon; Nagaoka, Tsukasa; Olson, Darin E.; Thule, Peter M.; Pardue, Machelle T.] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA. [Olson, Darin E.; Thule, Peter M.] Emory Univ, Div Endocrinol Metab & Lipids, Atlanta, GA 30322 USA. [Pardue, Machelle T.] Emory Univ, Dept Ophthalmol, Atlanta, GA 30322 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. [Pardue, Machelle T.] Atlanta VA Med Ctr, Rehab R&D Ctr, Decatur, GA USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, Dept Ophthalmol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM mpardue@emory.edu; duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008 FU NIH/NEI [R01 EY014211, EY018855]; Department of Veterans Affairs; Research to Prevent Blindness; NEI [P30EY006360]; Rehabilitation, Research and Development Service, Department of Veterans Affairs FX This work was supported by the NIH/NEI (R01 EY014211 and EY018855 to TQD) and MERIT awards from the Department of Veterans Affairs (TQD, MTP, DEO). We also thank Research to Prevent Blindness; NEI (P30EY006360); and Rehabilitation, Research and Development Service, Department of Veterans Affairs for their supports. NR 66 TC 18 Z9 18 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0012-4486 J9 DOC OPHTHALMOL JI Doc. Ophthalmol. PD JUN PY 2011 VL 122 IS 3 BP 163 EP 176 DI 10.1007/s10633-011-9271-4 PG 14 WC Ophthalmology SC Ophthalmology GA 774NC UT WOS:000291392300005 PM 21519880 ER PT J AU Mortensen, EM AF Mortensen, E. M. TI Potential causes of increased long-term mortality after pneumonia SO EUROPEAN RESPIRATORY JOURNAL LA English DT Editorial Material ID COMMUNITY-ACQUIRED PNEUMONIA; HOSPITALIZATION; INTERLEUKIN-6; COHORT C1 [Mortensen, E. M.] Univ Texas Hlth Ctr San Antonio, Dept Med, S Texas Vet Hlth Care Syst, VERDICT Res Program, San Antonio, TX USA. RP Mortensen, EM (reprint author), VERDICT Res Program 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM mortensene@uthscsa.edu OI Mortensen, Eric/0000-0002-3880-5563 NR 20 TC 6 Z9 6 U1 0 U2 1 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD JUN PY 2011 VL 37 IS 6 BP 1306 EP 1307 DI 10.1183/09031936.00194110 PG 2 WC Respiratory System SC Respiratory System GA 771JE UT WOS:000291152200002 PM 21632829 ER PT J AU Namjou, B Kothari, PH Kelly, JA Glenn, SB Ojwang, JO Adler, A Alarcon-Riquelme, ME Gallant, CJ Boackle, SA Criswell, LA Kimberly, RP Brown, E Edberg, J Stevens, AM Jacob, CO Tsao, BP Gilkeson, GS Kamen, DL Merrill, JT Petri, M Goldman, RR Vila, LM Anaya, JM Niewold, TB Martin, J Pons-Estel, BA Sabio, JM Callejas, JL Vyse, TJ Bae, SC Perrino, FW Freedman, BI Scofield, RH Moser, KL Gaffney, PM James, JA Langefeld, CD Kaufman, KM Harley, JB Atkinson, JP AF Namjou, B. Kothari, P. H. Kelly, J. A. Glenn, S. B. Ojwang, J. O. Adler, A. Alarcon-Riquelme, M. E. Gallant, C. J. Boackle, S. A. Criswell, L. A. Kimberly, R. P. Brown, E. Edberg, J. Stevens, A. M. Jacob, C. O. Tsao, B. P. Gilkeson, G. S. Kamen, D. L. Merrill, J. T. Petri, M. Goldman, R. R. Vila, L. M. Anaya, J-M Niewold, T. B. Martin, J. Pons-Estel, B. A. Sabio, J. M. Callejas, J. L. Vyse, T. J. Bae, S-C Perrino, F. W. Freedman, B. I. Scofield, R. H. Moser, K. L. Gaffney, P. M. James, J. A. Langefeld, C. D. Kaufman, K. M. Harley, J. B. Atkinson, J. P. CA BIOLUPUS Network GENLES Collaboration TI Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort SO GENES AND IMMUNITY LA English DT Article DE autoimmunity; SLE; TREX1 ID AICARDI-GOUTIERES-SYNDROME; GENOME-WIDE ASSOCIATION; DNA EXONUCLEASE TREX1; ERYTHEMATOSUS PATIENTS; AUTOIMMUNE-DISEASE; MUTATIONS; INTERFERONS; PROTEIN AB Systemic lupus erythematosus (SLE) is a prototypic autoimmune disorder with a complex pathogenesis in which genetic, hormonal and environmental factors have a role. Rare mutations in the TREX1 gene, the major mammalian 3'-5' exonuclease, have been reported in sporadic SLE cases. Some of these mutations have also been identified in a rare pediatric neurological condition featuring an inflammatory encephalopathy known as Aicardi-Goutieres syndrome (AGS). We sought to investigate the frequency of these mutations in a large multi-ancestral cohort of SLE cases and controls. A total of 40 single-nucleotide polymorphisms (SNPs), including both common and rare variants, across the TREX1 gene, were evaluated in similar to 8370 patients with SLE and similar to 7490 control subjects. Stringent quality control procedures were applied, and principal components and admixture proportions were calculated to identify outliers for removal from analysis. Population-based case-control association analyses were performed. P-values, false-discovery rate q values, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. The estimated frequency of TREX1 mutations in our lupus cohort was 0.5%. Five heterozygous mutations were detected at the Y305C polymorphism in European lupus cases but none were observed in European controls. Five African cases incurred heterozygous mutations at the E266G polymorphism and, again, none were observed in the African controls. A rare homozygous R114H mutation was identified in one Asian SLE patient, whereas all genotypes at this mutation in previous reports for SLE were heterozygous. Analysis of common TREX1 SNPs (minor allele frequency (MAF)>10%) revealed a relatively common risk haplotype in European SLE patients with neurological manifestations, especially seizures, with a frequency of 58% in lupus cases compared with 45% in normal controls (P = 0.0008, OR = 1.73, 95% CI = 1.25-2.39). Finally, the presence or absence of specific autoantibodies in certain populations produced significant genetic associations. For example, a strong association with anti-nRNP was observed in the European cohort at a coding synonymous variant rs56203834 (P = 2.99E-13, OR = 5.2, 95% CI = 3.18-8.56). Our data confirm and expand previous reports and provide additional support for the involvement of TREX1 in lupus pathogenesis. Genes and Immunity (2011) 12, 270-279; doi:10.1038/gene.2010.73; published online 27 January 2011 C1 [Namjou, B.; Kelly, J. A.; Glenn, S. B.; Ojwang, J. O.; Adler, A.; Alarcon-Riquelme, M. E.; Merrill, J. T.; Scofield, R. H.; Moser, K. L.; Gaffney, P. M.; James, J. A.; Kaufman, K. M.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Kothari, P. H.; Atkinson, J. P.] Washington Univ, Sch Med, St Louis, MI USA. [Alarcon-Riquelme, M. E.; Gallant, C. J.] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden. [Alarcon-Riquelme, M. E.] Univ Granada Junta de Andalucia, Ctr Genom & Oncol Res Pfizer, Granada, Spain. [Boackle, S. A.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Criswell, L. A.] Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA USA. [Kimberly, R. P.; Brown, E.; Edberg, J.] Univ Alabama, Birmingham, AL USA. [Stevens, A. M.] Univ Washington, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Jacob, C. O.] Univ So Calif, Lupus Genet Grp, Los Angeles, CA USA. [Tsao, B. P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Gilkeson, G. S.; Kamen, D. L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Petri, M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Goldman, R. R.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Anaya, J-M] Univ Rosario, Ctr Autoimmune Dis Res CREA, Bogota, Colombia. [Vila, L. M.] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. [Niewold, T. B.] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [Pons-Estel, B. A.] Sanatorio Parque, Rosario, Argentina. [Martin, J.] Inst Biomed & Parasitol Lopez Neyra, Armilla, Spain. [Sabio, J. M.] Hosp Virgen Nieves, Dept Internal Med, Granada, Spain. [Callejas, J. L.] Hosp Clin San Cecilio, Dept Internal Med, Granada, Spain. [Vyse, T. J.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. [Bae, S-C] Hanyang Univ, Hosp Rheumat Dis, Seoul 133791, South Korea. [Bae, S-C] Hanyang Univ, Dept Internal Med, Div Rheumatol, Seoul 133791, South Korea. [Perrino, F. W.; Freedman, B. I.; Langefeld, C. D.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Kaufman, K. M.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Harley, J. B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. RP Namjou, B (reprint author), Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM namjoub@omrf.org RI Vyse, Tim/G-3887-2011; Martin, Javier/B-8141-2008; Anaya, Juan-Manuel/J-1960-2016 OI Anaya, Juan-Manuel/0000-0002-6444-1249; Universidad del Rosario, Biblioteca/0000-0003-3491-9392; Kimberly, Robert/0000-0002-5330-3086; Alarcon Riquelme, Marta Eugenia/0000-0002-7632-4154; Niewold, Timothy/0000-0003-3532-6660 FU NIH [AR042460, RR015577, AR048940, RR020143, AI24717, AR62277, R21AI070304, AR044804, AR02175, AR052300, K24 AR 002138, P60 2 AR30692, PO1 AR49084, UL1RR025741, CA141700-01]; Lupus Foundation of America; Alliance for Lupus Research; US Department of Veterans Affairs; Cerebral Retinal Vasculopathy Fund; National Center for Research Resources (NCRR) [NIH AR43727, UL1RR025005, UL1RR029882]; Kirkland Scholar Award; US Public Health Service National Center for Research Resources [M01 RR-00079]; European Science Foundation; Swedish Research Council; Swedish Association against Rheumatism; Swedish International Development Agency (SIDA); Gustaf Vth-80th jubilee Foundation; [HL083822]; [NS062069]; [AR33062]; [AR49084]; [5UL1RR02777]; [R01GM069962]; [67692] FX The cooperation of patients and normal control individuals involved in this study as well as physicians that provide samples is gratefully acknowledged. At the Oklahoma Medical Research Foundation, the work was supported by the NIH (AR042460, RR015577, AR048940, RR020143, AI24717, AR62277), Lupus Foundation of America, the Alliance for Lupus Research, the US Department of Veterans Affairs. At the Washington University School of Medicine (St Louis, MO, USA), the work was supported by grants (HL083822 (PHK), and NS062069 (JPA)), and the Cerebral Retinal Vasculopathy Fund. At the University of Alabama at Birmingham, the work was supported by grants AR33062 (RPK), AR49084 (RPK) and 5UL1RR02777. At the Johns Hopkins University School of Medicine, the work was supported by The Hopkins Lupus Cohort (NIH AR43727) and UL1RR025005 from the National Center for Research Resources (NCRR). At the University of Colorado, Denver School of Medicine, the work was supported by a NIH grant R21AI070304. At the Medical University of South Carolina, Charleston, USA, the project was supported by award number UL1RR029882 from the National Center for Research Resources. (The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health). At the Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, USA, the work was supported by Kirkland Scholar Award, US Public Health Service National Center for Research Resources, M01 RR-00079 and NIH grants AR044804, AR02175 and AR052300. At the Northwestern University, Feinberg School of Medicine, Chicago, IL, USA, the work was supported by NIH grants K24 AR 002138, P60 2 AR30692, PO1 AR49084 and UL1RR025741. At the Wake Forest University Health Sciences, Department of Biochemistry, the work was supported by R01GM069962 and Alliance for Lupus Research (67692) awards. We acknowledge grants from the European Science Foundation for the BIOLUPUS network, the Swedish Research Council, Swedish Association against Rheumatism, the Swedish International Development Agency (SIDA) and Gustaf Vth-80th jubilee Foundation to MEAR and the NIH grant CA141700-01. For GENLES: Argentina: Hugo R Scherbarth, MD; Pilar C Marino, MD; Estela L Motta, MD at Servicio de Reumatologia, Hospital Interzonal General de Agudos 'Dr Oscar Alende', Mar del Plata, Argentina. Susana Gamron, MD; Cristina Drenkard, MD; Emilia Menso, MD at Servicio de Reumatologia de la UHMI 1, Hospital Nacional de Clinicas, Universidad Nacional de Cordoba, Cordoba, Argentina. Alberto Allievi, MD; Guillermo A Tate, MD at Organizacion Medica de Investigacion, Buenos Aires, Argentina. Jose L Presas, MD at Hospital General de Agudos Dr Juan A Fernandez, Buenos Aires, Argentina. Simon A Palatnik, MD; Marcelo Abdala, MD; Mariela Bearzotti, PhD at Facultad de Ciencias Medicas, Universidad Nacional de Rosario y Hospital Provincial del Centenario, Rosario, Argentina. Alejandro Alvarellos, MD; Francisco Caeiro, MD; Ana Bertoli, MD at Servicio de Reumatologia, Hospital Privado, Centro Medico de Cordoba, Cordoba, Argentina. Sergio Paira, MD; Susana Roverano, MD at Hospital Jose M. Cullen, Santa Fe, Argentina. Cesar E Graf, MD; Estela Bertero, PhD at Hospital San Martin, Parana. Cesar Caprarulo, MD; Griselda Buchanan, PhD at Hospital Felipe Heras, Concordia, Entre Rios, Argentina.; Carolina Guilleron, MD; Sebastian Grimaudo, PhD; Jorge Manni, MD at Departamento de Inmunologia, Instituto de Investigaciones Medicas 'Alfredo Lanri', Buenos Aires, Argentina. Luis J Catoggio, MD; Enrique R Soriano, MD; Carlos D Santos, MD at Seccion Reumatologia, Servicio de Clinica Medica, Hospital Italiano de Buenos Aires y Fundacion Dr Pedro M Catoggio para el Progreso de la Reumatologia, Buenos Aires, Argentina. Cristina Prigione, MD; Fernando A Ramos, MD; Sandra M Navarro, MD at Servicio de Reumatologia, Hospital Provincial de Rosario, Rosario, Argentina. Guillermo A Berbotto, MD; Marisa Jorfen, MD; Elisa J Romero, PhD at Servicio de Reumatologia Hospital Escuela Eva Peron. Granadero Baigorria, Rosario, Argentina. Mercedes A Garcia, MD; Juan C Marcos MD; Ana I Marcos, MD at Servicio de Reumatologia, Hospital Interzonal General de Agudos General San Martin, La Plata. Carlos E Perandones, MD; Alicia Eimon, MD at Centro de Educacion Medica e Investigaciones Clinicas (CEMIC), Buenos Aires, Argentina. Cristina G Battagliotti, MD at Hospital de Ninos Dr Orlando Alassia, Santa Fe, Argentina. Peru is represented by: Dr Eduardo Acevedo and Dr Mariano Cucho, Hospital Nacional Guillermo Almenara Irigoyen, Lima, Peru. Mexico is represented by Dr Ignacio Garcia de la Torre, Hospital General de Occidente, Zapopan, Jalisco; Dr Mario Cardiel Rios, Hospital General Dr Miguel Silva, Morelia, Michoacan; Dr Jose Francisco Moctezuma, Hospital General de Mexico, Mexico, DF; Dr Marco Maradiaga Cecena, Hospital General de Culiacan, Culiacan, Sinaloa. The members of the BIOLUPUS network are: Sandra D'Alfonso, Department of Medical Sciences and IRCAD, University of Eastern Piedmont, Novara, Italy; Bernard R. Lauwerys, Cliniques Universitaires Saint-Luc, Universite catholique de Louvain, Bruxells, Belgium; Emoke Endreffy, Department of Pediatrics and Health Center, University of Szeged, Szeged, Hungary; Laszlo Kovacs, Department of Rheumatology, Albert Szent-Gyorgyi Clinical Centre, University of Szeged, Szeged, Hungary; Carlos Vasconcelos, Hospital Santo Antonio and ICBAS, Porto, Portugal; Berta Martins da Silva, UMIB/ICBAS, Immunogenetics laboratory, Universidado do Porto, Porto, Portugal; Inigo Rua Figueroa, Hospital Doctor Negrin, Las Palmas de Gran Canaria, Spain. Sandra D'Alfonso, Nadia Barizzone (Department of Medical Sciences and IRCAD, University of Eastern Piedmont, Novara, Italy); Gian Domenico Sebastiani (Azienda Ospedaliera San Camillo-Forlanini, Roma, Italy); Mauro Galeazzi, (Siena University, Siena, Italy) Maria Giovanna Danieli (Clinica Medica di Scienze Mediche e Chirurgiche, Universita Politecnica delle Marche, Ancona, Italy); Giovanni La Montagna (Rheumatology Unit Second University of Naples, Naples, Italy) and Maria Grazia Sabbadini (Vita-Salute San Raffaele University of Milan, Italy). NR 35 TC 102 Z9 104 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD JUN PY 2011 VL 12 IS 4 BP 270 EP 279 DI 10.1038/gene.2010.73 PG 10 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 772BU UT WOS:000291206100004 PM 21270825 ER PT J AU Carchman, EH Rao, J Loughran, PA Rosengart, MR Zuckerbraun, BS AF Carchman, Evie H. Rao, Jayashree Loughran, Patricia A. Rosengart, Matthew R. Zuckerbraun, Brian S. TI Heme Oxygenase-1-Mediated Autophagy Protects Against Hepatocyte Cell Death and Hepatic Injury from Infection/Sepsis in Mice SO HEPATOLOGY LA English DT Article ID NF-KAPPA-B; HOST-DEFENSE; APOPTOSIS; INHIBITION; SEPSIS; SHOCK; MITOCHONDRIA; DYSFUNCTION; SURVIVAL; FAILURE AB Adaptive responses to sepsis are necessary to prevent organ failure and death. Cellular signaling responses that limit cell death and structural damage allow a cell to withstand insult from sepsis to prevent irreversible organ dysfunction. One such protective pathway to reduce hepatocellular injury is the up-regulation of heme oxygenase-1 (HO-1) signaling. HO-1 is up-regulated in the liver in response to multiple stressors, including sepsis and lipopolysaccharide (LPS), and has been shown to limit cell death. Another recently recognized rudimentary cellular response to injury is autophagy. The aim of these investigations was to test the hypothesis that HO-1 protects against hepatocyte cell death in experimental sepsis in vivo or LPS in vitro via induction of autophagy. These data demonstrate that both HO-1 and autophagy are up-regulated in the liver after cecal ligation and puncture (CLP) in C57BL/6 mice or in primary mouse hepatocytes after treatment with LPS (100 ng/mL). CLP or LPS results in minimal hepatocyte cell death. Pharmacological inhibition of HO-1 activity using tin protoporphyrin or knockdown of HO-1 prevents the induction of autophagic signaling in these models and results in increased hepatocellular injury, apoptosis, and death. Furthermore, inhibition of autophagy using 3-methyladenine or small interfering RNA specific to VPS34, a class III phosphoinositide 3-kinase that is an upstream regulator of autophagy, resulted in hepatocyte apoptosis in vivo or in vitro. LPS induced phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), in part, via HO-dependent signaling. Moreover, inhibition of p38 MAPK prevented CLP- or LPS-induced autophagy. Conclusion: Sepsis or LPS-induced autophagy protects against hepatocellular death, in part via an HO-1 p38 MAPK-dependent signaling. Further investigations are needed to elucidate how autophagic signaling prevents apoptosis and cell death. (HEPATOLOGY 2011;53:2053-2062) C1 [Carchman, Evie H.; Rao, Jayashree; Loughran, Patricia A.; Rosengart, Matthew R.; Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Sch Med, Pittsburgh, PA 15213 USA. [Carchman, Evie H.; Rao, Jayashree; Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), Univ Pittsburgh, Dept Surg, Sch Med, NW653 MUH,3459 5th Ave, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu NR 23 TC 89 Z9 96 U1 2 U2 24 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 2011 VL 53 IS 6 BP 2053 EP 2062 DI 10.1002/hep.24324 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 773KX UT WOS:000291307300029 PM 21437926 ER PT J AU Singal, AK Jampana, SC Anand, BS AF Singal, Ashwani K. Jampana, Sarat C. Anand, Bhupinderjit S. TI Comment on a Systematic Review of Randomized Trials of Peginterferon Alpha-2a Versus Peginterferon Alpha-2b in Chronic Hepatitis C SO HEPATOLOGY LA English DT Letter ID PEGYLATED INTERFERON ALPHA-2A; COINFECTED PATIENTS; PLUS RIBAVIRIN C1 [Singal, Ashwani K.] Univ Texas Med Branch, Dept Internal Med, Galveston, TX USA. [Singal, Ashwani K.; Jampana, Sarat C.] Univ Texas Med Branch, Div Gastroenterol, Galveston, TX USA. [Anand, Bhupinderjit S.] Baylor Coll Med, Dept Gastroenterol & Hepatol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Singal, AK (reprint author), Univ Texas Med Branch, Dept Internal Med, Galveston, TX USA. NR 6 TC 0 Z9 0 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 JUN PY 2011 VL 53 IS 6 BP 2151 EP 2151 DI 10.1002/hep.24165 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 773KX UT WOS:000291307300056 PM 21538429 ER PT J AU Goetz, MB Rimland, D AF Goetz, Matthew Bidwell Rimland, David TI Effect of Expanded HIV Testing Programs on the Status of Newly Diagnosed HIV-Infected Patients in Two Veterans Health Administration Facilities: 1999-2009 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter ID ANTIRETROVIRAL THERAPY; UNITED-STATES; TRANSMISSION; PREVALENCE C1 [Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Rimland, David] VA Med Ctr, Dept Med, Decatur, GA USA. [Rimland, David] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. RP Goetz, MB (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. OI Goetz, Matthew/0000-0003-4542-992X NR 12 TC 7 Z9 7 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUN 1 PY 2011 VL 57 IS 2 BP E23 EP E25 DI 10.1097/QAI.0b013e31821a0600 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 771MQ UT WOS:000291163100003 PM 21709450 ER PT J AU Tanaka, Y Nagaoka, T Nair, G Ohno, K Duong, TQ AF Tanaka, Yoji Nagaoka, Tsukasa Nair, Govind Ohno, Kikuo Duong, Timothy Q. TI Arterial spin labeling and dynamic susceptibility contrast CBF MRI in postischemic hyperperfusion, hypercapnia, and after mannitol injection SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE arterial spin labeling; arterial transit time; cerebral blood flow; dynamic susceptibility contrast; permeability; spin-lattice relaxation-time constant ID CEREBRAL-BLOOD-FLOW; CAPILLARY WATER PERMEABILITY; SINGULAR-VALUE DECOMPOSITION; HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; BRAIN-BARRIER; EMBOLIC STROKE; FUNCTIONAL MRI; TRANSIT-TIME; PERFUSION AB Arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) are widely used to image cerebral blood flow (CBF) in stroke. This study examined how changes in tissue spin-lattice relaxation-time constant (T(1)), blood-brain barrier (BBB) permeability, and transit time affect CBF quantification by ASL and DSC in postischemic hyperperfusion in the same animals. In Group I (n = 6), embolic stroke rats imaged 48 hours after stroke showed regional hyperperfusion. In normal pixels, ASL- and DSC-CBF linearly correlated pixel-by-pixel. In hyperperfusion pixels, ASL-CBF was significantly higher than DSC-CBF pixel-by-pixel (by 25%). T1 increased from 1.76 +/- 0.14 seconds in normal pixels to 1.93 +/- 0.17 seconds in hyperperfusion pixels. Arterial transit time decreased from 300 milliseconds in normal pixels to 200 milliseconds in hyperperfusion pixels. Delta R(2)* profiles showed contrast-agent leakages in the hyperperfusion regions. In Group II (n = 3) in which hypercapnic inhalation was used to increase CBF without BBB disruption, CBF increased overall but ASL- and DSC-CBF remained linearly correlated. In Group III (n = 3) in which mannitol was used to break the BBB, ASL-CBF was significantly higher than DSC-CBF. We concluded that in normal tissue, ASL and DSC provide comparable quantitative CBF, whereas in postischemic hyperperfusion, ASL-CBF and DSC-CBF differed significantly because ischemia-induced changes in T1 and BBB permeability affected the two methods differently. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 1403-1411; doi:10.1038/jcbfm.2010.228; published online 22 December 2010 C1 [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. [Tanaka, Yoji; Nagaoka, Tsukasa; Nair, Govind] Emory Univ, Yerkes Imaging Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Tanaka, Yoji; Ohno, Kikuo] Tokyo Med & Dent Univ, Dept Neurosurg, Tokyo, Japan. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008 FU NINDS NIH HHS [R01 NS045879] NR 43 TC 20 Z9 22 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2011 VL 31 IS 6 BP 1403 EP 1411 DI 10.1038/jcbfm.2010.228 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 771HY UT WOS:000291149000010 PM 21179070 ER PT J AU Bloch, MJ Basile, JN AF Bloch, Michael J. Basile, Jan N. TI Analysis of Recent Papers in Hypertension SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article C1 [Bloch, Michael J.] Univ Nevada, St Marys Reg Med Ctr, Risk Reduct Ctr, Dept Internal Med,Sch Med, Reno, NV 89503 USA. [Basile, Jan N.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Seinsheimer Cardiovasc Hlth Program, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA. RP Bloch, MJ (reprint author), Univ Nevada, St Marys Reg Med Ctr, Risk Reduct Ctr, Dept Internal Med,Sch Med, 645 N Arlington St,Suite 460, Reno, NV 89503 USA. EM mbloch@aol.com 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 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JUN PY 2011 VL 13 IS 6 BP 455 EP 457 DI 10.1111/j.1751-7176.2011.00470.x PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 774OB UT WOS:000291394800010 PM 21649846 ER PT J AU Goodman, M Siever, LJ AF Goodman, Marianne Siever, Larry J. TI Hypermentalization in Adolescents With Borderline Personality Traits: Extending the Conceptual Framework to Younger Ages SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID DISORDER C1 [Goodman, Marianne; Siever, Larry J.] Mt Sinai Sch Med, James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Goodman, M (reprint author), Mt Sinai Sch Med, James J Peters Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Marianne.Goodman@va.gov NR 11 TC 2 Z9 2 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2011 VL 50 IS 6 BP 536 EP 537 DI 10.1016/j.jaac.2011.02.013 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 773DZ UT WOS:000291288500002 PM 21621135 ER PT J AU Simpson, TL Comtois, KA Moore, SA Kaysen, D AF Simpson, Tracy L. Comtois, Katherine Anne Moore, Sally A. Kaysen, Debra TI Comparing the Diagnosis of PTSD When Assessing Worst Versus Multiple Traumatic Events in a Chronically Mentally Ill Sample SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; EFFECT SIZE; SCALE AB Despite interest in the nature of the traumatic event required to meet Criterion A for posttraumatic stress disorder (PTSD) as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994), little attention has been paid to the diagnostic ramifications of linking PTSD symptoms to a single traumatic event in the context of multiple trauma exposures. In this study, 67 dually diagnosed clients with at least 2 potential Criterion A traumatic events completed the Posttraumatic Stress Diagnostic Scale twice, in counterbalanced order: once regarding their worst event and once regarding all events. When responding regarding their worst trauma, 53.7% met probable PTSD criteria. This rose to 67.2% when considering all traumas. Although preliminary, these results suggest that linking PTSD symptoms to a single traumatic event excludes a meaningful number of cases who are otherwise indistinguishable based on symptom profile. C1 [Simpson, Tracy L.; Moore, Sally A.] VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98108 USA. [Simpson, Tracy L.; Comtois, Katherine Anne; Moore, Sally A.; Kaysen, Debra] Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Simpson, TL (reprint author), VA Puget Sound Hlth Care Syst, Mental Hlth Serv, 1660 S Columbian Way,116 WTRC, Seattle, WA 98108 USA. EM Tracy.Simpson@va.gov NR 10 TC 4 Z9 4 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2011 VL 24 IS 3 BP 361 EP 364 DI 10.1002/jts.20647 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 773ZF UT WOS:000291350300017 PM 21594901 ER PT J AU Peng, Q Zhang, Y Nateras, OSE van Osch, MJP Duong, TQ AF Peng, Qi Zhang, Yi Nateras, Oscar San Emeterio van Osch, Matthias J. P. Duong, Timothy Q. TI MRI of Blood Flow of the Human Retina SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE ASL; retinal vessels; choroids; high-resolution MRI; hypercapnia ID CARBON-DIOXIDE; FUNCTIONAL MRI; OXYGEN; INVERSION; BRAIN; RATS; DEGENERATION; HYPERCAPNIA; RELAXATION; EFFICIENCY AB This study reports a high-resolution MRI approach to image basal blood flow and hypercapnia-induced blood-flow changes in the unanesthetized human retina on a 3-T MRI scanner. Pseudo-continuous arterial spin labeling technique with static tissue suppression was implemented to minimize movement artifacts and improve blood-flow sensitivity. Turbo spin-echo acquisition was used to achieve high spatial resolution free of susceptibility artifacts. The size, shape, and position of a custom-made receive radiofrequency coil were optimized for sensitivity in the posterior retina. Synchronized eye blink and respiration to the end of each data readout minimized eye movement and physiological fluctuation. Robust high-contrast blood-flow MRI of the unanesthetized human retina was obtained at 500 X 800 mu m(2) in-plane resolution. Blood flow in the posterior retina was 93 +/- 31 mL/(100 mL min) (mean +/- standard deviation, N = 5). Hypercapnic inhalation (5% CO(2)) increased blood flow by 12 +/- 4% relative to air (P < 0.01, N = 5). This study demonstrates the feasibility of blood-flow MRI of the retina of unanesthetized human. Because blood flow is tightly coupled to metabolic function under normal conditions and it is often perturbed in diseases, this approach could provide unique insights into retinal physiology and serve as an objective imaging biomarker for disease staging and testing of novel therapeutic strategies. This approach could open up new avenue of retinal research. Magn Reson Med 65:1768-1775, 2011. (C)2011 Wiley-Liss, Inc. C1 [Peng, Qi; Zhang, Yi; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Peng, Qi; Zhang, Yi; Nateras, Oscar San Emeterio; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [van Osch, Matthias J. P.] Leiden Univ, Med Ctr, Dept Radiol, CJ Gorter Ctr High Field MRI, Leiden, Netherlands. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008 FU Clinical Translational Science Award Pilot Grant, Translational Technology Resource Grant [UL1RR025767]; NIH/NEI [R01 EY014211, EY018855]; Department of Veterans Affairs FX Grant sponsors: Clinical Translational Science Award Pilot Grant, Translational Technology Resource Grant to TQD (Parent; Grant number: UL1RR025767); Grant sponsor: NIH/NEI; Grant numbers: R01 EY014211, EY018855 to TQD; Grant sponsor: Department of Veterans Affairs (VISN7 Career Development Award and MERIT to TQD). NR 45 TC 23 Z9 23 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUN PY 2011 VL 65 IS 6 BP 1768 EP 1775 DI 10.1002/mrm.22763 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 770VB UT WOS:000291115500028 PM 21590806 ER PT J AU Vanti, C Bonfiglioli, R Calabrese, M Marinelli, F Guccione, A Violante, FS Pillastrini, P AF Vanti, Carla Bonfiglioli, Roberta Calabrese, Monica Marinelli, Francesco Guccione, Andrew Violante, Francesco Saverio Pillastrini, Paolo TI Upper limb neurodynamic test 1 and symptoms reproduction in carpal tunnel syndrome. A validity study SO MANUAL THERAPY LA English DT Article DE Neurological examination; Reproducibility of the results; Carpal tunnel syndrome ID MEDIAN NERVE; PHYSICAL-EXAMINATION; PRACTICE PARAMETER; IN-VIVO; COMPRESSION; DIAGNOSIS; CONDUCTION; TENSION; CLASSIFICATION; LOCALIZATION AB The aim of this study was to estimate the validity of the Upper Limb Neurodynamic Test 1 (ULNT1) for the diagnosis of Carpal Tunnel Syndrome (CTS) with blind comparison to a reference criterion of a compatible clinical presentation and abnormal nerve conduction. 47 subjects with suspected CTS were enrolled. All patients were tested with nerve conduction studies and ULNT1. Considering results as positive in the presence of reproduction of symptoms on affected upper limb, or side-to-side differences in elbow extension, or symptoms modified by lateral neck side-bending, we estimated sensitivity as 91.67%, specificity as 15%, positive likelihood ratio as 1.0784, negative likelihood ratio as 0.5556, and post-test probability for negative test as 40%. Using a new criterion, i.e. the reproduction of symptoms only in the first three digits of the affected hand, we estimated sensitivity as 54.17%, specificity as 70%, positive and negative likelihood ratios as 1.8056 and 0.6548, respectively, and post-test probability for positive test as 68%. Our investigation suggests that the reproduction of the typical current CTS symptoms in the affected hand during ULNT1 testing, improves estimation of the probability of the presence of this condition, even if this test alone cannot be used to diagnose CTS. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Bonfiglioli, Roberta; Calabrese, Monica; Marinelli, Francesco; Violante, Francesco Saverio; Pillastrini, Paolo] Alma Mater Studiorum Univ Bologna, Dept Internal Med Geriatr & Nephrol, Sect Occupat Med, I-40138 Bologna, Italy. [Vanti, Carla] Univ Bologna, Sch Physiotherapy, I-40055 Bologna, Italy. [Guccione, Andrew] US Dept Vet Affairs, Hlth Serv Res & Dev Serv, Off Res & Dev, Washington, DC 20420 USA. RP Pillastrini, P (reprint author), Alma Mater Studiorum Univ Bologna, Dept Internal Med Geriatr & Nephrol, Sect Occupat Med, Via P Palagi 9, I-40138 Bologna, Italy. EM cavanti@tin.it; roberta.bonfiglioli@unibo.it; monica.calabrese5@unibo.it; francesco.marinelli5@unibo.it; andrewguccione@cox.net; francesco.violante@unibo.it; paolo.pillastrini@unibo.it RI Pillastrini, Paolo/R-4901-2016 OI VANTI, CARLA/0000-0002-7741-9200 NR 55 TC 9 Z9 9 U1 0 U2 8 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1356-689X J9 MANUAL THER JI Man. Ther. PD JUN PY 2011 VL 16 IS 3 BP 258 EP 263 DI 10.1016/j.math.2010.11.003 PG 6 WC Rehabilitation SC Rehabilitation GA 772AH UT WOS:000291201300008 PM 21185222 ER PT J AU Subramanian, S Shahaf, G Ozeri, E Miller, LM Vandenbark, AA Lewis, EC Offner, H AF Subramanian, Sandhya Shahaf, Galit Ozeri, Eyal Miller, Lisa M. Vandenbark, Arthur A. Lewis, Eli C. Offner, Halina TI Sustained expression of circulating human alpha-1 antitrypsin reduces inflammation, increases CD4+FoxP3+Treg cell population and prevents signs of experimental autoimmune encephalomyelitis in mice SO METABOLIC BRAIN DISEASE LA English DT Article DE hAAT; EAE; Tregs; Pro-inflammatory cytokines; CCR6 ID REGULATORY T-CELLS; OBSTRUCTIVE PULMONARY-DISEASE; ALPHA(1)-ANTITRYPSIN DEFICIENCY; RHEUMATOID-ARTHRITIS; AUGMENTATION THERAPY; MULTIPLE-SCLEROSIS; ULCERATIVE-COLITIS; DIABETES-MELLITUS; IMPAIRED ACTIVITY; TH17 RESPONSES AB Alpha-1-antitrypsin (AAT) is the primary circulating serine protease inhibitor, and is known to exert potent anti-inflammatory effects and to inhibit the progression of several autoimmune diseases. In this study, transgenic mice that over-express surfactant-driven human (h)AAT on the C57BL/6 background were evaluated for resistance to MOG-35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE), compared to WT C57BL/6 control mice. According to the results, sustained levels of circulating hAAT profoundly inhibited induction of clinical signs, inflammatory lesions and demyelination observed in WT mice with EAE, concomitant with enhanced levels of CD4+FoxP3+ Treg cells, reduced secretion of MOG peptide-induced pro-inflammatory cytokines, IL-17, IL-1 beta & IL-6, diminished expression of caspase-1 and enhanced expression of CCR6. These results implicate hAAT as a potent immunoregulatory agent worthy of further investigation as a potential therapy in human autoimmune diseases including multiple sclerosis. C1 [Subramanian, Sandhya; Miller, Lisa M.; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Neuroimmunol Res RD 31, Portland, OR 97239 USA. [Shahaf, Galit; Ozeri, Eyal; Lewis, Eli C.] Ben Gurion Univ Negev, Fac Hlth Sci, Beer Sheva, Israel. [Miller, Lisa M.; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. RP Offner, H (reprint author), Portland VA Med Ctr, Neuroimmunol Res RD 31, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu RI LEWIS, ELI/F-1552-2012 FU Biomedical Laboratory R&D Service, Department of Veterans' Affairs; Israel Science Foundation [1027/07] FX This work was supported by the Biomedical Laboratory R&D Service, Department of Veterans' Affairs and the Israel Science Foundation 1027/07. NR 52 TC 22 Z9 25 U1 0 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD JUN PY 2011 VL 26 IS 2 BP 107 EP 113 DI 10.1007/s11011-011-9239-9 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 774OT UT WOS:000291396700002 PM 21437674 ER PT J AU Dziennis, S Mader, S Akiyoshi, K Ren, XF Ayala, P Burrows, GG Vandenbark, AA Herson, PS Hurn, PD Offner, HA AF Dziennis, Suzan Mader, Sarah Akiyoshi, Kozaburo Ren, Xuefang Ayala, Patricia Burrows, Gregory G. Vandenbark, Arthur A. Herson, Paco S. Hurn, Patricia D. Offner, Halina A. TI Therapy with recombinant T-cell receptor ligand reduces infarct size and infiltrating inflammatory cells in brain after middle cerebral artery occlusion in mice SO METABOLIC BRAIN DISEASE LA English DT Article DE Cerebral ischemia; T-cells; Inflammation; Neuroprotection; Therapeutic ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ISCHEMIC-STROKE; RAT-BRAIN; MULTIPLE-SCLEROSIS; MESSENGER-RNA; ACTIVATION; CD44; LYMPHOCYTES; MECHANISMS; EXPRESSION AB Stroke induces a biphasic effect on the peripheral immune response that involves early activation of peripheral leukocytes followed by severe immunosuppression and atrophy of the spleen. Peripheral immune cells, including T lymphocytes, migrate to the brain and exacerbate the developing infarct. Recombinant T-cell receptor (TCR) Ligand (RTL)551 is designed as a partial TCR agonist for myelin oligodendrocyte glycoprotein (MOG)-reactive T cells and has demonstrated the capacity to limit infarct volume and inflammation in brain when administered to mice undergoing middle cerebral artery occlusion (MCAO). The goal of this study was to determine if RTL551 could retain protection when given within the therapeutically relevant 4 h time window currently in clinical practice for stroke patients. RTL551 was administered subcutaneously 4 h after MCAO, with repeated doses every 24 h until the time of euthanasia. Cell numbers were assessed in the brain, blood, spleen and lymph nodes and infarct size was measured after 24 and 96 h reperfusion. RTL551 reduced infarct size in both cortex and striatum at 24 h and in cortex at 96 h after MCAO and inhibited the accumulation of inflammatory cells in brain at both time points. At 24 h post-MCAO, RTL551 reduced the frequency of the activation marker, CD44, on T-cells in blood and in the ischemic hemisphere. Moreover, RTL551 reduced expression of the chemokine receptors, CCR5 in lymph nodes and spleen, and CCR7 in the blood and lymph nodes. These data demonstrate effective treatment of experimental stroke with RTL551 within a therapeutically relevant 4 h time window through immune regulation of myelin-reactive inflammatory T-cells. C1 [Offner, Halina A.] Portland VA Med Ctr, Neuroimmunol Res R&D 31, Portland, OR 97239 USA. [Vandenbark, Arthur A.; Offner, Halina A.] Vet Affairs Med Ctr, Portland, OR 97239 USA. [Dziennis, Suzan; Mader, Sarah; Akiyoshi, Kozaburo; Ren, Xuefang; Ayala, Patricia; Herson, Paco S.; Hurn, Patricia D.; Offner, Halina A.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. [Burrows, Gregory G.; Vandenbark, Arthur A.; Offner, Halina A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Burrows, Gregory G.] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA. RP Offner, HA (reprint author), Portland VA Med Ctr, Neuroimmunol Res R&D 31, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NIH [NR003521, NS047661]; Collins Medical Trust; AHA [09POST2190040]; Biomedical Laboratory R&D Service, Department of Veterans' Affairs FX The authors wish to thank Dr. Sushmita Sinha and Ms. Sandhya Subramanian for helpful discussions and Ms. Eva Niehaus for assistance in preparing the manuscript. This work was supported by NIH Grant NR003521 (PDH), NIH Grant NS047661 (AAV), the Collins Medical Trust (SD), AHA grant 09POST2190040 (SD), and the Biomedical Laboratory R&D Service, Department of Veterans' Affairs. NR 40 TC 19 Z9 19 U1 0 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD JUN PY 2011 VL 26 IS 2 BP 123 EP 133 DI 10.1007/s11011-011-9241-2 PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 774OT UT WOS:000291396700004 PM 21472429 ER PT J AU Byers, AL Yaffe, K AF Byers, Amy L. Yaffe, Kristine TI Depression and risk of developing dementia SO NATURE REVIEWS NEUROLOGY LA English DT Review ID MILD COGNITIVE IMPAIRMENT; LATE-LIFE DEPRESSION; WHITE-MATTER HYPERINTENSITIES; ALZHEIMERS-DISEASE; HIPPOCAMPAL VOLUME; MAJOR DEPRESSION; GERIATRIC DEPRESSION; NEUROTROPHIC FACTOR; CEREBROVASCULAR-DISEASE; VASCULAR DEPRESSION AB Depression is highly common throughout the life course and dementia is common in late life. Depression has been linked with dementia, and growing evidence implies that the timing of depression may be important in defining the nature of this association. In particular, earlier-life depression (or depressive symptoms) has consistently been associated with a more than twofold increase in dementia risk. By contrast, studies of late-life depression and dementia risk have been conflicting; most support an association, yet the nature of this association (for example, if depression is a prodrome or consequence of, or risk factor for dementia) remains unclear. The likely biological mechanisms linking depression to dementia include vascular disease, alterations in glucocorticoid steroid levels and hippocampal atrophy, increased deposition of amyloid-beta plaques, inflammatory changes, and deficits of nerve growth factors. Treatment strategies for depression could interfere with these pathways and alter the risk of dementia. Given the projected increase in dementia incidence in the coming decades, understanding whether treatment for depression alone, or combined with other regimens, improves cognition is of critical importance. In this Review, we summarize and analyze current evidence linking late-life and earlier-life depression and dementia, and discuss the primary underlying mechanisms and implications for treatment. C1 [Byers, Amy L.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Byers, Amy L.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Byers, AL (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St,116H, San Francisco, CA 94121 USA. EM amy.byers@ucsf.edu FU National Institute of Mental Health [K01 MH079093, R01 MH086498]; National Institute on Aging [K24 AG031155] FX This work was supported by the National Institute of Mental Health (grant K01 MH079093 to A. L. Byers and R01 MH086498 to K. Yaffe) and the National Institute on Aging (grant K24 AG031155 to K. Yaffe). NR 128 TC 171 Z9 180 U1 4 U2 46 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD JUN PY 2011 VL 7 IS 6 BP 323 EP 331 DI 10.1038/nrneurol.2011.60 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 774LM UT WOS:000291387500008 PM 21537355 ER PT J AU Kosten, TA AF Kosten, Therese A. TI Pharmacologically targeting the P2rx4 gene on maintenance and reinstatement of alcohol self-administration in rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Ivermectin; Purinergic system; P2X(4) receptors; Relapse; Operant conditioning ID P2X(4) RECEPTOR CHANNELS; ETHANOL-SEEKING BEHAVIOR; DRUG-ADDICTION; ION CHANNELS; IVERMECTIN; RELAPSE; NEURONS; NEUROBIOLOGY; POTENTIATION; CONSUMPTION AB Genetic studies indicate that alcohol consumption associates with expression of the P2rx4 gene, a gene that codes for the P2X(4) receptor. This receptor is a subtype in the purinergic system of ligand-gated ion channels that when activated exerts excitatory effects in CNS. P2X(4) function is inhibited by alcohol and P2X(4) receptors are modulated positively by the antiparasitic agent, ivermectin. Two experiments were performed to test the ability of ivermectin to alter the behavioral effects of alcohol in rats. After alcohol exposure was achieved via the "drinking in the dark" procedure, separate groups of Sprague-Dawley rats were trained to lever press for either alcohol (10% ethanol/2% sucrose) or sucrose (3%) solutions in operant chambers. Rats were tested for maintenance of operant self-administration under a progressive ratio condition (Experiment 1) and for reinstatement of extinguished responding induced by solution presentation (Experiment 2) after ivermectin (0; 1-10 mg/kg; IP) administration. Ivermectin decreased the amount of work that the animal performed to obtain reinforcers in the maintenance study, particularly in the group reinforced with alcohol, and tended to decrease reinstated lever press responding. Conditioned approach behavior (head entries) was significantly reduced by ivermectin in both experiments. Reduction in motor activity was seen during the longer maintenance sessions but not in the shorter reinstatement sessions. Results suggest some support for ivermectin-like drugs as potential treatment agents for alcohol dependence. Caution is warranted due to modest specificity on behavior reinforced by alcohol, some reduction in general activity levels, and the lack of dose-response effects. (C) 2011 Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Dept Psychiat & Behav Sci, Michael E Debakey Vet Adm Med Ctr, Houston, TX 77030 USA. RP Kosten, TA (reprint author), Baylor Coll Med, Dept Psychiat & Behav Sci, Michael E Debakey Vet Adm Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM tkosten@bcm.edu FU [U01-AA013476] FX This research was supported by grant U01-AA013476. We greatly acknowledge the technical assistance provided by A. Aruffo, W. Huang, M. Kosten, P. O'Malley, M. Rengasamy, J. Taylor, W. Webb, and X. Xiang. NR 51 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUN PY 2011 VL 98 IS 4 BP 533 EP 538 DI 10.1016/j.pbb.2011.02.026 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 773GP UT WOS:000291295300006 PM 21402096 ER PT J AU Kruger, EA Im, DD Bischoff, DS Pereira, CT Huang, WB Rudkin, GH Yamaguchi, DT Miller, TA AF Kruger, Erwin A. Im, Daniel D. Bischoff, David S. Pereira, Clifford T. Huang, Weibiao Rudkin, George H. Yamaguchi, Dean T. Miller, Timothy A. TI In Vitro Mineralization of Human Mesenchymal Stem Cells on Three-Dimensional Type I Collagen versus PLGA Scaffolds: A Comparative Analysis SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CYCLIC TENSILE STRAIN; OSTEOGENIC DIFFERENTIATION; CHEMOKINE RECEPTORS; EXPRESSION; PROLIFERATION; HYPOXIA; STIMULATION; MATRICES; MIGRATE; CULTURE AB Background: Development of a tissue engineered bone graft requires efficient bioactivity screening of biomaterials in clinically relevant three-dimensional systems. The authors analyzed the relative osteogenic potential of two three-dimensional biomaterials-type I collagen and poly(L-lactide-co-glycolide) (PLGA)-to support in vitro mineralization of human mesenchymal stem cells. Methods: Human mesenchymal stem cells were seeded onto three-dimensional PLGA or type I collagen scaffolds; incubated in osteogenic media; and harvested at 1, 4, and 7 days. Messenger RNA expression was analyzed using quantitative real-time reverse-transcriptase polymerase chain reaction for osteogenic (i.e., alkaline phosphatase, osteocalcin, bone sialoprotein, Runx2/core binding factor alpha-1) and angiogenic (i.e., vascular endothelial growth factor and interleukin-8) markers. Alkaline phosphatase enzyme activity was measured at 4 and 7 days. Mineralization was detected by alizarin red staining and micro-computed tomographic imaging at 8 and 12 weeks. Mineral composition was analyzed by solid-phase nuclear magnetic resonance spectroscopy. Results: Early osteogenic and angiogenic markers, and alkaline phosphatase enzyme activity, were up-regulated on PLGA versus collagen scaffolds. However, long-term mineralization endpoints favored type I collagen. By 8 weeks, human mesenchymal stem cells on collagen exhibited significantly higher mineral density by micro-computed tomographic and alizarin red staining than PLGA scaffolds. Both biomaterials deposited calcium hydroxyapatite as determined by nuclear magnetic resonance spectroscopy. Conclusions: The authors' findings suggest that despite early PLGA induction of osteogenic gene expression, long-term mineralization occurs earlier and to a greater extent on type I collagen, highlighting collagen as a potential bone tissue engineering scaffold in the human mesenchymal stem cell niche. When screening the relative osteoinductive profiles of three-dimensional bone tissue engineering scaffolds in vitro, the authors recommend including long-term endpoints of osteogenesis. (Plast. Reconstr. Surg. 127: 2301, 2011.) C1 [Miller, Timothy A.] Vet Affairs Greater Los Angeles Healthcare Syst, Plast Surg Lab, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Plast & Reconstruct Surg, Dept Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Albert Einstein Coll Med, Bronx, NY USA. Harbor UCLA Med Ctr, Dept Surg, Torrance, CA USA. RP Miller, TA (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Plast Surg Lab, Room 221,Bldg 114,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM tmiller@mednet.ucla.edu FU Veterans Affairs National Merit Review Grant FX This work was supported by a Veterans Affairs National Merit Review Grant awarded to Dr. Timothy Miller. The authors thank Nalini Makhijani of the Veterans Affairs Research Service for assistance in cell culture and Dr. Robert Taylor of the University of California, Los Angeles Department of Chemistry for assistance with nuclear magnetic resonance spectroscopy. NR 35 TC 14 Z9 14 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 2011 VL 127 IS 6 BP 2301 EP 2311 DI 10.1097/PRS.0b013e318213a004 PG 11 WC Surgery SC Surgery GA 772DP UT WOS:000291212700047 PM 21617464 ER PT J AU Singh, JA Sarkin, A Shieh, M Khanna, D Terkeltaub, R Lee, SJ Kavanaugh, A Hirsch, JD AF Singh, Jasvinder A. Sarkin, A. Shieh, M. Khanna, D. Terkeltaub, R. Lee, S. J. Kavanaugh, A. Hirsch, J. D. TI Health Care Utilization in Patients with Gout SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE health care utilization; gout; predictors; resource utilization; gout severity ID QUALITY-OF-LIFE; MEDICAL-RECORD; MYOCARDIAL-INFARCTION; SELF-REPORTS; SERUM URATE; ARTHRITIS; VALIDITY; COSTS; POPULATION; DISEASE AB Objective: To study health care utilization patterns in patients with gout. Methods: In a gout population from primary care and rheumatology clinics in 3 U.S. metropolitan cities, we collected data on gout-related utilization (primary care, rheumatology, urgent care, emergency room, and other) in the past year. We evaluated the association of comorbidities, age, gender, gout characteristics (time since last gout attack and tophi), and gout severity ratings (mean of serum uric acid, patient-rated, and physician-rated gout severity) and with emergency/urgent care and primary care utilization using regression and correlation analyses. Results: Of the 296 patients who reported visiting at least 1 type of health practitioner for gout in the past year, the percentage of patients utilizing the service at least once and annual utilization rates among utilizers were as follows: primary care physician, 60%, 3.0 +/- 3.4; nurse practitioner/physician assistant, 26%, 2.7 +/- 2.5; rheumatologist, 51%, 3.7 +/- 5.7; urgent care, 23%, 2.1 +/- 2.2; emergency room, 20%, 2.0 +/- 1.7; and hospitalization, 7%, 2.1 +/- 1.4. Higher overall gout severity was associated with greater use of each resource type and with overall gout-related utilization. Nonemergency/nonurgent care utilization (primary care physician, nurse practitioner, physician's assistant, and rheumatologist for gout) was the strongest predictor of gout-related emergency/urgent care utilization. Patients with more comorbidities had greater gout-related primary care utilization. Conclusions: Overall gout severity was associated with all types of gout-related utilization. This may help to screen high utilizers for targeted behavioral and therapeutic interventions. Having a higher number of comorbid conditions was a risk factor for higher gout-related primary care utilization. Published by Elsevier Inc. Semin Arthritis Rheum 40:501-511 C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama, Birmingham, AL USA. [Sarkin, A.; Shieh, M.] Univ Calif San Diego, Hlth Serv Res Ctr, San Diego, CA 92103 USA. [Khanna, D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Terkeltaub, R.; Lee, S. J.; Kavanaugh, A.; Hirsch, J. D.] VA San Diego Healthcare Syst, San Diego, CA USA. [Hirsch, J. D.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Takeda Pharmaceutical Products, Inc; San Diego General Clinical Research Center [M01 RR00827]; National Center for Research Resources, National Institutes of Health; National Institutes of Health [NIAMS K23 AR053858-01A1, 1 KL2 RR024151-01]; VA Research Service; University of California; Department of Veterans Affairs; Arthritis Foundation; University of Minnesota; Cochrane centers; Minnesota Medical Foundation; Allergan; Takeda; Savient; Wyeth; Amgen; URL Pharmaceuticals; Novartis; TAP; Takeda pharmaceuticals; Regeneron; Research Service of the Department of Veterans Affairs FX This work was supported by the Takeda Pharmaceutical Products, Inc, VA Research Service and the University of California, San Diego General Clinical Research Center Program, M01 RR00827, National Center for Research Resources, National Institutes of Health. D.K. was also supported by a National Institutes of Health Award (NIAMS K23 AR053858-01A1) during this period. J.A.S. was supported by a National Institutes of Health CTSA Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research). R.T. was supported by the VA Research Service.; Disclosure Statement: J.A.S. has received speaker honoraria from Abbott, research grants from Department of Veterans Affairs, National Institutes of Health, Arthritis Foundation, University of Minnesota, Cochrane centers, Minnesota Medical Foundation, research and travel grants from Allergan, Takeda, Savient, Wyeth, and Amgen and consultant fees from Savient, URL Pharmaceuticals, and Novartis. J.D.H. has received a research grant from TAP and Takeda pharmaceuticals and consultant fees from Regeneron. R.T. is a consultant for Takeda, Savient, EnzymeRx, Altus, BioCryst, Regeneron, Novartis, Pfizer, URL Pharma, and Proctor & Gamble and has received grants from the Research Service of the Department of Veterans Affairs and Takeda Pharmaceuticals. D.K. has received consultant fees and research grants from Takeda Pharmaceuticals. A.K. has received consultant fees from URL pharmaceuticals. All other authors have no conflicts of interest to disclose. NR 29 TC 21 Z9 21 U1 3 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD JUN PY 2011 VL 40 IS 6 BP 501 EP 511 DI 10.1016/j.semarthrit.2010.07.001 PG 11 WC Rheumatology SC Rheumatology GA 772ZZ UT WOS:000291278100002 PM 20828793 ER PT J AU Siegel, JM AF Siegel, Jerome M. TI REM sleep: A biological and psychological paradox SO SLEEP MEDICINE REVIEWS LA English DT Editorial Material ID EYE-MOVEMENT SLEEP; IN-VIVO MICRODIALYSIS; LOCUS-COERULEUS; MEDIAL MEDULLA; BLOOD-PRESSURE; GABA RELEASE; CATAPLEXY; NEURONS; NARCOLEPSY; PONTINE C1 [Siegel, Jerome M.] Vet Adm Greater Los Angeles Healthcare Syst, Neurobiol Res 151A3, North Hills, CA 91343 USA. [Siegel, Jerome M.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Siegel, Jerome M.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. RP Siegel, JM (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Neurobiol Res 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM JSiegel@ucla.edu FU BLRD VA [I01 BX001753]; NIDA NIH HHS [R01 DA034748]; NIMH NIH HHS [R01 MH064109, R01 MH064109-09]; NINDS NIH HHS [R01 NS014610, R01 NS014610-30, R01 NS069640, R01 NS069640-01] NR 58 TC 25 Z9 25 U1 3 U2 26 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1087-0792 J9 SLEEP MED REV JI Sleep Med. Rev. PD JUN PY 2011 VL 15 IS 3 BP 139 EP 142 DI 10.1016/j.smrv.2011.01.001 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 771QE UT WOS:000291175000001 PM 21482156 ER PT J AU Campbell, J Prochazka, A Gopal, R AF Campbell, Jessica Prochazka, Allan Gopal, Ravi TI The Need for a Uniform Use of the Construct of Burnout Reply SO ACADEMIC MEDICINE LA English DT Letter ID PERCEIVED MEDICAL ERRORS; ASSOCIATION; DISTRESS C1 [Campbell, Jessica; Prochazka, Allan; Gopal, Ravi] Univ Colorado, Denver Sch Med, Aurora, CO USA. [Campbell, Jessica] Denver Hlth Med Ctr, Div Hosp Med, Denver, CO USA. [Prochazka, Allan; Gopal, Ravi] Denver VA Med Ctr, Dept Ambulatory Care, Denver, CO USA. RP Campbell, J (reprint author), Univ Colorado, Denver Sch Med, Aurora, CO USA. EM jessica.campbell@dhha.org NR 7 TC 0 Z9 0 U1 2 U2 4 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 JUN PY 2011 VL 86 IS 6 BP 661 EP 661 DI 10.1097/ACM.0b013e318218858f PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 769IM UT WOS:000291006100003 ER PT J AU Scott, DR Weimer, M English, C Shaker, L Ward, W Choi, D Cedfeldt, A Girard, D AF Scott, David R. Weimer, Melissa English, Clea Shaker, Lynn Ward, William Choi, Dongseok Cedfeldt, Andrea Girard, Donald TI A Novel Approach to Increase Residents' Involvement in Reporting Adverse Events SO ACADEMIC MEDICINE LA English DT Article ID IMPROVE PATIENT SAFETY; QUALITY IMPROVEMENT; MEDICAL ERRORS; TEACHING HOSPITALS; PHYSICIANS; EDUCATION AB Purpose In the wake of the Patient Safety and Quality Improvement Act of 2005, national attention has increasingly focused on adverse-event reporting as a means of identifying systems changes to improve patient safety. However, physicians and residents have demonstrated meager involvement in this effort. Method In 2008-2009, the authors measured participation in adverse-event reporting by 680 residents at Oregon Health & Science University before and after implementing a quality improvement initiative, which consisted of a financial incentive and multifaceted educational campaign. The primary measure of success was an increase in the average monthly adverse-event reports submitted by residents to greater than 5% of the institution's overall report submissions. Results The average number of adverse events reported by residents increased from 1.6% to 9.0% of the institution's overall event reports, representing a 5.6-fold increase during the initiative (P < .001). The relative percentage of resident-submitted reports defined as "near-misses" increased from 6% to 27% during the initiative (P < .001). Conclusions The novel approach of integrating a retirement benefit and educational campaign to increase residents' involvement in adverse-event reporting was successful. In addition to increasing residents' contributions to adverse-event reporting to levels higher than any documented in the current literature, there was also a remarkable increase in the relative frequency of near-miss reporting by residents. C1 [Scott, David R.; Weimer, Melissa] Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med & Geriatr, Portland, OR 97239 USA. [Scott, David R.] Portland VA Med Ctr, Dept Med, Portland, OR USA. [Ward, William] Mayo Clin, Dept Primary Care Internal Med, Rochester, MN USA. [Choi, Dongseok] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Girard, Donald] Oregon Hlth & Sci Univ, Dept Grad & Continuing Med Educ, Portland, OR 97239 USA. RP Scott, DR (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med & Geriatr, 3181 SW Sam Jackson Pk Rd,OP-30, Portland, OR 97239 USA. EM scottdav@ohsu.edu RI Ward, William/C-7052-2013 FU Oregon Health & Science University FX Salary support was obtained from Oregon Health & Science University. NR 16 TC 11 Z9 11 U1 9 U2 15 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 JUN PY 2011 VL 86 IS 6 BP 742 EP 746 DI 10.1097/ACM.0b013e318217e12a PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 769IM UT WOS:000291006100026 PM 21512369 ER PT J AU Wang, XR Zhang, MW Chen, DD Zhang, Y Chen, AF AF Wang, Xiao-Rong Zhang, Ming-Wei Chen, Dan-Dan Zhang, Yun Chen, Alex F. TI AMP-activated protein kinase rescues the angiogenic functions of endothelial progenitor cells via manganese superoxide dismutase induction in type 1 diabetes SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE protein phosphatase 2A; angiogenesis; oxidase stress ID SUPPRESSING OXIDATIVE STRESS; NITRIC-OXIDE SYNTHASE; VASCULAR COMPLICATIONS; SKELETAL-MUSCLE; UP-REGULATION; HYPERTENSION; EXPRESSION; MICE; DIFFERENTIATION; VASCULOPATHY AB Endothelial progenitor cells (EPCs) play an essential role in angiogenesis but are functionally impaired in diabetes. We recently reported that decreased expression of manganese superoxide dismutase (MnSOD) critically contributes to diabetic EPC dysfunction. AMP-activated protein kinase (AMPK) activation has been shown to induce MnSOD and suppress hyperglycemia-induced mitochondrial ROS production in endothelial cells. However, whether AMPK protects EPCs from oxidative stress in diabetes is unknown. We tested the hypothesis that AMPK activation rescues impaired EPC functions through MnSOD induction in type 1 diabetes. Bone marrow-derived EPCs from adult male streptozotocin-induced diabetic mice and normal controls were used. AMPK activity was decreased in diabetic EPCs, indicated by reduced AMPK and acetyl-CoA carboxylase phosphorylation. AMPK activation by treating diabetic EPCs with its selective agonist AICAR rescued their in vitro functions, including Matrigel tube formation, adhesion, and migration. Furthermore, AICAR restored the decreased MnSOD protein and enzymatic activity and suppressed the mitochondrial superoxide level in diabetic EPCs, indicated by MitoSOX flow cytometry. These beneficial effects of AICAR on MnSOD and EPC functions were significantly attenuated by silencing MnSOD or AMPK antagonist compound C pretreatment. Finally, the expression of protein phosphatase 2A, a key enzyme for AMPK dephosphorylation and inactivation, was increased in diabetic EPCs, and its inhibition by siRNA or okadaic acid reversed the deficient AMPK activation and MnSOD level in diabetic EPCs. These findings demonstrate for the first time that AMPK activation rescues impaired EPC functions and suppresses mitochondrial superoxide by inducing MnSOD in type 1 diabetes. C1 [Chen, Alex F.] Univ Pittsburgh, Sch Med, Dept Surg, Vasc Med Inst,McGowan Inst Regenerat Med, Pittsburgh, PA 15213 USA. [Wang, Xiao-Rong; Zhang, Ming-Wei; Zhang, Yun] Shandong Univ, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Minist Educ, Dept Cardiol,Qilu Hosp, Jinan 250100, Peoples R China. [Wang, Xiao-Rong; Zhang, Ming-Wei; Zhang, Yun] Shandong Univ, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Minist Publ Hlth, Dept Cardiol,Qilu Hosp, Jinan 250100, Peoples R China. [Wang, Xiao-Rong; Zhang, Ming-Wei; Chen, Dan-Dan; Chen, Alex F.] Vet Affairs Pittsburgh Healthcare Syst, Vasc Surg Res, Pittsburgh, PA USA. RP Chen, AF (reprint author), Univ Pittsburgh, Sch Med, Dept Surg, Vasc Med Inst,McGowan Inst Regenerat Med, W1148 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15213 USA. EM chena5@upmc.edu FU National Institute of General Medical Science [R01 GM-077352]; American Diabetes Association [7-08-RA-23]; American Heart Association [09POST2370060] FX This work was funded by Grant R01 GM-077352 from the National Institute of General Medical Science; Grant 7-08-RA-23 from the American Diabetes Association (to A. F. Chen). X. R. Wang is the recipient of an American Heart Association postdoctoral fellowship award (09POST2370060). NR 42 TC 32 Z9 34 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 2011 VL 300 IS 6 BP E1135 EP E1145 DI 10.1152/ajpendo.00001.2011 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 768SP UT WOS:000290959000021 PM 21427411 ER PT J AU Chen, YL Brand, A Morrison, EL Silao, FGS Bigol, UG Malbas, FF Nett, JE Andes, DR Solis, NV Filler, SG Averette, A Heitman, J AF Chen, Ying-Lien Brand, Alexandra Morrison, Emma L. Silao, Fitz Gerald S. Bigol, Ursela G. Malbas, Fedelino F., Jr. Nett, Jeniel E. Andes, David R. Solis, Norma V. Filler, Scott G. Averette, Anna Heitman, Joseph TI Calcineurin Controls Drug Tolerance, Hyphal Growth, and Virulence in Candida dubliniensis SO EUKARYOTIC CELL LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CRYPTOCOCCUS-NEOFORMANS; ASPERGILLUS-FUMIGATUS; OROPHARYNGEAL CANDIDIASIS; ANTIFUNGAL SUSCEPTIBILITY; TRANSCRIPTION FACTOR; DENTURE STOMATITIS; INFECTED PATIENTS; CALCOFLUOR WHITE; GENE-EXPRESSION AB Candida dubliniensis is an emerging pathogenic yeast species closely related to Candida albicans and frequently found colonizing or infecting the oral cavities of HIV/AIDS patients. Drug resistance during C. dubliniensis infection is common and constitutes a significant therapeutic challenge. The calcineurin inhibitor FK506 exhibits synergistic fungicidal activity with azoles or echinocandins in the fungal pathogens C. albicans, Cryptococcus neoformans, and Aspergillus fumigatus. In this study, we show that calcineurin is required for cell wall integrity and wild-type tolerance of C. dubliniensis to azoles and echinocandins; hence, these drugs are candidates for combination therapy with calcineurin inhibitors. In contrast to C. albicans, in which the roles of calcineurin and Crz1 in hyphal growth are unclear, here we show that calcineurin and Crz1 play a clearly demonstrable role in hyphal growth in response to nutrient limitation in C. dubliniensis. We further demonstrate that thigmotropism is controlled by Crz1, but not calcineurin, in C. dubliniensis. Similar to C. albicans, C. dubliniensis calcineurin enhances survival in serum. C. dubliniensis calcineurin and crz1/crz1 mutants exhibit attenuated virulence in a murine systemic infection model, likely attributable to defects in cell wall integrity, hyphal growth, and serum survival. Furthermore, we show that C. dubliniensis calcineurin mutants are unable to establish murine ocular infection or form biofilms in a rat denture model. That calcineurin is required for drug tolerance and virulence makes fungus-specific calcineurin inhibitors attractive candidates for combination therapy with azoles or echinocandins against emerging C. dubliniensis infections. C1 [Chen, Ying-Lien; Averette, Anna; Heitman, Joseph] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. [Brand, Alexandra; Morrison, Emma L.] Univ Aberdeen, Inst Med Sci, Sch Med Sci, Aberdeen Fungal Grp, Aberdeen, Scotland. [Silao, Fitz Gerald S.] Dr Jose G Tamayo Med Univ, Univ Perpetual Help, Dept Microbiol & Parasitol, Binan, Laguna, Philippines. [Bigol, Ursela G.] Dept Sci & Technol, Environm & Biotechnol Div, Bicutan, Philippines. [Malbas, Fedelino F., Jr.] Res Inst Trop Med, Alabang, Philippines. [Nett, Jeniel E.; Andes, David R.] Univ Wisconsin, Dept Med, Madison, WI USA. [Nett, Jeniel E.; Andes, David R.] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. [Nett, Jeniel E.; Andes, David R.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Solis, Norma V.; Filler, Scott G.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Filler, Scott G.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Heitman, J (reprint author), Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. EM heitm001@duke.edu OI Brand, Alexandra/0000-0002-7381-131X; Chen, Ying-Lien/0000-0002-1966-470X FU Duke University Center for AIDS Research (CFAR) [2P30 AI064518-06]; NIH [P30 AI64518, R01DE017088]; NIH/NIAID [AI42159, AI50438] FX This research was supported by the Duke University Center for AIDS Research (CFAR grant 2P30 AI064518-06 to Y.-L. Chen), NIH-funded program P30 AI64518 to Duke University, and NIH/NIAID R01 grants AI42159 and AI50438 (to J. Heitman). S. G. Filler and N. V. Solis were supported in part by NIH grant R01DE017088. NR 91 TC 41 Z9 43 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD JUN PY 2011 VL 10 IS 6 BP 803 EP 819 DI 10.1128/EC.00310-10 PG 17 WC Microbiology; Mycology SC Microbiology; Mycology GA 770MP UT WOS:000291091100011 PM 21531874 ER PT J AU Biagtan, MJ Viswanathan, RK Evans, MD Mathur, SK AF Biagtan, Mark J. Viswanathan, Ravi K. Evans, Michael D. Mathur, Sameer K. TI Clinical utility of the Chronic Urticaria Index SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID CHRONIC IDIOPATHIC URTICARIA; CHRONIC AUTOIMMUNE URTICARIA C1 [Biagtan, Mark J.; Viswanathan, Ravi K.; Mathur, Sameer K.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Viswanathan, Ravi K.; Mathur, Sameer K.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Evans, Michael D.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. RP Biagtan, MJ (reprint author), Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA. EM sm4@medicine.wisc.edu OI Evans, Michael/0000-0001-7449-3993 FU NIAID NIH HHS [AI007635, T32 AI007635-12, T32 AI007635] NR 10 TC 9 Z9 9 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2011 VL 127 IS 6 BP 1626 EP 1627 DI 10.1016/j.jaci.2011.01.045 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 769WH UT WOS:000291048500047 PM 21376378 ER PT J AU Molitch, ME Clemmons, DR Malozowski, S Merriam, GR Vance, ML AF Molitch, Mark E. Clemmons, David R. Malozowski, Saul Merriam, George R. Vance, Mary Lee TI Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GH-REPLACEMENT THERAPY; BONE-MINERAL DENSITY; QUALITY-OF-LIFE; INTIMA-MEDIA THICKNESS; TRAUMATIC BRAIN-INJURY; CARDIOVASCULAR RISK-FACTORS; BASE-LINE CHARACTERISTICS; RECOMBINANT HUMAN GH; BODY-MASS INDEX; BENIGN INTRACRANIAL HYPERTENSION AB Objective: The aim was to update The Endocrine Society Clinical Practice Guideline on Evaluation and Treatment of Adult Growth Hormone Deficiency (GHD) previously published in 2006. Consensus Process: Consensus was guided by systematic reviews of evidence and discussions through a series of conference calls and e-mails. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocrine Society. A second draft was reviewed and approved by The Endocrine Society Council. At each stage of review, the Task Force received written comments and incorporated substantive changes. Conclusions: GHD can persist from childhood or be newly acquired. Confirmation through stimulation testing is usually required unless there is a proven genetic/structural lesion persistent from childhood. GH therapy offers benefits in body composition, exercise capacity, skeletal integrity, and quality of life measures and is most likely to benefit those patients who have more severe GHD. The risks associated with GH treatment are low. GH dosing regimens should be individualized. The final decision to treat adults with GHD requires thoughtful clinical judgment with a careful evaluation of the benefits and risks specific to the individual. (J Clin Endocrinol Metab 96: 1587-1609, 2011) C1 [Molitch, Mark E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Clemmons, David R.] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. [Malozowski, Saul] Natl Inst Diabet Digest & Kidney Dis, NIH, Bethesda, MD 20892 USA. [Merriam, George R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98493 USA. [Merriam, George R.] Univ Washington, Sch Med, Tacoma, WA USA. [Vance, Mary Lee] Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22908 USA. RP Molitch, ME (reprint author), Endocrine Soc, 8401 Connecticut Ave,Suite 900, Chevy Chase, MD 20815 USA. EM govt-prof@endo-society.org FU Eli Lilly, Co.; American Diabetes Association; American College of Physicians; Pituitary Society; Sanofi Aventis; Ipsen; Corcept; Pfizer, Inc.; Genentech, Inc.; Lilly Inc.; Ipsen Inc.; America Neuroendocrine Society; National Institutes of Health; Washington State Health Department; Novo Nordisk, Inc.; Novartis Pharmaceuticals FX Financial Disclosures of the Task Force: Mark E. Molitch, M. D. (chair)-Financial or Business/Organizational Interests: Eli Lilly, Co., American Diabetes Association, American College of Physicians, Pituitary Society, Sanofi Aventis, Ipsen, Corcept; Significant Financial Interest or Leadership Position: none declared. David R. Clemmons, M. D.-Financial or Business/Organizational Interests: Pfizer, Inc., Genentech, Inc., Lilly Inc., Ipsen Inc.; Significant Financial Interest or Leadership Position: none declared. Saul Malozowski, M. D.-Financial or Business/Organizational Interests: none declared; Significant Financial Interest or Leadership Position: none declared. George R. Merriam, M. D.-Financial or Business/Organizational Interests: America Neuroendocrine Society, National Institutes of Health, Washington State Health Department; Significant Financial Interest or Leadership Position: Novo Nordisk, Inc., Eli Lilly, Co., American Neuroendocrine Society. Mary Lee Vance, M. D.-Financial or Business/Organizational Interests: Novartis Pharmaceuticals, Ipsen; Significant Financial Interest or Leadership Position: none declared. NR 215 TC 198 Z9 211 U1 1 U2 14 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2011 VL 96 IS 6 BP 1587 EP 1609 DI 10.1210/jc.2011-0179 PG 23 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 766TU UT WOS:000290810200029 PM 21602453 ER PT J AU Jessup, JA Zhang, LL Chen, AF Presley, TD Kim-Shapiro, DB Chappell, MC Wang, H Groban, L AF Jessup, Jewell A. Zhang, Lili Chen, Alex F. Presley, Tennille D. Kim-Shapiro, Daniel B. Chappell, Mark C. Wang, Hao Groban, Leanne TI Neuronal nitric oxide synthase inhibition improves diastolic function and reduces oxidative stress in ovariectomized mRen2.Lewis rats SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Diastolic function; Fibrosis; Left ventricular modeling; Myocardial relaxation; Nitric oxide; Postmenopausal ID LEFT-VENTRICULAR HYPERTROPHY; HEART-FAILURE; POSTMENOPAUSAL WOMEN; VASCULAR TETRAHYDROBIOPTERIN; PRESSURE-OVERLOAD; SYSTOLIC FUNCTION; RECEPTOR BLOCKER; BLOOD-PRESSURE; ADVANCED-STAGE; ESTROGEN AB Objective: The loss of estrogen in mRen2.Lewis rats leads to an exacerbation of diastolic dysfunction. Because specific neuronal nitric oxide synthase (nNOS) inhibition reverses renal damage in the same model, we assessed the effects of inhibiting neuronal nitric oxide on diastolic function, left ventricular remodeling, and the components of the cardiac nitric oxide system in ovariectomized (OVX) and sham-operated mRen2.Lewis rats treated with N(5)-(1-imino-3-butenyl)-L-ornithine (L-VNIO; 0.5 mg/kg per day for 28 d) or vehicle (saline). Methods: Female mRen2.Lewis rats underwent either bilateral oophorectomy (OVX; n = 15) or sham operation (or surgical procedure) (sham; n = 19) at 4 weeks of age. Beginning at 11 weeks of age, the rats were randomized to receive either L-VNIO or vehicle. Results: The surgical loss of ovarian hormones, particularly estrogen, led to exacerbated hypertension, impaired myocardial relaxation, diminished diastolic compliance, increased perivascular fibrosis, and increased relative wall thickness. The cardiac tetrahydrobiopterin-to-dihydrobiopterin levels were lower among OVX rats compared with sham-operated rats, and this altered cardiac biopterin profile was associated with enhanced myocardial superoxide production and decreased nitric oxide release. L-VNIO decreased myocardial reactive oxygen species production, increased nitrite concentrations, attenuated cardiac remodeling, and improved diastolic function. Conclusions: Impaired relaxation, diastolic stiffness, and cardiac remodeling were found among OVX mRen2.Lewis rats. A possible mechanism for this unfavorable cardiac phenotype may have resulted from a deficiency in available tetrahydrobiopterin and subsequent increase in nNOS-derived superoxide and reduction in nitric oxide synthase metabolites within the heart. Selective nNOS inhibition with L-VNIO attenuated cardiac superoxide production and limited remodeling, leading to improved diastolic function in OVX mRen2.Lewis rats. C1 [Wang, Hao; Groban, Leanne] Wake Forest Univ, Dept Anesthesiol, Sch Med, Winston Salem, NC 27157 USA. [Jessup, Jewell A.; Groban, Leanne] Wake Forest Univ, Dept Physiol & Pharmacol, Sch Med, Winston Salem, NC 27157 USA. [Zhang, Lili; Chen, Alex F.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Chen, Alex F.] Vet Affairs Pittsburgh Healthcare Syst, Vasc Surg Res, Pittsburgh, PA USA. [Presley, Tennille D.; Kim-Shapiro, Daniel B.] Winston Salem State Univ, Dept Chem, Winston Salem, NC USA. [Kim-Shapiro, Daniel B.] Wake Forest Univ, Translat Sci Ctr, Winston Salem, NC 27157 USA. [Chappell, Mark C.] Wake Forest Univ, Hypertens & Vasc Res Ctr, Sch Med, Winston Salem, NC 27157 USA. RP Groban, L (reprint author), Wake Forest Univ, Dept Anesthesiol, Sch Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM lgroban@wfubmc.edu FU National Institutes of Health [R01-AG033727-01, K08-AG026764-05, HL058091, R01 GM077352, HL-56973]; American Heart Association [0855601GH] FX The work described here was supported in part by grants from the National Institutes of Health R01-AG033727-01 (L.G.), K08-AG026764-05 Paul Beeson Award (L.G.), National Institutes of Health HL058091 (D.B.K.-S.), R01 GM077352 (A.F.C.), HL-56973 (M.C.C.), and American Heart Association Grant-in-Aid 0855601GH (A.F.C.). NR 53 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUN PY 2011 VL 18 IS 6 BP 698 EP 708 DI 10.1097/gme.0b013e31820390a2 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 769HV UT WOS:000291004400018 PM 21293310 ER PT J AU Dosa, E Tuladhar, S Muldoon, LL Hamilton, BE Rooney, WD Neuwelt, EA AF Dosa, Edit Tuladhar, Suchita Muldoon, Leslie L. Hamilton, Bronwyn E. Rooney, William D. Neuwelt, Edward A. TI MRI Using Ferumoxytol Improves the Visualization of Central Nervous System Vascular Malformations SO STROKE LA English DT Article DE central nervous system; ferumoxytol; magnetic resonance imaging; ultrasmall superparamagnetic iron oxide nanoparticles; vascular malformations ID IRON-OXIDE; CONTRAST AGENT; PARTICLES; VENOGRAPHY; MECHANISMS; BRAIN AB Background and Purpose-Central nervous system vascular malformations (VMs) result from abnormal vasculo-and/or angiogenesis. Cavernomas and arteriovenous malformations are also sites of active inflammation. The aim of this study was to determine whether MRI detection of VMs can be improved by administration of ferumoxytol iron oxide nanoparticle, which acts as a blood pool agent at early time points and an inflammatory marker when taken up by tissue macrophages. Methods-Nineteen patients (11 men, 8 women; mean age, 47.5 years) with central nervous system VMs underwent 3-T MRI both with gadoteridol and ferumoxytol. The ferumoxytol-induced signal changes on the T1-, T2-, and susceptibility-weighted images were analyzed at 25 minutes (range, 21 to 30 minutes) and 24 hours (range, 22 to 27 hours). Results-Thirty-five lesions (capillary telangiectasia, n = 6; cavernoma, n = 21; developmental venous anomaly, n = 7; arteriovenous malformation, n = 1) were seen on the pre- and postgadoteridol images. The postferumoxytol susceptibility-weighted sequences revealed 5 additional VMs (3 capillary telangiectasias, 2 cavernomas) and demonstrated further tributary veins in all patients with developmental venous anomalies. The 24-hour T1 and T2 ferumoxytol-related signal abnormalities were inconsistent among patients and within VM types. No additional area of T1 or T2 enhancement was noted with ferumoxytol compared with gadoteridol in any lesion. Conclusions-Our findings indicate that the blood pool agent ferumoxytol provides important information about the number and true extent of VMs on the susceptibility-weighted MRI. The use of ferumoxytol as a macrophage imaging agent in the visualization of inflammatory cells within and around the lesions warrants further investigation. (Stroke. 2011;42:1581-1588.) C1 [Dosa, Edit; Tuladhar, Suchita; Muldoon, Leslie L.; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Hamilton, Bronwyn E.] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97239 USA. [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97239 USA. [Rooney, William D.] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97239 USA. [Neuwelt, Edward A.] Portland VA Med Ctr, Portland, OR USA. RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,L603, Portland, OR 97239 USA. EM neuwelte@ohsu.edu FU National Institutes of Health, National Cancer Institute [CA137488]; National Institute of Neurological Disorders and Stroke [NS53468]; American Recovery and Reinvestment Ac [CA137488-15S1]; National Cancer Institute-Fredrick Cancer Research and Development Center; AMAG FX This work was supported by National Institutes of Health grants National Cancer Institute CA137488, National Institute of Neurological Disorders and Stroke NS53468, American Recovery and Reinvestment Act CA137488-15S1, and an National Cancer Institute-Fredrick Cancer Research and Development Center Contract to E.A.N.; AMAG Pharmaceuticals, Inc provided the study drug ferumoxytol free of charge. Oregon Health and Science University has received a sponsored research agreement from AMAG to conduct clinical trials of MRI with ferumoxytol. None of the authors has financial interest in this agent or in its developer, AMAG. NR 20 TC 27 Z9 28 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 JUN PY 2011 VL 42 IS 6 BP 1581 EP 1588 DI 10.1161/STROKEAHA.110.607994 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 769QH UT WOS:000291032700034 PM 21493906 ER PT J AU Krieger, JN Dobrindt, U Riley, DE Oswald, E AF Krieger, John N. Dobrindt, Ulrich Riley, Donald E. Oswald, Eric TI Acute Escherichia coli Prostatitis in Previously Health Young Men: Bacterial Virulence Factors, Antimicrobial Resistance, and Clinical Outcomes SO UROLOGY LA English DT Article ID URINARY-TRACT-INFECTION; MOLECULAR EPIDEMIOLOGY; PHYLOGENETIC GROUP; STRAINS; PYELONEPHRITIS; COMMENSALISM; GENOTYPES; ADHESINS; CYSTITIS; ISLAND AB OBJECTIVES To investigate clinical outomes, bacterial virulence factors, and antimicrobial resistance in E. coli from young men presenting with acute bacterial prostatitis. METHODS Initial E. coli isolates from previously healthy young men with no factors compromising urinary tract anatomy or function were tested for virulence-associated genes by polymerase chain reaction (PCR) assays, phylogenetic grouping by triplex polymerase PCR, and antibiotic resistance. RESULTS All 18 patients responded to treatment, including 2 who required long-term therapy. E. coli were allocated to phylogenetic groups B2 (13 strains) and D (5 strains). Prostatitis isolates belonged to clones mainly represented by extraintestinal pathogenic E. coli (ExPEC) and preferentially uropathogenic E. coli and displayed marked accumulation of virulence genes (hly, cdt1, clb, pap, sfa/foc, fyuA, iroN, kpsMT(II), and traT) characteristic of highly virulent ExPEC. All phylogenetic group B2 strains coded for at least 1 toxin with carcinogenic potential (Colibactin, cytolethal distending toxins, or cytotoxic necrotizing factor). In contrast to their accumulation of virulence-associated traits, prostatitis strains were sensitive to standard antibiotics. CONCLUSIONS The phylogenetic background and accumulation of an exceptional repertoire of extraintestinal pathogenic virulence-associated genes indicate that these E. coli strains belong to a highly virulent subset of uropathogenic variants. In contrast, antibiotic resistance was minimal in these E. coli strains from previously healthy, young outpatients. UROLOGY 77: 1420-1425, 2011. Published by Elsevier Inc. C1 [Krieger, John N.] Univ Washington, Sch Med, Dept Urol Surg, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Munster, Inst Hyg, Munster, Germany. CHU Toulouse, Lab Bacteriol Hyg, Toulouse, France. Univ Toulouse, Fac Med Purpan, Toulouse, France. RP Krieger, JN (reprint author), Univ Washington, Sch Med, Dept Urol Surg, VA Puget Sound Hlth Care Syst, UW Campus Mail Box 358280, Seattle, WA 98108 USA. EM jkrieger@uw.edu FU ERA-NET project; German Research Foundation [DO 789/4-1] FX This study was supported in part by the ERA-NET project, "Deciphering the intersection of extraintestinal pathogenic and commensal Escherichia coli." The authors would like to thank Michele Boury (Toulouse) and Barbara Plaschke (Wurzburg) for their excellent technical support. D was supported by the German Research Foundation (DO 789/4-1). NR 30 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JUN PY 2011 VL 77 IS 6 BP 1420 EP 1425 DI 10.1016/j.urology.2010.12.059 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 769VX UT WOS:000291047500049 PM 21459419 ER PT J AU Durazzo, TC Tosun, D Buckley, S Gazdzinski, S Mon, A Fryer, SL Meyerhoff, DJ AF Durazzo, Timothy C. Tosun, Duygu Buckley, Shannon Gazdzinski, Stefan Mon, Anderson Fryer, Susanna L. Meyerhoff, Dieter J. TI Cortical Thickness, Surface Area, and Volume of the Brain Reward System in Alcohol Dependence: Relationships to Relapse and Extended Abstinence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Dependence; Neuroimaging; Brain Volume; Cortical Thickness; Surface Area; Relapse ID MAGNETIC-RESONANCE SPECTROSCOPY; CONSUMPTION FOLLOWING TREATMENT; NATIONAL EPIDEMIOLOGIC SURVEY; SUBSTANCE USE DISORDERS; HUMAN CEREBRAL-CORTEX; ADDICTED HUMAN BRAIN; DSM-IV ALCOHOL; ORBITOFRONTAL CORTEX; UNITED-STATES; DRUG-USE AB Background: At least 60% of those treated for an alcohol use disorder will relapse. Empirical study of the integrity of the brain reward system (BRS) is critical to understanding the mechanisms of relapse as this collection of circuits is implicated in the development and maintenance of all forms of addictive disorders. This study compared thickness, surface area, and volume in neocortical components of the BRS among nonsmoking light-drinking controls (controls), individuals who remained abstinent and those who relapsed after treatment. Methods: Seventy-five treatment-seeking alcohol-dependent individuals (abstinent for 7 +/- 3 days) and 43 controls completed 1.5T proton magnetic resonance imaging studies. Parcellated morphological data were obtained for following bilateral components of the BRS: rostral and caudal anterior cingulate cortex, insula, medial and lateral orbitofrontal cortex (OFC), rostral and caudal middle and superior frontal gyri, amygdala and hippocampus as well as for 26 other bilateral neocortical regions. Alcohol-dependent participants were followed over 12-months after baseline study and were classified as abstainers (no alcohol consumption; n = 24) and relapsers (any alcohol consumption; n = 51) at follow-up. Results: Relapsers and abstainers demonstrated lower cortical thickness in the vast majority of BRS regions as well as lower global thickness compared to controls. Relapsers had lower total BRS surface area than both controls and abstainers, but abstainers were not significantly different from controls on any surface area measure. Relapsers demonstrated lower volumes than controls in the majority of regions, while abstainers showed lower volumes than controls in the superior frontal gyrus, insula, amygdala, and hippocampus, bilaterally. Relapsers exhibited smaller volumes than abstainers in the right rostral middle and caudal middle frontal gyri and the lateral OFC, bilaterally. In relapsers, lower baseline volumes and surface areas in multiple regions were associated with a greater magnitude of post-treatment alcohol consumption. Conclusions: Results suggest relapsers demonstrated morphological abnormalities in regions involved in the "top down" regulation/modulation of internal drive states, emotions, reward processing, and behavior, which may impart increased risk for the relapse/remit cycle that afflicts many with an alcohol use disorder. Results also highlight the importance of examining both cortical thickness and surface area to better understand the nature of regional volume loss frequently observed in alcohol use disorders. Results from this report are consistent with previous research implicating plastic neurobiological changes in the BRS in the maintenance of addictive disorders. C1 [Durazzo, Timothy C.; Mon, Anderson; Fryer, Susanna L.; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Durazzo, Timothy C.; Tosun, Duygu; Buckley, Shannon; Gazdzinski, Stefan; Mon, Anderson; Fryer, Susanna L.; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. RP Durazzo, TC (reprint author), San Francisco Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St,114M, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu FU National Institutes of Health [AA10788, DA24136] FX This material is the result of work supported by National Institutes of Health (AA10788 to D.J.M. and DA24136 to T.C.D.) and with resources and the use of facilities at the San Francisco Veterans Administration Medical Center, San Francisco CA. We thank Mary Rebecca Young, Bill Clift, Jeanne Eichenbaum and Drs. Peter Banys and Ellen Herbst of the Veterans Administration Substance Abuse Day Hospital and Dr. David Pating, Karen Moise and their colleagues at the Kaiser Permanente Chemical Dependency Recovery Program in San Francisco for their valuable assistance in recruiting participants. We also extend our gratitude to the study participants, who made this research possible. NR 93 TC 79 Z9 79 U1 2 U2 15 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 JUN PY 2011 VL 35 IS 6 BP 1187 EP 1200 DI 10.1111/j.1530-0277.2011.01452.x PG 14 WC Substance Abuse SC Substance Abuse GA 765FG UT WOS:000290688200021 PM 21410483 ER PT J AU Tschanz, JT Corcoran, CD Schwartz, S Treiber, K Green, RC Norton, MC Mielke, MM Piercy, K Steinberg, M Rabins, PV Leoutsakos, JM Welsh-Bohmer, KA Breitner, JCS Lyketsos, CG AF Tschanz, JoAnn T. Corcoran, Chris D. Schwartz, Sarah Treiber, Katherine Green, Robert C. Norton, Maria C. Mielke, Michelle M. Piercy, Kathleen Steinberg, Martin Rabins, Peter V. Leoutsakos, Jeanne-Marie Welsh-Bohmer, Kathleen A. Breitner, John C. S. Lyketsos, Constantine G. TI Progression of Cognitive, Functional, and Neuropsychiatric Symptom Domains in a Population Cohort With Alzheimer Dementia: The Cache County Dementia Progression Study SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Alzheimer disease; Alzheimer dementia; cognition; decline; dementia; neuropsychiatric symptoms; progression ID MINI-MENTAL-STATE; VASCULAR FACTORS; DISEASE; DECLINE; PROGNOSIS; AD; PREDICTORS; EPSILON-4; EDUCATION; SEVERITY AB Objectives: Progression of Alzheimer dementia (AD) is highly variable. Most estimates derive from convenience samples from dementia clinics or research centers where there is substantial potential for survival bias and other distortions. In a population-based sample of incident AD cases, we examined progression of impairment in cognition, function, and neuropsychiatric symptoms, and the influence of selected variables on these domains. Design: Longitudinal, prospective cohort study. Setting: Cache County (Utah). Participants: Three hundred twenty-eight persons with a diagnosis of possible/probable AD. Measurements: Mini-Mental State Exam (MMSE), Clinical Dementia Rating sum-of-boxes (CDR-sb), and Neuropsychiatric Inventory (NPI). Results: Over a mean follow-up of 3.80 (range: 0.07-12.90) years, the mean (SD) annual rates of change were -1.53 (2.69) scale points on the MMSE, 1.44 (1.82) on the CDR-sb, and 2.55 (5.37) on the NPI. Among surviving participants, 30% to 58% progressed less than 1 point per year on these measures, even 5 to 7 years after dementia onset. Rates of change were correlated between MMSE and CDR-sb (r = -0.62, df = 201, p < 0.001) and between the CDR-sb and NPI (r = 0.20, df = 206, p < 0.004). Female subjects (LR chi(2) = 8.7, df = 2, p = 0.013) and those with younger onset (likelihood ratio [LR] chi(2) = 5.7, df = 2, p = 0.058) declined faster on the MMSE. Although one or more apolipoprotein E epsilon 4 alleles and ever use of FDA-approved antidementia medications were associated with initial MMSE scores, neither was related to the rate of progression in any domain. Conclusions: A significant proportion of persons with AD progresses slowly. The results underscore differences between population-based versus clinic-based samples and suggest ongoing need to identify factors that may slow the progression of AD. (Am J Geriatr Psychiatry 2011; 19:532-542) C1 [Tschanz, JoAnn T.; Corcoran, Chris D.; Schwartz, Sarah; Norton, Maria C.; Piercy, Kathleen] Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. [Tschanz, JoAnn T.; Treiber, Katherine; Norton, Maria C.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Corcoran, Chris D.] Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. [Norton, Maria C.; Piercy, Kathleen] Utah State Univ, Dept Family Consumer & Human Dev, Logan, UT 84322 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Med Genet, Boston, MA 02215 USA. [Mielke, Michelle M.; Steinberg, Martin; Rabins, Peter V.; Leoutsakos, Jeanne-Marie; Lyketsos, Constantine G.] Johns Hopkins Univ, Dept Psychiat, Johns Hopkins Bayview & Sch Med, Baltimore, MD USA. [Welsh-Bohmer, Kathleen A.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Welsh-Bohmer, Kathleen A.] Duke Univ, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC USA. [Breitner, John C. S.] Univ Washington, Sch Med, Seattle, WA USA. [Breitner, John C. S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Tschanz, JT (reprint author), Utah State Univ, Ctr Epidemiol Studies, 4440 Old Main Hill, Logan, UT 84322 USA. EM joann.tschanz@usu.edu RI Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013; Schwartz, Sarah/E-2050-2016 OI Schwartz, Sarah/0000-0001-9980-7493; Steinberg, Martin/0000-0001-8800-8020 FU NIH [R01AG-21136, R01AG11380, R01AG18712, R01HG02213, P30AG028377, K24AG027841, P30AG13846, NIA AG11380, NIA AG028377]; DPS; NIMH; NIA; Associated Jewish Federation of Baltimore; Weinberg Foundation; Forest; Glaxo-Smith-Kline; Eisai; Pfizer; Astra-Zeneca; Lilly; Ortho-McNeil; Bristol-Myers; Novartis FX This study is supported by NIH grants: R01AG-21136, R01AG11380, R01AG18712, R01HG02213, P30AG028377, K24AG027841, and P30AG13846.; The authors thank Dr Ronald Munger for his unqualified support of the DPS. They also thank the following individuals whose activities have helped to ensure the success of the project: Cara Brewer, B. A., Tony Calvert, B. A., R.N., Michelle Carlson, Ph.D., Elizabeth Fauth, Ph.D., Kimberly Graham, B. A., Kyle Hess, M. S., Hochang Ben Lee, M. D., Carol Leslie, M. S., Lawrence S. Mayer, Ph.D., Chiadi U. Onyike, M. D., Roxane Pfister, M. S., Georgiann Sanborn, M. S., Nancy Sassano, Ph.D., Ingmar Skoog, M. D., Heidi Wengreen, Ph. D., RD, James Wyatt, and Peter P. Zandi, Ph. D., M. P. H. Finally, they thank the participants and their families for their participation and support.; Authors disclosure: Peter V. Rabins: Legal testimony for Janssen Pharmaceutical; Martin Steinberg: Grant support from NIA and Elan Pharmaceuticals; Kathleen A. Welsh-Bohmer: 1) Scientific advisory board for Medivation, Inc. 2) Received funding for travel and speaker honoraria from Medivation, Inc., and Elan Corporation/Wyeth. 3) Has served/serves as an associate editor of Neuropsychology Review, on the editorial boards of Alzheimer's & Dementia, the Journal International Neuropsychological Society, and the Journal of Experimental and Clinical Neuropsychology, and as a consulting editor for Aging, Neuropsychology, and Cognition and Neuropsychology. 4) Holds US Patent #6867236 (issued 2005): Nonsteroidal Anti-inflammatory drugs for the treatment of Alzheimer's disease. 5) Receives royalties from the publication of Geriatric Neuropsychology: Assessment and Intervention (Guildford Publications, 2006). 6) Receives research support from the NIH (NIA AG11380 [PI] and NIA AG028377 [PI]); Constantine Lyketsos: 1) Grant support (research or CME)-NIMH, NIA, Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest, Glaxo-Smith-Kline, Eisai, Pfizer, Astra-Zeneca, Lilly, Ortho-McNeil, Bristol-Myers, Novartis. 2) Consultant/Advisor-Astra-Zeneca, Glaxo-Smith Kline, Eisai, Novartis, Forest, Supernus, Adlyfe, Takeda, Wyeth, Lundbeck, Merz, Lilly, Genentech. 3) Honorarium or travel support-Pfizer, Forest, Glaxo-Smith Kline, Health Monitor; JoAnn Tschanz, Chris Corcoran, Sarah Schwartz, Katherine Treiber, Robert Green, Maria Norton, Michelle Mielke, Kathleen Piercy, Jeanne-Marie Leoutsakos, and John C. S. Breitner have no disclosures. NR 44 TC 60 Z9 62 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2011 VL 19 IS 6 BP 532 EP 542 DI 10.1097/JGP.0b013e3181faec23 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 766MP UT WOS:000290787300005 PM 21606896 ER PT J AU Gros, DF Yoder, M Tuerk, PW Lozano, BE Acierno, R AF Gros, Daniel F. Yoder, Matthew Tuerk, Peter W. Lozano, Brian E. Acierno, Ron TI Exposure Therapy for PTSD Delivered to Veterans via Telehealth: Predictors of Treatment Completion and Outcome and Comparison to Treatment Delivered in Person SO BEHAVIOR THERAPY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; PSYCHOMETRIC PROPERTIES; PROLONGED EXPOSURE; TELEPSYCHIATRY; VIDEOCONFERENCE; TELEMEDICINE; SERVICES; SCALES; SAMPLE AB Recent research has focused on the effectiveness of evidence-based psychotherapy delivered via telehealth services. Unfortunately to date, the majority of studies employ very small samples and limited predictor and moderator variables. To address these concerns and further replicate and extend the literature on telehealth, the present study investigated the effectiveness of 12-session exposure therapy delivered either via telehealth (n=62) or in person (n=27) in veterans with posttraumatic stress disorder (PTSD). Findings demonstrated that although older veterans and Vietnam veterans were more likely to complete the telehealth treatment, telehealth findings were not influenced by patient age, sex, race, combat theater, or disability status. Exposure therapy delivered via telehealth was effective in reducing the symptoms of PTSD, anxiety, depression, stress, and general impairment with large effect sizes. Interestingly, exposure therapy via telehealth was less effective than exposure therapy delivered in person; however, lack of random assignment to condition limits conclusions of differential effectiveness. Overall, these findings support the utility of telehealth services to provide effective, evidence-based psychotherapies. C1 [Gros, Daniel F.] Ralph H Johnson Vet Adm Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. Med Univ S Carolina, Charleston, SC USA. RP Gros, DF (reprint author), Ralph H Johnson Vet Adm Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu RI Schueter, nicos/A-3625-2014 NR 34 TC 70 Z9 71 U1 3 U2 11 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD JUN PY 2011 VL 42 IS 2 BP 276 EP 283 DI 10.1016/j.beth.2010.07.005 PG 8 WC Psychology, Clinical SC Psychology GA 763XT UT WOS:000290593700010 PM 21496512 ER PT J AU Ramsey, B Bai, T Newell, AH Troxell, M Park, B Olson, S Keenan, E Luoh, SW AF Ramsey, Betsy Bai, Tao Newell, Amy Hanlon Troxell, Megan Park, Byung Olson, Susan Keenan, Edward Luoh, Shiuh-Wen TI GRB7 protein over-expression and clinical outcome in breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Biomarker; Prognostic marker; Signal transduction; Gene amplification; Oncogenes; HER-2 gene; GRB7 gene ID IN-SITU HYBRIDIZATION; RECEPTOR-BOUND PROTEIN-7; HER-2 NEU ONCOGENE; AMERICAN-SOCIETY; ERBB2 AMPLICON; AMPLIFICATION; GENES; RECOMMENDATIONS; TUMORIGENESIS; ACTIVATION AB The growth factor receptor-bound protein-7 gene (GRB7) encodes a multi-domain signal transduction molecule. The purpose of this study was to examine the clinical significance of GRB7 protein expression in human breast cancer. Western blotting analysis of protein extracts from 563 annotated frozen breast tumors was performed. Expression status of GRB7 and HER-2 was correlated with clinical covariates and outcomes. Cox proportional hazards were used to identify factors associated with breast cancer-free interval. The median follow-up was 71 months. P values < 0.05 were considered statistically significant (two-sided). A discrepancy between HER-2 and GRB7 protein over-expression was observed. GRB7 protein over-expression was associated with negative estrogen and progesterone receptor status, higher tumor grade, larger primary tumor size, (more) axillary lymph node involvement, higher clinical stage, and shortened breast cancer-free interval. HER-2 protein over-expression was associated only with higher tumor grade. Multi-variate analysis revealed that GRB7 protein over-expression was an independent adverse prognostic factor for breast cancer-free interval (hazard ratio 1.69, 95% confidence interval 1.07-2.67; P = 0.024). The same was true of the subset of patients who did not receive any adjuvant systemic therapy (hazard ratio 1.68, 95% confidence interval 1.16-2.31; P = 0.0055). Using FISH analysis, 32/32 (100%; 95% CI 89-100%) tumors which over-expressed both HER-2 and GRB7 proteins and 1/35 (3%; 95% CI 0-15%) tumors with HER-2 but no GRB7 protein over-expression with Western blotting analysis demonstrated HER-2 gene amplification. GRB7 protein over-expression is an independent adverse prognostic factor in human breast cancer. C1 [Bai, Tao; Luoh, Shiuh-Wen] Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Ramsey, Betsy; Keenan, Edward] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Bai, Tao; Luoh, Shiuh-Wen] Portland VA Med Ctr, Portland, OR 97239 USA. [Newell, Amy Hanlon; Olson, Susan] Oregon Hlth & Sci Univ, Dept Med & Mol Genet, Portland, OR 97239 USA. [Troxell, Megan] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. [Park, Byung] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Ramsey, Betsy; Bai, Tao; Newell, Amy Hanlon; Troxell, Megan; Park, Byung; Olson, Susan; Keenan, Edward; Luoh, Shiuh-Wen] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. RP Luoh, SW (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, 3181 SW Sam Jackson Pk Rd,MC L586, Portland, OR 97239 USA. EM luohs@ohsu.edu OI /0000-0003-3516-7516 FU Department of Veterans Affairs; Portland VA Research Foundation; OHSU; OHSU Foundation FX The work is supported by Department of Veterans Affairs, Portland VA Research Foundation, OHSU Presidential Bridge Award, and OHSU Foundation. We are grateful to the technical assistance provided by the Histology Shared Resources at the Knight Cancer Institute, OHSU. NR 31 TC 19 Z9 20 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2011 VL 127 IS 3 BP 659 EP 669 DI 10.1007/s10549-010-1010-0 PG 11 WC Oncology SC Oncology GA 766UH UT WOS:000290811500008 PM 20635137 ER PT J AU Pelosi, P Ferguson, ND Frutos-Vivar, F Anzueto, A Putensen, C Raymondos, K Apezteguia, C Desmery, P Hurtado, J Abroug, F Elizalde, J Tomicic, V Cakar, N Gonzalez, M Arabi, Y Moreno, R Esteban, A AF Pelosi, Paolo Ferguson, Niall D. Frutos-Vivar, Fernando Anzueto, Antonio Putensen, Christian Raymondos, Konstantinos Apezteguia, Carlos Desmery, Pablo Hurtado, Javier Abroug, Fekri Elizalde, Jose Tomicic, Vinko Cakar, Nahit Gonzalez, Marco Arabi, Yaseen Moreno, Rui Esteban, Andres CA Ventila Study Grp TI Management and outcome of mechanically ventilated neurologic patients SO CRITICAL CARE MEDICINE LA English DT Article DE mechanical ventilation; stroke; brain trauma; outcome; mortality; epidemiology ID TRAUMATIC BRAIN-INJURY; ACUTE LUNG INJURY; ANEURYSMAL SUBARACHNOID HEMORRHAGE; RESPIRATORY-DISTRESS-SYNDROME; INTENSIVE-CARE-UNIT; SEVERE HEAD-INJURY; EXTRACRANIAL COMPLICATIONS; INTRACEREBRAL HEMORRHAGE; MEDICAL COMPLICATIONS; ORGAN DYSFUNCTION AB Objective: To describe and compare characteristics, ventilatory practices, and associated outcomes among mechanically ventilated patients with different types of brain injury and between neurologic and nonneurologic patients. Design: Secondary analysis of a prospective, observational, and multicenter study on mechanical ventilation. Setting: Three hundred forty-nine intensive care units from 23 countries. Patients: We included 552 mechanically ventilated neurologic patients (362 patients with stroke and 190 patients with brain trauma). For comparison we used a control group of 4,030 mixed patients who were ventilated for nonneurologic reasons. Interventions: None. Measurements and Main Results: We collected demographics, ventilatory settings, organ failures, and complications arising during ventilation and outcomes. Multivariate logistic regression analysis was performed with intensive care unit mortality as the dependent variable. At admission, a Glasgow Coma Scale score <= 8 was observed in 68% of the stroke, 77% of the brain trauma, and 29% of the nonneurologic patients. Modes of ventilation and use of a lung-protective strategy within the first week of mechanical ventilation were similar between groups. In comparison with nonneurologic patients, patients with neurologic disease developed fewer complications over the course of mechanical ventilation with the exception of a higher rate of ventilator-associated pneumonia in the brain trauma cohort. Neurologic patients showed higher rates of tracheotomy and longer duration of mechanical ventilation. Mortality in the intensive care unit was significantly (p <.001) higher in patients with stroke (45%) than in brain trauma (29%) and nonneurologic disease (30%). Factors associated with mortality were: stroke (in comparison to brain trauma), Glasgow Coma Scale score on day 1, and severity at admission in the intensive care unit. Conclusions: In our study, one of every five mechanically ventilated patients received this therapy as a result of a neurologic disease. This cohort of patients showed a higher mortality rate than nonneurologic patients despite a lower incidence of extracerebral organ dysfunction. (Crit Care Med 2011; 39: 1482-1492) C1 [Pelosi, Paolo] Univ Genoa, Dipartimento Sci Chirurg Diagnost Integrate, Genoa, Italy. [Ferguson, Niall D.] Univ Hlth Network, Interdept Div Crit Care Med, Toronto, ON, Canada. [Ferguson, Niall D.] Univ Hlth Network, Dept Med, Div Respirol, Toronto, ON, Canada. [Ferguson, Niall D.] Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Frutos-Vivar, Fernando; Esteban, Andres] Hosp Univ Getafe, Madrid, Spain. [Frutos-Vivar, Fernando; Esteban, Andres] CIBER Enfermedades Resp, Madrid, Spain. [Anzueto, Antonio] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Putensen, Christian] Univ Bonn, Dept Anesthesiol & Intens Care Med, D-5300 Bonn, Germany. [Raymondos, Konstantinos] Hannover Med Sch, D-30623 Hannover, Germany. [Apezteguia, Carlos] Hosp Prof A Posadas, Buenos Aires, DF, Argentina. [Desmery, Pablo] Sanat Mitre, Buenos Aires, DF, Argentina. [Hurtado, Javier] Hosp Clin Montevideo, Montevideo, Uruguay. [Elizalde, Jose] Hosp ABC, Mexico City, DF, Mexico. [Tomicic, Vinko] Clin Las Lilas, Santiago, Chile. [Cakar, Nahit] Istanbul Fac Med, Istanbul, Turkey. [Gonzalez, Marco] Clin Medellin, Medellin, Colombia. [Gonzalez, Marco] Univ Pontificia Bolivariana, Medellin, Colombia. [Arabi, Yaseen] King Abdul Aziz Med City, Riyadh, Saudi Arabia. [Moreno, Rui] Hosp Santo Antonio Capuchos, Lisbon, Portugal. RP Pelosi, P (reprint author), Univ Genoa, Dipartimento Sci Chirurg Diagnost Integrate, Genoa, Italy. EM aesteban@ucigetafe.com RI Pesenti, Antonio/H-7483-2012; koca, ugur/F-1265-2016; Malbrain, Manu/B-3680-2017 OI CHIUMELLO, DAVIDE ALBERTO/0000-0001-9260-3930; koca, ugur/0000-0002-2949-4265; Malbrain, Manu/0000-0002-1816-5255; Severgnini, Paolo/0000-0001-8027-0059; Darmon, Michael/0000-0003-4198-8038; Frutos-Vivar, Fernando/0000-0002-4648-9636; Ost, David/0000-0001-6351-5552; Ferguson, Niall/0000-0002-6213-5264 FU CIBER; Instituto de Salud Carlos III, Spain; Canadian Institutes of Health Research New Investigator Award (Ottawa, Canada) FX Funded by CIBER Enfermedades Respiratorias from Instituto de Salud Carlos III, Spain.; N.D.F. is supported by a Canadian Institutes of Health Research New Investigator Award (Ottawa, Canada). The remaining authors have not disclosed any potential conflicts of interest. NR 43 TC 35 Z9 39 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2011 VL 39 IS 6 BP 1482 EP 1492 DI 10.1097/CCM.0b013e31821209a8 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 765NM UT WOS:000290715000036 PM 21378554 ER PT J AU Telander, DG Morales, SA Mareninov, S Forward, K Gordon, LK AF Telander, David G. Morales, Shawn A. Mareninov, Sergey Forward, Krisztina Gordon, Lynn K. TI Epithelial Membrane Protein-2 (EMP2) and Experimental Proliferative Vitreoretinopathy (PVR) SO CURRENT EYE RESEARCH LA English DT Article DE Epithelial membrane protein 2; Fibrosis; Integrin regulation; Proliferative vitreoretinopathy; Retina; Rhegmatogenous retinal detachment; Retinal pigment epithelium; Therapy; Vitreous membranes ID EXPERIMENTAL RETINAL-DETACHMENT; COLLAGEN GEL CONTRACTION; MESENCHYMAL TRANSITION; SURFACE EXPRESSION; EXPERIMENTAL-MODEL; CELL-DEATH; PATHWAY; ALKYLPHOSPHOCHOLINES; ACTIVATION; SILICONE AB Purpose: Proliferative vitreoretinopathy (PVR) is believed to result in part from de-differentiation of retinal pigment epithelium (RPE) with cellular migration in the vitreous cavity, membrane formation, and contraction in an aberrant wound-healing strategy. In an in vitro collagen-gel contraction assay, epithelial membrane protein 2 (EMP2) controls contraction through activation of focal adhesion kinase (FAK) in a RPE cell line (ARPE-19). The purpose of this study was to investigate how blocking or altering the level of EMP2 expression changed clinical PVR in an in vivo model. Methods: Using the ARPE-19 cell line, the levels of EMP2 modulated through stable transfections of an EMP2 overexpressing construct, EMP2 ribozyme, or vector alone. These transfected cell lines were used in a rabbit model of PVR. The severity of PVR was classified by two masked observers. An EMP2 blocking antibody was also used to decrease functional EMP2 in the PVR model. Immunohistochemistry was used to evaluate EMP2 expression in vivo. Results: The transfectants with lower levels of EMP2 had significantly less PVR severity than the degree of PVR induced by wild-type cells (p = 0.05). Also, the transfectants with a low-level of EMP2 expression showed a strong trend of less PVR severity than the high-levels EMP2 transfectants (p = 0.06). Blocking EMP2 with a specific polyclonal antibody significantly decreased the level of PVR severity (p = 0.02). PVR membranes were found to be positive for EMP2 expression. Conclusions: These in vivo studies support a direct correlation between EMP2 expression and severity of PVR. These results validate the potential for controlling RPE biology through a change in EMP2 expression, and provide a potential therapeutic target for this disease. C1 [Telander, David G.; Forward, Krisztina] Univ Calif Davis, Dept Ophthalmol, Sacramento, CA 95817 USA. [Morales, Shawn A.; Gordon, Lynn K.] Univ Calif Los Angeles, Jules Stein Eye Inst, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Mareninov, Sergey] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Gordon, Lynn K.] Greater Los Angeles VA Healthcare syst, Los Angeles, CA USA. RP Telander, DG (reprint author), UC Davis, Retina Div, Dept Ophthalmol & Visual Sci, 4860 Y St,Suite 2400, Sacramento, CA 95817 USA. EM dgtelander@ucdavis.edu FU Research to Prevent Blindness; Foundation Fighting Blindness; Veterans Administration; NIH NEI [1R01EY019909-01A1] FX The authors acknowledge support via unrestricted departmental funds from Research to Prevent Blindness, Foundation Fighting Blindness (DGT), and a Veterans Administration Merit Grant (LKG). NIH NEI R01 Grant Number: 1R01EY019909-01A1. NR 34 TC 8 Z9 8 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD JUN PY 2011 VL 36 IS 6 BP 546 EP 552 DI 10.3109/02713683.2011.561468 PG 7 WC Ophthalmology SC Ophthalmology GA 765SE UT WOS:000290728100008 PM 21591864 ER PT J AU Jessup, JA Zhang, LL Presley, TD Kim-Shapiro, DB Wang, H Chen, AF Groban, L AF Jessup, Jewell A. Zhang, Lili Presley, Tennille D. Kim-Shapiro, Daniel B. Wang, Hao Chen, Alex F. Groban, Leanne TI Tetrahydrobiopterin Restores Diastolic Function and Attenuates Superoxide Production in Ovariectomized mRen2.Lewis Rats SO ENDOCRINOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; PREVENTS ENDOTHELIAL DYSFUNCTION; MYOCARDIAL REPERFUSION INJURY; LEFT-VENTRICULAR HYPERTROPHY; ESTROGEN-RECEPTOR SUBTYPES; HEART-FAILURE; OXIDATIVE STRESS; 17-BETA-ESTRADIOL ANTAGONIZES; VASCULAR TETRAHYDROBIOPTERIN; POSTMENOPAUSAL WOMEN AB After oophorectomy, mRen2.Lewis rats exhibit diastolic dysfunction associated with elevated superoxide, increased cardiac neuronal nitric oxide synthase (nNOS) expression, and diminished myocardial tetrahydrobiopterin (BH4) content, effects that are attenuated with selective nNOS inhibition. BH4 is an essential cofactor of nNOS catalytic activity leading to nitric oxide production. Therefore, we assessed the effect of 4wk BH4 supplementation on diastolic function and left ventricular (LV) remodeling in oophorectomized mRen2.Lewis rats compared with sham-operated controls. Female mRen2.Lewis rats underwent either bilateral ovariectomy (OVX) (n = 19) or sham operation (n = 13) at 4wk of age. Beginning at 11 wk of age, OVX rats were randomized to receive either BH4 (10 mg/kg.d) or saline, whereas the sham rats received saline via sc mini-pumps. Loss of ovarian hormones reduced cardiac BH4 when compared with control hearts; this was associated with impaired myocardial relaxation, augmented filling pressures, increased collagen deposition, and thickened LV walls. Additionally, superoxide production increased and nitric oxide decreased in hearts from OVX compared with sham rats. Chronic BH4 supplementation after OVX improved diastolic function and attenuated LV remodeling while restoring myocardial nitric oxide release and preventing reactive oxygen species generation. These data indicate that BH4 supplementation protects against the adverse effects of ovarian hormonal loss on diastolic function and cardiac structure in mRen2.Lewis rats by restoring myocardial NO release and mitigating myocardial O-2(-) generation. Whether BH4 supplementation is a therapeutic option for the management of diastolic dysfunction in postmenopausal women will require direct testing in humans. (Endocrinology 152: 2428-2436, 2011) C1 [Wang, Hao; Groban, Leanne] Wake Forest Univ, Dept Anesthesiol, Sch Med, Winston Salem, NC 27157 USA. [Jessup, Jewell A.; Groban, Leanne] Wake Forest Univ, Dept Physiol, Sch Med, Winston Salem, NC 27157 USA. [Jessup, Jewell A.; Groban, Leanne] Wake Forest Univ, Dept Pharmacol, Sch Med, Winston Salem, NC 27157 USA. [Zhang, Lili; Chen, Alex F.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15206 USA. Vet Affairs Pittsburgh Healthcare Syst, Vasc Surg Res, Pittsburgh, PA 15206 USA. [Presley, Tennille D.; Kim-Shapiro, Daniel B.] Wake Forest Univ, Dept Phys, Winston Salem, NC 27106 USA. [Presley, Tennille D.; Kim-Shapiro, Daniel B.] Wake Forest Univ, Translat Sci Ctr, Winston Salem, NC 27106 USA. RP Groban, L (reprint author), Wake Forest Univ, Dept Anesthesiol, Sch Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM lgroban@wfubmc.edu FU National Institutes of Health [R01-AG033727-01, KO8-AG026764-05, HL-058091, R01 GM077352, 2PO1 HL-051952]; American Heart Association [0855601GH] FX This work was supported by grants from the National Institutes of Health R01-AG033727-01 (to L.G.), KO8-AG026764-05 Paul Beeson award (to L.G.), HL-058091 (to D.B.K.-S.), R01 GM077352 (to A.F.C.), 2PO1 HL-051952 (to C.M. Ferrario), and American Heart Association Grant-in-Aid 0855601GH (to A.F.C.). Support was limited to funding. NR 58 TC 11 Z9 12 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2011 VL 152 IS 6 BP 2428 EP 2436 DI 10.1210/en.2011-0061 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 766MY UT WOS:000290788500029 PM 21427216 ER PT J AU Chirinos, JA Kips, JG Roman, MJ Medina-Lezama, J Li, Y Woodiwiss, AJ Norton, GR Yasmin Van Bortel, L Wang, JG Cockcroft, JR Devereux, RB Wilkinson, IB Segers, P McEniery, CM AF Chirinos, Julio A. Kips, Jan G. Roman, Mary J. Medina-Lezama, Josefina Li, Yan Woodiwiss, Angela J. Norton, Gavin R. Yasmin Van Bortel, Luc Wang, Ji-Guang Cockcroft, John R. Devereux, Richard B. Wilkinson, Ian B. Segers, Patrick McEniery, Carmel M. TI Ethnic Differences in Arterial Wave Reflections and Normative Equations for Augmentation Index SO HYPERTENSION LA English DT Article DE wave reflections; augmentation index; ethnicity ID LEFT-VENTRICULAR HYPERTROPHY; REFERENCE VALUES; BLOOD-PRESSURE; PULSE-WAVE; CARDIOVASCULAR-DISEASE; VASCULAR-DISEASE; POPULATION; STIFFNESS; MEN; HEMODYNAMICS AB Data regarding ethnic differences in wave reflections, which markedly affect the central pressure profile, are very limited. Furthermore, because age, heart rate, and body height are strong determinants of augmentation index, relating single measurements to normative data (in which augmentation index values correspond with average population values of its determinants) is challenging. We studied subject-level data from 10 550 adults enrolled in large population-based studies. In a healthy reference sample (n = 3497), we assessed ethnic differences in augmentation index (ratio of second/first systolic peaks) and generated equations for adjusted z scores, allowing for a standardized comparison between individual augmentation index measurements and the normative population mean from subjects of the same age, sex, ethnic population, body height, and heart rate. After adjustment for age, body height, heart rate, and mean arterial pressure, African blacks (women: 154%; men: 138%) and Andean Hispanics (women: 152%; men: 133%) demonstrated higher central (aortic) augmentation index values than British whites (women: 140%; men: 128%), whereas American Indians (women: 133%; men: 122%) demonstrated lower augmentation index (all P < 0.0001), without significant differences between Chinese and British whites. Similar results were found for radial augmentation index. Nonlinear ethnic/sex-specific equations for z scores were successfully generated to adjust individual augmentation index values for age, body height, and heart rate. Marked ethnic differences in augmentation index exist, which may contribute to ethnic differences in hypertensive organ damage. Our study provides normative data that can be used to complement the interpretation of individual hemodynamic assessments among men and women of various ethnic populations, after removing the effect of various physiological determinants. (Hypertension. 2011;57:1108-1116.). Online Data Supplement C1 [Chirinos, Julio A.] Univ Penn, Div Cardiol, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Kips, Jan G.; Van Bortel, Luc; Segers, Patrick] Univ Ghent, IBiTech, B-9000 Ghent, Belgium. Univ Ghent, Heymans Inst Pharmacol, B-9000 Ghent, Belgium. [Roman, Mary J.; Devereux, Richard B.] Weill Cornell Med Coll, Div Cardiol, New York, NY USA. [Medina-Lezama, Josefina] Santa Maria Catholic Univ, Santa Maria Res Inst, Arequipa, Peru. [Li, Yan; Wang, Ji-Guang] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Hypertens, Ctr Epidemiol Studies & Clin Trials,Ruijin Hosp, Shanghai 200030, Peoples R China. [Woodiwiss, Angela J.] Univ Witwatersrand, Fac Hlth Sci, Sch Physiol, Cardiovasc Pathophysiol & Genom Res Unit, Johannesburg, South Africa. [Yasmin; Wilkinson, Ian B.; McEniery, Carmel M.] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge CB2 2QQ, England. [Cockcroft, John R.] Univ Cardiff, Dept Cardiol, Cardiff, S Glam, Wales. RP Chirinos, JA (reprint author), Rm 8B111,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM julio.chirinos@uphs.upenn.edu FU National Heart, Lung, and Blood Institute [U01-HL65521]; South African Medical Research Council; National Research Foundation of South Africa; University Research Council of the University of the Witwatersrand; Santa Maria Research Institute (AQP/Peru); National Natural Science Foundation of China [30871360, 30871081]; Ministry of Science and Technology, Beijing, China [2006BAI01A03]; Shanghai Commissions of Science and Technology [07JC14047, 06QA14043, 07ZZ32, 08SG20]; Shanghai Shenkang Hospital Development Centre [SHDC12007318]; Shanghai Jiaotong University School of Medicine; European Union [LSHM-CT-2006-037093, HEALTH-F4-2007-201550] FX This study was supported by National Heart, Lung, and Blood Institute grant U01-HL65521; the South African Medical Research Council; the National Research Foundation of South Africa; the University Research Council of the University of the Witwatersrand; the Santa Maria Research Institute (AQP/Peru); the National Natural Science Foundation of China (grants 30871360 and 30871081); the Ministry of Science and Technology (grant 2006BAI01A03), Beijing, China; the Shanghai Commissions of Science and Technology (grant 07JC14047 and the "Rising Star" program 06QA14043) and Education (grant 07ZZ32 and the "Dawn" project 08SG20); the Shanghai Shenkang Hospital Development Centre (grant SHDC12007318); Shanghai Jiaotong University School of Medicine (a grant of Distinguished Young Investigators to Y.L.); and the European Union (grants LSHM-CT-2006-037093 and HEALTH-F4-2007-201550). NR 27 TC 48 Z9 48 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 2011 VL 57 IS 6 BP 1108 EP U153 DI 10.1161/HYPERTENSIONAHA.110.166348 PG 13 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 765MI UT WOS:000290710800023 PM 21536986 ER PT J AU Zhao, H Goetz, MB AF Zhao, Hui Goetz, Matthew Bidwell TI Complications of HIV infection in an ageing population: challenges in managing older patients on long-term combination antiretroviral therapy SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Review DE immunocompromised host; epidemiology; age ID HUMAN-IMMUNODEFICIENCY-VIRUS; MYOCARDIAL-INFARCTION RATES; BONE-MINERAL DENSITY; HEALTH-CARE-SYSTEM; D-A-D; DIABETES-MELLITUS; NAIVE PATIENTS; RISK-FACTORS; CELL COUNT; RANDOMIZED-TRIAL AB With the use of combination antiretroviral therapy, the proportion of HIV-infected patients over age 50 has greatly increased. The rate of progression of untreated HIV disease, response to therapy and complicating effects of co-morbidities differ in older versus younger patients. Compared with younger individuals, older untreated HIV patients demonstrate faster rates of CD4+ cell loss and more rapid progression to AIDS and death. With treatment, older patients have a better virological response, but a less robust immunological response. The treatment of older HIV-infected patients is further complicated by pre-existing co-morbid conditions including cardiovascular, hepatic and metabolic complications that may be exacerbated by the effects of HIV infection per se, modest immunodeficiency (i.e. at CD4+ counts >350 cells/mm(3)), and the metabolic and other adverse effects of combination antiretroviral therapy. Based on these considerations guidelines for the treatment of HIV-infected patients state that increased age is a consideration in initiating antiretroviral therapy in persons with >350-500 CD4+ cells/mm(3). C1 [Zhao, Hui; Goetz, Matthew Bidwell] VA Greater Angeles Healthcare Syst, Infect Dis Sect, Dept Med, Los Angeles, CA 90073 USA. [Zhao, Hui] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Goetz, MB (reprint author), VA Greater Angeles Healthcare Syst, Infect Dis Sect 111F, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM matthew.goetz@va.gov OI Goetz, Matthew/0000-0003-4542-992X NR 67 TC 8 Z9 8 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUN PY 2011 VL 66 IS 6 BP 1210 EP 1214 DI 10.1093/jac/dkr058 PG 5 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 763VM UT WOS:000290587800003 PM 21421583 ER PT J AU Mamtani, M Mummidi, S Ramsuran, V Pham, MH Maldonado, R Begum, K Valera, MS Sanchez, R Castiblanco, J Kulkarni, H Ndung'u, T He, WJ Anaya, JM Ahuja, SK AF Mamtani, Manju Mummidi, Srinivas Ramsuran, Veron Pham, Minh-Hieu Maldonado, Robert Begum, Kazi Valera, Maria Soledad Sanchez, Racquel Castiblanco, John Kulkarni, Hemant Ndung'u, Thumbi He, Weijing Anaya, Juan Manuel Ahuja, Sunil K. TI Influence of Variations in CCL3L1 and CCR5 on Tuberculosis in a Northwestern Colombian Population SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; RECEPTOR 5 GENE; HIV-1; EXPRESSION; SUSCEPTIBILITY; POLYMORPHISM; ASSOCIATION; HAPLOTYPES; CHEMOKINES; GENOTYPES AB We investigated the association of polymorphisms in CCR5, the major human immunodeficiency virus (HIV)-1 coreceptor, and copy number of its potent ligand CCL3L1 with tuberculosis in 298 individuals from Colombia. The CCR5-HHD haplotype, a known genetic determinant of increased susceptibility to HIV-AIDS, and a high copy number of CCL3L1, a known genetic determinant of enhanced CCL3/CCL3L1 chemokine expression, each associated with presence of tuberculosis. Furthermore, CCR5-HHD was associated with higher CCR5 gene and surface expression. These results substantiate the strong link between the pro-inflammatory effects of CCR5 and its ligands with active tuberculosis and suggest that chemokine-chemokine receptor genetic determinants may influence tuberculosis in addition to HIV/AIDS. C1 [Mamtani, Manju; Mummidi, Srinivas; Pham, Minh-Hieu; Maldonado, Robert; Begum, Kazi; Valera, Maria Soledad; Sanchez, Racquel; Castiblanco, John; Kulkarni, Hemant; He, Weijing; Ahuja, Sunil K.] S Texas Vet Hlth Care Syst, Vet Adm Ctr AIDS & HIV Infect 1, San Antonio, TX USA. [Mamtani, Manju; Mummidi, Srinivas; Pham, Minh-Hieu; Maldonado, Robert; Begum, Kazi; Valera, Maria Soledad; Sanchez, Racquel; Castiblanco, John; Kulkarni, Hemant; He, Weijing; Ahuja, Sunil K.] S Texas Vet Hlth Care Syst, Ctr Personalized Med, San Antonio, TX USA. [Mamtani, Manju; Mummidi, Srinivas; Pham, Minh-Hieu; Maldonado, Robert; Begum, Kazi; Valera, Maria Soledad; Sanchez, Racquel; Castiblanco, John; Kulkarni, Hemant; He, Weijing; Ahuja, Sunil K.] Univ Texas San Antonio, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Ramsuran, Veron; Ndung'u, Thumbi] Univ KwaZulu Natal, CAPRISA, Nelson R Mandela Sch Med, Durban, South Africa. [Ramsuran, Veron; Ndung'u, Thumbi] Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, Durban, South Africa. [Anaya, Juan Manuel] Corp Invest Biol, Cellular Biol & Immunogenet Unit, Medellin, Colombia. [Anaya, Juan Manuel] Univ Rosario, Sch Med, Bogota, Colombia. RP Ahuja, SK (reprint author), VA Ctr Personalized Med, San Antonio, TX 78229 USA. EM ahujas@uthscsa.edu RI CASTIBLANCO, JOHN/B-6599-2009; Mummidi, Srinivas/C-1004-2008; Anaya, Juan-Manuel/J-1960-2016 OI CASTIBLANCO, JOHN/0000-0002-7965-9822; Mummidi, Srinivas/0000-0002-4068-6380; Anaya, Juan-Manuel/0000-0002-6444-1249; Universidad del Rosario, Biblioteca/0000-0003-3491-9392; CASTIBLANCO, JOHN/0000-0003-2556-3697; Ndung'u, Thumbi/0000-0003-2962-3992 FU Veterans Administration Center on AIDS and HIV infection of the South Texas Veterans Health Care System; NIH [R37046326]; VA MERIT award; Elizabeth Glaser Scientist Award; Burroughs Wellcome Clinical Scientist Award in Translational Research; Doris Duke Distinguished Clinical Scientist Award FX This work was supported by the Veterans Administration Center on AIDS and HIV infection of the South Texas Veterans Health Care System, and the NIH (R37046326), a VA MERIT award, the Elizabeth Glaser Scientist Award, the Burroughs Wellcome Clinical Scientist Award in Translational Research, and the Doris Duke Distinguished Clinical Scientist Award to S. K. A. The work was also supported by a VA MERIT award to S. M. NR 16 TC 13 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2011 VL 203 IS 11 BP 1590 EP 1594 DI 10.1093/infdis/jir145 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 767LT UT WOS:000290858800013 PM 21592988 ER PT J AU Thompson, EM Dosa, E Kraemer, DF Neuwelt, EA AF Thompson, Eric M. Dosa, Edit Kraemer, Dale F. Neuwelt, Edward A. TI Correlation of MRI sequences to assess progressive glioblastoma multiforme treated with bevacizumab SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Bevacizumab; Macdonald criteria; FLAIR; Progressive malignant glioma ID RECURRENT MALIGNANT GLIOMA; GRADE GLIAL TUMORS; PHASE-II; IRINOTECAN; EFFICACY; MODEL; CARBOPLATIN; SURVIVAL; CRITERIA; VOLUME AB In the context of bevacizumab therapy for the treatment of progressive malignant gliomas, it is currently unclear how different magnetic resonance imaging (MRI) sequences correlate with each other over time. The objective of this study was to determine if a reliable and predictable relationship over time exists between post-gadolinium based contrast agent T1-weighted (T1 + GBCA), T2-weighted, and FLAIR MRI in patients with progressive glioblastoma multiforme (GBM) receiving bevacizumab and chemotherapy. The MRI lesion volumes of 10 patients with progressive GBM that received bevacizumab plus chemotherapy were manually calculated by two independent reviewers. T2 and FLAIR volumes were analyzed by analysis of covariance (ANCOVA) as a function of T1 + GBCA lesion enhancement volume, reviewer, and time interval between MRI acquisitions. Pearson product moment correlation (r) was used to compare pre and post treatment volumes for the group of 10 patients and for each individual patient over their treatment course. ANCOVA demonstrated a significant association between T1 + GBCA and T2-weighted volumes (P = 0.0006) and between T1 + GBCA and FLAIR volumes (P < 0.0001). These associations remained constant over time. The correlation between T1 + GBCA and both T2-weighted and FLAIR volumes improved after bevacizumab treatment. Individual correlations between T1 + GBCA and FLAIR were strong (r a parts per thousand yen 0.63) with one exception, while correlations between T1 + GBCA and T2 were more variable (r = 0.18-0.99). These findings suggest that FLAIR MRI should be evaluated in addition to T1 + GBCA MRI when evaluating GBM responses. C1 [Thompson, Eric M.; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR 97239 USA. [Dosa, Edit; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Kraemer, Dale F.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Kraemer, Dale F.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. [Kraemer, Dale F.] Oregon Hlth & Sci Univ, Dept Pharm Practice, Oregon State Univ, Coll Pharm, Portland, OR 97239 USA. [Neuwelt, Edward A.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR 97239 USA. EM neuwelte@ohsu.edu NR 22 TC 6 Z9 6 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JUN PY 2011 VL 103 IS 2 BP 353 EP 360 DI 10.1007/s11060-010-0397-0 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 766IB UT WOS:000290773100019 PM 20848300 ER PT J AU Woodard, LD Urech, T Landrum, CR Wang, D Petersen, LA AF Woodard, LeChauncy D. Urech, Tracy Landrum, Cassie R. Wang, Degang Petersen, Laura A. TI Impact of Comorbidity Type on Measures of Quality for Diabetes Care SO MEDICAL CARE LA English DT Article DE diabetes mellitus; quality of health care; comorbidity ID UNITED-STATES; PERFORMANCE-MEASURES; HYPERTENSION; MEDICATION; IMPROVEMENT; DEPRESSION; PREVALENCE; ADHERENCE; OUTCOMES; DISEASE AB Objective: Studies provide conflicting results about the impact of comorbid conditions on the quality of chronic illness care. We assessed the effect of comorbidity type (concordant, discordant, or both) on the receipt of guideline-recommended care among patients with diabetes. Research Design: Patients were assigned to 1 of 4 condition groups: diabetes-concordant (hypertension, ischemic heart disease, hyperlipidemia), and/or diabetes-discordant (arthritis, depression, chronic obstructive pulmonary disease) conditions, or neither. We evaluated hemoglobin A1c, blood pressure, and low-density lipoprotein cholesterol readings at index and measured overall good quality of diabetes care, including a 6-month follow-up interval. We assessed the effect of condition group on overall good quality of care with logistic regression and generalized ordered logistic regression. Results: We assigned 35,872 patients to the diabetes comorbid condition groups, ranging from 2.0% in the discordant-only group to 58.0% in the concordant-only group. Patients with both types of conditions were more likely than those with no comorbidities to receive overall good quality for glycemic [odds ratio (OR), 2.13; 95% confidence interval (CI), 1.86-2.41], blood pressure (OR, 1.62; 95% CI, 1.40-1.84), and low-density lipoprotein cholesterol (OR, 3.57; 95% CI, 3.08-4.05) control within 6 months of an index visit. They were also more likely to receive overall good quality for all 3 quality measures combined (OR, 2.17; 95% CI, 1.96-2.39). Conclusions: Patients with the greatest clinical complexity were more likely than less complex patients to receive high quality diabetes care, suggesting that increased complexity does not necessarily predispose chronically ill patients to receiving poorer care. However, caution should be used in treating certain patient groups, such as the elderly, for whom adherence to multiple condition-specific guidelines may lack benefit or cause harm. C1 [Woodard, LeChauncy D.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Hlth Policy & Qual Program, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP Woodard, LD (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Hlth Policy & Qual Program, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM woodard.lechauncy@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [PPO 09-316, IIR 04-349]; National Institutes of Health [R01 HL079173-01]; Houston VA HSR&D Center of Excellence [HFP90-020]; Dr Petersen was a Robert Wood Johnson Foundation [045444]; American Heart Association [0540043N] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, (PPO 09-316, PI LeChauncy D. Woodard, MD, MPH), (IIR 04-349, PI Laura A. Petersen, MD, MPH), National Institutes of Health (R01 HL079173-01, PI Laura A. Petersen, MD, MPH), and Houston VA HSR&D Center of Excellence HFP90-020 (PI Laura A. Petersen, MD, MPH). Dr Petersen was a Robert Wood Johnson Foundation Generalist Physician Faculty Scholar (grant number 045444) and an American Heart Association Established Investigator Awardee (grant number 0540043N) at the time this work was conducted. Dr Woodard is an assistant professor at the Michael E. DeBakey VA Medical Center Health Services Research and Development Center of Excellence, Houston, Texas. The funding sources played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 25 TC 30 Z9 30 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2011 VL 49 IS 6 BP 605 EP 610 DI 10.1097/MLR.0b013e31820f0ed0 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 763MS UT WOS:000290563600013 PM 21422952 ER PT J AU Newcomb, LW Koltyn, KF Morgan, WP Cook, DB AF Newcomb, Lauren W. Koltyn, Kelli F. Morgan, William P. Cook, Dane B. TI Influence of Preferred versus Prescribed Exercise on Pain in Fibromyalgia SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE PHYSICAL ACTIVITY; CHRONIC PAIN; RPE; EXERCISE PRESCRIPTION ID STRESS-INDUCED ANALGESIA; CHRONIC-FATIGUE-SYNDROME; PHYSICAL-ACTIVITY; AEROBIC EXERCISE; IMPACT QUESTIONNAIRE; MECHANISMS; CONTRACTION; THRESHOLDS; PERCEPTION; RESPONSES AB NEWCOMB, L. W., K. F. KOLTYN, W. P. MORGAN, and D. B. COOK. Influence of Preferred versus Prescribed Exercise on Pain in Fibromyalgia. Med. Sci. Sports Exerc., Vol. 43, No. 6, pp. 1106-1113, 2011. Purpose: The purpose of this study was to examine the influence of a preferred-versus a prescribed-intensity exercise session on pain in women with fibromyalgia (FM). Methods: Twenty-one women with FM (mean age = 44 yr) completed two randomly assigned exercise sessions consisting of 20 min of cycle ergometry at a self-selected intensity and a prescribed intensity. Experimental pain perception was assessed before and after aerobic exercise. During exercise, HR, watts, RPE, and muscle pain were assessed every 5 min. Clinical pain was assessed with the Short-Form McGill Pain Questionnaire (SF-MPQ) immediately and 24, 48, 72, and 96 h after exercise. Data were analyzed with repeated-measures ANOVA. Results: Women with FM preferred a lower intensity of exercise than what was prescribed as indicated by significantly lower HR, watts, and RPE responses (P < 0.05). Muscle pain in the legs, however, was similar in the two conditions and significantly increased during exercise (P < 0.05). Pain thresholds and pain tolerances increased significantly after exercise, whereas peak pain ratings decreased after exercise (P < 0.05). Furthermore, pain (SF-MPQ) in the follow-up period was found to be lower than baseline (P < 0.05). Conclusions: It is concluded that the women with FM who participated in this study experienced significant improvements in pain after exercise. The results from this study are novel and indicate that recommendations for exercise prescription for individuals with FM should consider the preferred-intensity exercise model as a strategy to reduce pain. C1 [Newcomb, Lauren W.; Koltyn, Kelli F.; Morgan, William P.; Cook, Dane B.] Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA. [Cook, Dane B.] William S Middleton Mem Vet Adm Med Ctr, Res Serv, Madison, WI USA. RP Cook, DB (reprint author), Univ Wisconsin, Dept Kinesiol, 2000 Observ Dr, Madison, WI 53706 USA. EM dcook@education.wisc.edu FU Diane and Donald Masterson Gift Fund FX This study was supported by the Diane and Donald Masterson Gift Fund. NR 47 TC 15 Z9 15 U1 3 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUN PY 2011 VL 43 IS 6 BP 1106 EP 1113 DI 10.1249/MSS.0b013e3182061b49 PG 8 WC Sport Sciences SC Sport Sciences GA 764TW UT WOS:000290657300025 PM 21085031 ER PT J AU Geser, F Malunda, JA Hurtig, HI Duda, JE Wenning, GK Gilman, S Low, PA Lee, VMY Trojanowski, JQ AF Geser, F. Malunda, J. A. Hurtig, H. I. Duda, J. E. Wenning, G. K. Gilman, S. Low, P. A. Lee, V. M. -Y. Trojanowski, J. Q. TI TDP-43 pathology occurs infrequently in multiple system atrophy SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Article DE 43-kDa transactive response DNA-binding protein; multiple system atrophy ID AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; MOTOR-NEURON DISEASE; GROUP EMSA-SG; ALZHEIMERS-DISEASE; CYTOPLASMIC INCLUSIONS; ALPHA-SYNUCLEIN; WHITE-MATTER; DNA-BINDING; DEMENTIA AB Aims and Methods: The alpha-synucleinopathy multiple system atrophy (MSA) and diseases defined by pathological 43-kDa transactive response DNA-binding protein (TDP-43) or fused in sarcoma (FUS) aggregates such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration show overlapping clinico-pathological features. Consequently, we examined MSA for evidence of TDP-43 or FUS pathology utilizing immunohistochemical studies in autopsy material from 29 MSA patients. Results: TDP-43 pathology was generally rare, and there were no FUS lesions. The TDP-43 lesions were located predominantly in medio-temporal lobe and subcortical brain areas and were comprised mainly of dystrophic processes and perivascular (and subpial) lesions. Conclusions: The multisystem clinical symptoms and signs of MSA, and in particular the neurobehavioural/cognitive and pyramidal features, appear not to result from concomitant TDP-43 or FUS pathology, but rather from widespread white matter alpha-synuclein positive glial cytoplasmic inclusions and neurodegeneration in keeping with a primary alpha-synuclein-mediated oligodendrogliopathy. The gliodegenerative disease MSA evidently results from different pathogenetic mechanisms than neurodegenerative diseases linked to pathological TDP-43. C1 [Geser, F.; Malunda, J. A.; Lee, V. M. -Y.; Trojanowski, J. Q.] Univ Penn, Sch Med, HUP, Ctr Neurodegenerat Dis Res,Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Hurtig, H. I.; Duda, J. E.] Univ Penn, Sch Med, Penn Hosp, Dept Neurol, Philadelphia, PA 19104 USA. [Duda, J. E.] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Gilman, S.] Univ Michigan, Dept Neurol, Michigan Alzheimers Dis Res Ctr, Ann Arbor, MI USA. [Low, P. A.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Wenning, G. K.] Innsbruck Med Univ, Neurodegenerat Res Lab, Div Clin Neurobiol, Innsbruck, Austria. RP Trojanowski, JQ (reprint author), Univ Penn, Sch Med, HUP, Ctr Neurodegenerat Dis Res,Dept Pathol & Lab Med, Maloney 3rd Floor,36th & Spruce St, Philadelphia, PA 19104 USA. EM trojanow@mail.med.upenn.edu FU National Institutes of Health [AG-10124, AG-17586, NS044233, NS 32352, NS 44233, NS 22352, NS 43364]; Mayo CTSA [UL1 RR24150]; Mayo Funds; Federal Ministry of Education and Science, Vienna, Austria FX This work was funded by grants from the National Institutes of Health (AG-10124, AG-17586 and NS044233, NS 32352, NS 44233, NS 22352, NS 43364), Mayo CTSA (UL1 RR24150) and Mayo Funds. Dr Virginia M.-Y. Lee is the John H. Ware III Chair of Alzheimer's Research and Dr John Q. Trojanowski is the William Maul Measey-Truman G. Schnabel, Jr., MD Professor of Geriatric Medicine and Gerontology. Dr Sid Gilman is the William J. Herdman Distinguished University Professor of Neurology. Dr Gregor K. Wenning is Professor of Neurology and Clinical Neurobiology and he has received a Neuroscience Centre Grant by the Federal Ministry of Education and Science, Vienna, Austria. We thank the families of patients whose generosity made this research possible. We also thank Dr Manuela Neumann for providing us with the anti-phosporylated TDP-43 antibody (S409/410), John Robinson, BS, for the comments on the manuscript, and our colleagues at the Center for Neurodegenerative Disease Research and Department of Psychiatry, University of Pennsylvania School of Medicine, for their technical support and advice, particularly Theresa Schuck, BA, Lauren Stutzbach, BA, Michael Partain, BA and Mfon Umoh. NR 50 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD JUN PY 2011 VL 37 IS 4 BP 358 EP 365 DI 10.1111/j.1365-2990.2010.01136.x PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 763WA UT WOS:000290589200003 PM 20942898 ER PT J AU Woodby, LL Williams, BR Wittich, AR Burgio, KL AF Woodby, Lesa L. Williams, Beverly Rosa Wittich, Angelina R. Burgio, Kathryn L. TI Expanding the Notion of Researcher Distress: The Cumulative Effects of Coding SO QUALITATIVE HEALTH RESEARCH LA English DT Article DE coding; data collection and management; emotions / emotion work; end-of-life issues; research, qualitative; risk; stress / distress ID QUALITATIVE HEALTH RESEARCH; METHODOLOGICAL ISSUES; SENSITIVE TOPICS; LAST HOURS; LIFE; INTERVIEW; CANCER; CARE; REFLECTIONS; EXPLORATION AB Qualitative researchers who explore the individual's experience of health, illness, death, and dying often experience emotional stress in their work. In this article, we describe the emotional stress we experienced while coding semistructured, after-death interviews conducted with 38 next of kin of deceased veterans. Coding sensitive topic data required an unexpected level of emotional labor, the impact of which has not been addressed in the literature. In writing this discussion article, we stepped back from our roles as interviewers/coders and reflected on how our work affected us individually and as a team, and how a sequence of exposures could exert a cumulative effect for researchers in such a dual role. Through this article, we hope to generate an expanded discourse on how qualitative inquiry impacts the emotional well-being of researchers. C1 [Woodby, Lesa L.] Birmingham VA Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, Birmingham, AL 35233 USA. RP Woodby, LL (reprint author), Birmingham VA Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, GRECC 11G,700 S 19th St, Birmingham, AL 35233 USA. EM Lesa.Woodby@va.gov NR 72 TC 19 Z9 20 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7323 J9 QUAL HEALTH RES JI Qual. Health Res. PD JUN PY 2011 VL 21 IS 6 BP 830 EP 838 DI 10.1177/1049732311402095 PG 9 WC Information Science & Library Science; Social Sciences, Interdisciplinary; Social Sciences, Biomedical SC Information Science & Library Science; Social Sciences - Other Topics; Biomedical Social Sciences GA 759BH UT WOS:000290214400009 PM 21393618 ER PT J AU Deatrick, JA Given, B AF Deatrick, Janet A. Given, Barbara TI Creating a Pipeline for Tomorrow's Nurse Researchers SO RESEARCH IN NURSING & HEALTH LA English DT Editorial Material ID HIGH-SCHOOL-STUDENTS; EDUCATION; RETENTION; PROGRAM C1 [Deatrick, Janet A.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. [Given, Barbara] Michigan State Univ, Coll Nursing, E Lansing, MI 48824 USA. RP Deatrick, JA (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Room 223,Claire M Fagin Hall,418 Curie Blvd, Philadelphia, PA 19104 USA. NR 23 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD JUN PY 2011 VL 34 IS 3 BP 171 EP 175 DI 10.1002/nur.20436 PG 5 WC Nursing SC Nursing GA 762EG UT WOS:000290455000002 PM 21520145 ER PT J AU Simpson, T Rosenthal, C Gurrad, B Luterek, J Kaysen, D AF Simpson, Tracy Rosenthal, Christina Gurrad, Bethann Luterek, Jane Kaysen, Debra TI A PILOT STUDY EVALUATING MECHANISMS OF CHANGE AMONG PATIENTS WITH COMORBID PTSD AND ALCOHOL DEPENDENCE: METHODS AND FEASIBILITY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 [Simpson, Tracy; Rosenthal, Christina; Gurrad, Bethann; Luterek, Jane; Kaysen, Debra] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 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 JUN PY 2011 VL 35 IS 6 SU S BP 142A EP 142A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804301023 ER PT J AU Hata, S Fujishige, S Araki, Y Taniguchi, M Urakami, K Peskind, E Akatsu, H Araseki, M Yamamoto, K Martins, RN Maeda, M Nishimura, M Levey, A Chung, KA Montine, T Leverenz, J Fagan, A Goate, A Bateman, R Holtzman, DM Yamamoto, T Nakaya, T Gandy, S Suzuki, T AF Hata, Saori Fujishige, Sayaka Araki, Yoichi Taniguchi, Miyako Urakami, Katsuya Peskind, Elaine Akatsu, Hiroyasu Araseki, Masahiko Yamamoto, Kazuo Martins, Ralph N. Maeda, Masahiro Nishimura, Masaki Levey, Allan Chung, Kathryn A. Montine, Thomas Leverenz, James Fagan, Anne Goate, Alison Bateman, Randall Holtzman, David M. Yamamoto, Tohru Nakaya, Tadashi Gandy, Sam Suzuki, Toshiharu TI Alternative Processing of gamma-Secretase Substrates in Common Forms of Mild Cognitive Impairment and Alzheimer's Disease: Evidence for gamma-Secretase Dysfunction SO ANNALS OF NEUROLOGY LA English DT Article ID BETA-PROTEIN PRECURSOR; IN-VIVO; METABOLISM; CLEAVAGE; MEMBRANE; ALCADEIN; ENZYME; BRAIN; RATIO AB Objective: The most common pathogenesis for familial Alzheimer's disease (FAD) involves misprocessing (or alternative processing) of the amyloid precursor protein (APP) by gamma-secretase due to mutations of the presenilin 1 (PS1) gene. This misprocessing/alternative processing leads to an increase in the ratio of the level of a minor gamma-secretase reaction product (A beta 42) to that of the major reaction product (A beta 40). Although no PS1 mutations are present, altered A beta 42/40 ratios are also observed in sporadic Alzheimer's disease (SAD), and these altered ratios apparently reflect deposition of A beta 42 as amyloid. Methods: Using immunoprecipitation-mass spectrometry with quantitative accuracy, we analyzed in the cerebrospinal fluid (CSF) of various clinical populations the peptide products generated by processing of not only APP but also an unrelated protein, alcadein (Alc). Alc undergoes metabolism by the identical APP alpha-secretases and gamma-secretases, yielding a fragment that we have named p3-Alca because of the parallel genesis of p3-Alc(alpha) peptides and the p3 fragment of APP. As with A beta, both major and minor p3-Alc(alpha)s are generated. We studied the alternative processing of p3-Alc(alpha) in various clinical populations. Results: We previously reported that changes in the A beta 42/40 ratio showed covariance in a linear relationship with the levels of p3-Alc(alpha) [minor/major] ratio in media conditioned by cells expressing FAD-linked PS1 mutants. Here we studied the speciation of p3-Alc(alpha) in the CSF from 3 groups of human subjects (n 158): elderly nondemented control subjects; mild cognitive impairment (MCI) subjects with a clinical dementia rating (CDR) of 0.5; SAD subjects with CDR of 1.0; and other neurological disease (OND) control subjects. The CSF minor p3-Alc(alpha) variant, p3-Alc(alpha)38, was elevated (p < 0.05) in MCI subjects or SAD subjects, depending upon whether the data were pooled and analyzed as a single cohort or analyzed individually as 3 separate cohorts. Interpretation: These results suggest that some SAD may involve alternative processing of multiple c-secretase substrates, raising the possibility that the molecular pathogenesis of SAD might involve gamma-secretase dysfunction. ANN NEUROL 2011;69:1026-1031 C1 [Suzuki, Toshiharu] Hokkaido Univ, Neurosci Lab, Grad Sch Pharmaceut Sci, Dept Neurosci,Kita Ku, Sapporo, Hokkaido 0600812, Japan. [Taniguchi, Miyako; Urakami, Katsuya] Tottori Univ, Fac Med, Sch Hlth Sci, Dept Regulat Biol, Yonago, Tottori 683, Japan. [Peskind, Elaine] Univ Washington, Med Ctr, Dept Psychiat, Seattle, WA 98195 USA. [Peskind, Elaine] Univ Washington, Med Ctr, Alzheimers Dis Res Ctr, Seattle, WA 98195 USA. [Peskind, Elaine] VA Puget Sound Hlth Care Ctr, Seattle, WA USA. [Akatsu, Hiroyasu] Fukushimura Hosp, Choju Med Inst, Toyohashi, Aichi, Japan. [Yamamoto, Kazuo] Univ Tokyo, Dept Integrated Biosci, Grad Sch Frontier Sci, Kashiwa, Chiba, Japan. [Martins, Ralph N.] Edith Cowan Univ, Ctr Excellence Alzheimers Dis Res & Care, Joondalup, WA, Australia. [Martins, Ralph N.] Edith Cowan Univ, Sir James McCusker Alzheimers Dis Res Unit, Sch Exercise Biomed & Hlth Sci, Joondalup, WA, Australia. [Maeda, Masahiro] Immunobiol Labs Co Ltd IBL, Fujioka, Japan. [Nishimura, Masaki] Shiga Univ Med Sci, Neurol Unit, Mol Neurosci Res Ctr, Otsu, Shiga 52021, Japan. [Levey, Allan] Emory Univ, Dept Neurol, Emory Alzheimers Dis Res Ctr, Atlanta, GA 30322 USA. [Chung, Kathryn A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Montine, Thomas] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Fagan, Anne; Bateman, Randall; Holtzman, David M.] Washington Univ, Sch Med, Dept Neurol, Alzheimers Diseaase Reasrearch Ctr, St Louis, MO 63110 USA. [Gandy, Sam] Mt Sinai Sch Med, Dept Neurol, Alzheimers Dis Res Ctr, New York, NY USA. [Gandy, Sam] James J Peters Vet Adm Med Ctr, Bronx, NY USA. RP Suzuki, T (reprint author), Hokkaido Univ, Neurosci Lab, Grad Sch Pharmaceut Sci, Dept Neurosci,Kita Ku, Kita12,Nishi6, 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, Science, Culture, Sports, and Technology, Japan [20023001]; Washington University Alzheimer's Disease Research Center [P50 AG05681, P01AG03991]; University of Washington P50 Alzheimer's Disease Research Center; US Department of Veterans Affairs; Kurozumi Medical Foundation; Suzuken Memorial Foundation; National Institute on Aging [P01 AG10491, P50 AG005138]; Japan Society for the Promotion of Science (JSPS) FX This research was supported by a grant from the Ministry of Education, Science, Culture, Sports, and Technology, Japan (Grants-in-Aid for Scientific Research on Priority Areas 20023001 to T. S.).; We thank Patrick Hof, Brandon Wustman, Rosalie Crouch, and Yuhki Saito for helpful discussions. Some CSF samples from aged nondemented control subjects and from subjects suffering from various neurological diseases were provided by the Washington University Biomarkers Core, which is supported by the Washington University Alzheimer's Disease Research Center grant P50 AG05681 and P01AG03991. Some CSF samples were provided by the Washington University Resource Bank, which is supported by P50 AG05681 and P01 AG03991, and the University of Washington Resource Bank, which is supported by the University of Washington P50 Alzheimer's Disease Research Center and the US Department of Veterans Affairs. Some samples were also contributed by the Tottori University School of Health Sciences.; T. S. and T.N. are supported by Kurozumi Medical Foundation and Suzuken Memorial Foundation. S. G. is supported by National Institute on Aging grants P01 AG10491 and P50 AG005138. Authors S. H., Y.A., and M. A. are the recipients of research fellowships from the Japan Society for the Promotion of Science (JSPS) for young scientists. The other authors report no conflicts of interest. NR 17 TC 20 Z9 21 U1 0 U2 2 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 JUN PY 2011 VL 69 IS 6 BP 1026 EP 1031 DI 10.1002/ana.22343 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 782JA UT WOS:000292003100015 PM 21681798 ER PT J AU Goldman, RL Borckardt, JJ Frohman, HA O'Neil, PM Madan, A Campbell, LK Budak, A George, MS AF Goldman, Rachel L. Borckardt, Jeffrey J. Frohman, Heather A. O'Neil, Patrick M. Madan, Alok Campbell, Laura K. Budak, Amanda George, Mark S. TI Prefrontal cortex transcranial direct current stimulation (tDCS) temporarily reduces food cravings and increases the self-reported ability to resist food in adults with frequent food craving SO APPETITE LA English DT Article DE Transcranial direct current stimulation; tDCS; Brain stimulation; Food cravings; Obesity; Binge eating ID REAL-TIME FMRI; DRUG-ADDICTION; DOUBLE-BLIND; BRAIN-STIMULATION; EATING-DISORDERS; OBESITY; ACTIVATION; INVOLVEMENT; MODULATION; PREVENTION AB This study examined whether a 20-min session of prefrontal transcranial direct current stimulation (tDCS) (anode over the right prefrontal cortex and cathode over the left prefrontal cortex) would reduce food cravings and increase the self-reported ability to resist foods in 19 healthy individuals who reported frequent food cravings. Participants viewed computerized images of food and used computerized visual analogue scales to rate food cravings and inability to resist foods before, during, and after receiving either real or sham tDCS. This study employed a randomized within-subject crossover design; participants received both real and sham tDCS and were blind to the condition. Food cravings ratings were reduced in both conditions, however, the percent change in cravings ratings from pre- to post-stimulation was significantly greater for real stimulation than for sham. The percent change in inability to resist food from pre- to post-stimulation also showed a greater decrease in the real condition than for sham. Post hoc analyses suggest that active prefrontal tDCS acutely and significantly decreased food cravings ratings for sweet foods and carbohydrates more so than sham tDCS. No significant differences were seen in the amount of food ingested between real and sham tDCS. These findings in healthy subjects indicate that tDCS is able to temporarily reduce food cravings and improve the self-reported ability to resist foods. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Goldman, Rachel L.; Borckardt, Jeffrey J.; O'Neil, Patrick M.; Madan, Alok; Campbell, Laura K.; Budak, Amanda; George, Mark S.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Borckardt, Jeffrey J.; Frohman, Heather A.] Med Univ S Carolina, Dept Anesthesiol & Perioperat Med, Charleston, SC 29425 USA. [George, Mark S.] Med Univ S Carolina, Dept Neurol & Radiol, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Goldman, RL (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 1 South,67 President St, Charleston, SC 29425 USA. EM goldman@musc.edu OI Goldman, Rachel/0000-0001-6147-3934; Frohman, Heather/0000-0001-5199-7654 FU Covidien through the Obesity Society; National Institute for Neurological Disorders and Stroke at NIH; Cyberonics Inc.; Neurosciences Institute at MUSC; National Institute for Nursing Research; American Society for Gastrointestinal Endoscopy; Arena Pharmaceuticals; Merck Inc.; Orexigen Therapeutics; Weight Watchers International; Robert Wood Johnson Foundation; Center for Health Disparities Research at MUSC; NIH/NINR; Ocera Therapeutics, Inc.; Glaxo-Smith Kline; Jazz Pharmaceuticals; Brainsway; Cephos; Force Protection; NIH; DOD FX Dr. Goldman receives research funding from Covidien through the Obesity Society, Dr. Borckardt receives research funding from the National Institute for Neurological Disorders and Stroke at NIH, Cyberonics Inc., the Neurosciences Institute at MUSC, the National Institute for Nursing Research, the American Society for Gastrointestinal Endoscopy, and Covidien through the Obesity Society. Dr. Borckardt is also Consultant for TIF Management, LLC. Dr. O'Neil receives research funding from Arena Pharmaceuticals, Merck Inc., Orexigen Therapeutics and Weight Watchers International, and currently or recently has served as a consultant for Orexigen Therapeutics, Merck Inc., and Vivus. Dr. Madan receives research funding from the American Society for Gastrointestinal Endoscopy, Covidien through the Obesity Society, the Robert Wood Johnson Foundation, the Center for Health Disparities Research at MUSC, NIH/NINR, and Ocera Therapeutics, Inc. Dr. George reports research grants in the past 5 years from Glaxo-Smith Kline, Jazz Pharmaceuticals, Brainsway, Cephos, and Force Protection as well as the NIH and DOD. He has been an unpaid advisor to Brainsonix, Brainsway, Neuronetics, Neostim and Neosync (as they make products related to TMS), and a paid advisor to Jazz, Cyberonics, Neuropace, and Puretech ventures. The full amount of his advisory income has never been more than 10% of his university salary. MUSC has 2 patent applications in Dr. George's name on combining TMS with MRI. He has no equity investment in any device or pharmaceutical company. NR 48 TC 46 Z9 47 U1 4 U2 20 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-6663 EI 1095-8304 J9 APPETITE JI Appetite PD JUN PY 2011 VL 56 IS 3 BP 741 EP 746 DI 10.1016/j.appet.2011.02.013 PG 6 WC Behavioral Sciences; Nutrition & Dietetics SC Behavioral Sciences; Nutrition & Dietetics GA 781EF UT WOS:000291912700028 PM 21352881 ER PT J AU Rodrigues, GR Walker, RH Bader, B Danek, A Brice, A Cazeneuve, C Russaouen, O Lopes-Cendess, I Marques, W Tumas, V AF Rodrigues, Guilherme Riccioppo Walker, Ruth H. Bader, Benedikt Danek, Adrian Brice, Alexis Cazeneuve, Cecile Russaouen, Odile Lopes-Cendess, Iscia Marques, Wilson, Jr. Tumas, Vitor TI Clinical and genetic analysis of 29 Brazilian patients with Huntington's disease-like phenotype SO ARQUIVOS DE NEURO-PSIQUIATRIA LA English DT Article DE Huntington's disease; Huntington's disease-like; chorea-acanthocytosis; Huntington's disease-like 2 ID TRINUCLEOTIDE REPEAT EXPANSIONS; SPINOCEREBELLAR ATAXIA; CHOREA-ACANTHOCYTOSIS; CAG EXPANSION; PHENOCOPIES; HUNTINGTON-DISEASE-LIKE-2; JUNCTOPHILIN-3; ATROPHY AB Huntington's disease (HD) is a neurodegenerative disorder characterized by chorea, behavioral disturbances and dementia, caused by a pathological expansion of the CAG trinucleotide in the HTT gene. Several patients have been recognized with the typical HD phenotype without the expected mutation. The objective of this study was to assess the occurrence of diseases such as Huntington's disease-like 2 (HDL2), spinocerebellar ataxia (SCA) 1, SCA2, SCA3, SCA7, dentatorubral-pallidoluysian atrophy (DRPLA) and choreaacanthocytosis (ChAc) among 29 Brazilian patients with a HD-like phenotype. In the group analyzed, we found 3 patients with HDL2 and 2 patients with ChAc. The diagnosis was not reached in 79.3% of the patients. HDL2 was the main cause of the HD-like phenotype in the group analyzed, and is attributable to the African ancestry of this population. However, the etiology of the disease remains undetermined in the majority of the HD negative patients with HD-like phenotype. C1 [Rodrigues, Guilherme Riccioppo; Marques, Wilson, Jr.; Tumas, Vitor] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Neurosci & Behav Sci, BR-14049900 Ribeirao Preto, SP, Brazil. [Walker, Ruth H.] Mt Sinai Sch Med, New York, NY USA. [Walker, Ruth H.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA. [Bader, Benedikt; Danek, Adrian] Univ Munich, Dept Neurol, D-8000 Munich, Germany. [Brice, Alexis; Cazeneuve, Cecile; Russaouen, Odile] Hosp Pitie Salpetriere, AP HP, Neurogenet Unit, Dept Genet & Cytogenet, Paris, France. [Lopes-Cendess, Iscia] Univ Estadual Campinas, Sch Med Sci, Dept Med Genet, Campinas, SP, Brazil. RP Tumas, V (reprint author), Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Neurosci & Behav Sci, Campus Univ, BR-14049900 Ribeirao Preto, SP, Brazil. EM tumasv@rnp.fmrp.usp.br RI Danek, Adrian/G-7339-2011; Marques, Wilson/G-4240-2012; Tumas, Vitor/C-9949-2014 OI Danek, Adrian/0000-0001-8857-5383; Marques, Wilson/0000-0002-4589-2749; FU Bayerische Forschungsstiftung; German Federal Ministry of Research; Manchner Universitatsgesellschaft; Deutsch-Franzosische Hochschulstiftung; Advocacy for Neuroacanthocytosis Patients FX Dr. Danek serves on the editorial board of Zeitschrift fur Gerontoneurologie and Translational Neuroscience; has received speaker honoraria from Merz, Pfizer, Novartis, Janssen-Cilag and Neuro-Update; receives research support as Principal Investigator from Bayerische Forschungsstiftung, German Federal Ministry of Research, Manchner Universitatsgesellschaft, Deutsch-Franzosische Hochschulstiftung, and Advocacy for Neuroacanthocytosis Patients; and has served as an expert witness for German courts of justice in medicolegal cases NR 29 TC 7 Z9 7 U1 0 U2 5 PU ASSOC ARQUIVOS NEURO- PSIQUIATRIA PI SAO PAULO SP PA PR AMADEU AMARAL 47/33, 01327-010 SAO PAULO SP, BRAZIL SN 0004-282X J9 ARQ NEURO-PSIQUIAT JI Arq. Neuro-Psiquiatr. PD JUN PY 2011 VL 69 IS 3 BP 419 EP 423 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 783WR UT WOS:000292115600002 PM 21755114 ER PT J AU Helfand, M Tunis, S Whitlock, EP Pauker, SG Basu, A Chilingerian, J Harrell, FE Meltzer, DO Montori, VM Shepard, DS Kent, DM AF Helfand, Mark Tunis, Sean Whitlock, Evelyn P. Pauker, Stephen G. Basu, Anirban Chilingerian, Jon Harrell, Frank E., Jr. Meltzer, David O. Montori, Victor M. Shepard, Donald S. Kent, David M. CA Natl CTSA Strategic Goal Comm Comp TI A CTSA Agenda to Advance Methods for Comparative Effectiveness Research SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article DE patient-centered outcomes research; translational science; comparative effectiveness; clinical research methods ID HEALTH TECHNOLOGY-ASSESSMENT; DECISION-MAKING; INDIVIDUAL PATIENTS; CITIZENS JURIES; CLINICAL-TRIALS; PARTICIPATORY RESEARCH; RESEARCH PRIORITIES; SYSTEMATIC REVIEWS; COST-EFFECTIVENESS; RANDOMIZED TRIALS AB Clinical research needs to be more useful to patients, clinicians, and other decision makers. To meet this need, more research should focus on patient-centered outcomes, compare viable alternatives, and be responsive to individual patients' preferences, needs, pathobiology, settings, and values. These features, which make comparative effectiveness research (CER) fundamentally patient-centered, challenge researchers to adopt or develop methods that improve the timeliness, relevance, and practical application of clinical studies. In this paper, we describe 10 priority areas that address 3 critical needs for research on patient-centered outcomes (PCOR): (1) developing and testing trustworthy methods to identify and prioritize important questions for research; (2) improving the design, conduct, and analysis of clinical research studies; and (3) linking the process and outcomes of actual practice to priorities for research on patient-centered outcomes. We argue that the National Institutes of Health, through its clinical and translational research program, should accelerate the development and refinement of methods for CER by linking a program of methods research to the broader portfolio of large, prospective clinical and health system studies it supports. Insights generated by this work should be of enormous value to PCORI and to the broad range of organizations that will be funding and implementing CER. Clin Trans Sci 2011; Volume 4: 188-198 C1 [Helfand, Mark] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Ctr, Portland, OR 97201 USA. [Helfand, Mark] Portland VA Med Ctr, Dept Hosp & Specialty Med, Portland, OR USA. [Tunis, Sean] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. [Tunis, Sean] Ctr Med Technol Policy, Baltimore, MD USA. [Tunis, Sean] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Tunis, Sean] Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA USA. [Tunis, Sean] Stanford Univ, Ctr Hlth Policy, Stanford, CA 94305 USA. [Whitlock, Evelyn P.] Kaiser Permanente Ctr Hlth Res, Ctr Hlth Res, Portland, OR USA. [Whitlock, Evelyn P.] Oregon Hlth & Sci Univ, Oregon Evidence Based Practice Ctr, Portland, OR 97201 USA. [Pauker, Stephen G.] Tufts Med Ctr, Tufts Clin & Translat Sci Inst, Boston, MA USA. [Pauker, Stephen G.] Tufts Med Ctr, Dept Med, Inst Clin Res & Hlth Policy Studies, Div Clin Decis Making Informat & Telemed, Boston, MA USA. [Basu, Anirban] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Basu, Anirban] Univ Washington, Dept Pharm, Seattle, WA 98195 USA. [Basu, Anirban] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Chilingerian, Jon] Brandeis Univ, Heller Sch, Sch Social Policy & Management, Waltham, MA 02254 USA. [Harrell, Frank E., Jr.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. [Meltzer, David O.] Univ Chicago, Ctr Hlth & Social Sci, Chicago, IL 60637 USA. [Meltzer, David O.] Univ Chicago, Hosp Med, Chicago, IL 60637 USA. [Montori, Victor M.] Mayo Clin, Healthcare Delivery Res Program, Translating CER Core, Mayo CTSA, Rochester, MN USA. [Montori, Victor M.] Mayo Clin, Dept Hlth Sci Res, Div Healthcare & Policy Res, Rochester, MN USA. [Shepard, Donald S.] Brandeis Univ, Heller Sch, Schneider Inst Hlth Policy, Waltham, MA 02254 USA. [Kent, David M.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Dept Med, Tufts Clin & Translat Sci Inst, Boston, MA USA. RP Helfand, M (reprint author), Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Ctr, Portland, OR 97201 USA. EM helfand@ohsu.edu RI Meltzer, David/C-2926-2009 OI Meltzer, David/0000-0003-2790-7393; Montori, Victor/0000-0003-0595-2898 FU National Center for Research Resources, NIH, through the CTSA, a trademark of DHHS, part of the Roadmap Initiative FX This project has been funded in whole or in part with Federal funds from the National Center for Research Resources, NIH, through the CTSA, a trademark of DHHS, part of the Roadmap Initiative, "Re-Engineering the Clinical Research Enterprise." The manuscript was approved by the CTSA Consortium Publications Committee. NR 78 TC 25 Z9 25 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD JUN PY 2011 VL 4 IS 3 BP 188 EP 198 DI 10.1111/j.1752-8062.2011.00282.x PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 783TR UT WOS:000292107400014 PM 21707950 ER PT J AU Barragan, VA Mejia, ME Travez, A Zapata, S Hartskeerl, RA Haake, DA Trueba, GA AF Barragan, Veronica A. Eugenia Mejia, Maria Travez, Andres Zapata, Sonia Hartskeerl, Rudy A. Haake, David A. Trueba, Gabriel A. TI Interactions of Leptospira with Environmental Bacteria from Surface Water SO CURRENT MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; 16S RIBOSOMAL-RNA; PATHOGENIC LEPTOSPIRA; GENUS LEPTOSPIRA; GENOME SEQUENCE; FRESH-WATER; SPIROCHETE; OUTBREAK; GRADIENT; SURVIVAL AB Leptospires can persist for months in nutrient-poor aqueous environments prior to transmission to a mammalian host. Interactions with environmental bacteria and biofilm formation are possible mechanisms of persistence of leptospires in the environment. Bacteria isolated from rivers in the Ecuadorian rainforest were tested for their ability to support leptospiral viability. We found that co-culture with Sphingomonas spp., but not Flavobacterium spp. or Delftia spp., enabled survival of L. biflexa and L. meyeri for up to a year in distilled water. We also found that L. interrogans biofilms formed in distilled water contained viable organisms that rapidly dispersed into the planktonic phase in the presence of nutrients in serum or EMJH medium. These data inform our understanding of leptospiral survival strategies that enable long-term persistence in nutrient-poor conditions yet allow rapid mobilization when nutrients become available. C1 [Barragan, Veronica A.; Eugenia Mejia, Maria; Travez, Andres; Zapata, Sonia; Trueba, Gabriel A.] Univ San Francisco Quito, Inst Microbiol, Quito, Ecuador. [Haake, David A.] VA Greater Los Angeles Healthcare Syst GLA, Los Angeles, CA USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Hartskeerl, Rudy A.] Royal Trop Inst KIT, WHO FAO OIE, Amsterdam, Netherlands. [Hartskeerl, Rudy A.] Royal Trop Inst KIT, Natl Collaborating Ctr Reference & Res Leptospiro, Dept Biomed Res, Amsterdam, Netherlands. RP Barragan, VA (reprint author), Univ San Francisco Quito, Inst Microbiol, Diego Robles & Via Interocean,POB 17-1200-841, Quito, Ecuador. EM vbarragan@usfq.edu.ec OI Trueba, Gabriel/0000-0003-2617-9021 NR 36 TC 14 Z9 14 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD JUN PY 2011 VL 62 IS 6 BP 1802 EP 1806 DI 10.1007/s00284-011-9931-3 PG 5 WC Microbiology SC Microbiology GA 790AO UT WOS:000292561100022 PM 21479795 ER PT J AU Swenson, ER AF Swenson, Erik R. TI Con: Rebuttal SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Editorial Material ID ALTITUDE PULMONARY-EDEMA; RECREATIONAL CLIMBERS; LUNG; MODULATION; BARRIER; HYPOXIA; FLUID C1 Univ Washington, Med Serv, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Swenson, ER (reprint author), Univ Washington, Med Serv, VA Puget Sound Hlth Care Syst, S-111 PULM,1660 S Columbian Way, Seattle, WA 98108 USA. EM eswenson@u.washington.edu NR 13 TC 2 Z9 2 U1 2 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1527-0297 J9 HIGH ALT MED BIOL JI High Alt. Med. Biol. PD SUM PY 2011 VL 12 IS 2 BP 131 EP 132 DI 10.1089/ham.2011.1010 PG 2 WC Biophysics; Public, Environmental & Occupational Health; Sport Sciences SC Biophysics; Public, Environmental & Occupational Health; Sport Sciences GA 786EJ UT WOS:000292285800006 PM 21718160 ER PT J AU Smith, DE Johnson, JL Harrington, T Kitchen, L Albertson, L Lane, E AF Smith, Denise E. Johnson, Jennifer L. Harrington, Tim Kitchen, Linda Albertson, LaVonne Lane, Ellen TI POST PACU CLIENT SURVEY SO JOURNAL OF PERIANESTHESIA NURSING LA English DT Meeting Abstract C1 [Smith, Denise E.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1089-9472 J9 J PERIANESTH NURS JI J. PeriAnesthesia Nurs. PD JUN PY 2011 VL 26 IS 3 BP 196 EP 196 PG 1 WC Nursing SC Nursing GA 781DS UT WOS:000291911400054 ER PT J AU Livhits, M Gibbons, MM de Virgilio, C O'Connell, JB Leonardi, MJ Ko, CY Zingmond, DS AF Livhits, Masha Gibbons, Melinda Maggard de Virgilio, Christian O'Connell, Jessica B. Leonardi, Michael J. Ko, Clifford Y. Zingmond, David S. TI Coronary Revascularization after Myocardial Infarction Can Reduce Risks of Noncardiac Surgery SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID PERIOPERATIVE CARDIOVASCULAR EVALUATION; MAJOR VASCULAR-SURGERY; CARDIAC RISK; ARTERY DISEASE; INDEX; INTERVENTION; ANGIOPLASTY; OPERATIONS; OUTCOMES AB BACKGROUND: Recent studies suggest that preoperative coronary revascularization overall does not improve outcomes after noncardiac surgery. It is not known whether this holds true for high-risk patients with a history of recent MI. Our objective was to determine whether preoperative revascularization improves outcomes after noncardiac surgery in patients with a recent MI. STUDY DESIGN: Using the California Patient Discharge Database, we retrospectively analyzed patients with a recent MI who underwent hip surgery, cholecystectomy, bowel resection, elective abdominal aortic aneurysm repair, and lower extremity amputation from 1999 to 2004 (n = 16,478). Postoperative 30-day reinfarction and 30-day and 1-year mortality were compared for patients who underwent preoperative revascularization (percutaneous transluminal coronary angioplasty, coronary stenting, or coronary artery bypass graft) and those who were not revascularized using univariate analyses and multivariate logistic regression. Relative risks with 95% confidence intervals were estimated using bootstrapping with 1,000 repetitions. RESULTS: Patients with a recent MI who were revascularized before surgery had an approximately 50% decreased rate of reinfarction (5.1% versus 10.0%; p < 0.001) and 30-day (5.2% versus 11.3%; p < 0.001) and 1-year mortality (18.3% versus 35.8%; p < 0.001) compared with those who were not. Stenting within 1 month of surgery was associated with a trend toward increased reinfarction (relative risk: 1.36; 95% CI, 0.96-1.97), and coronary artery bypass graft was associated with a decreased risk (relative risk: 0.70; 95% CI, 0.55-0.95). CONCLUSIONS: This large sample representing real world practice suggests that patients with a recent MI can benefit from preoperative revascularization. Coronary artery bypass graft can improve outcomes more than stenting, especially when surgery is necessary within 1 month of revascularization, but additional prospective studies are indicated. (J Am Coll Surg 2011; 212: 1018-1026. (C) 2011 by the American College of Surgeons) C1 [Livhits, Masha; Gibbons, Melinda Maggard; O'Connell, Jessica B.; Leonardi, Michael J.; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Livhits, Masha; Gibbons, Melinda Maggard; O'Connell, Jessica B.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Zingmond, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Gibbons, Melinda Maggard] OliveView UCLA, Dept Surg, Sylmar, CA USA. [de Virgilio, Christian] Harbor UCLA Med Ctr, Dept Surg, Torrance, CA 90509 USA. [de Virgilio, Christian] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. RP Livhits, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 LeConte Ave,72-215 CHS, Los Angeles, CA 90095 USA. EM mlivhits@mednet.ucla.edu FU VA Department of Surgery; Robert Wood Johnson Physician Faculty; NIA [1K08AG023024] FX The VA Department of Surgery provided support for Drs Livhits and Gibbons. Dr Gibbons' time was supported in part by a grant from the Robert Wood Johnson Physician Faculty Scholars program. Dr Zingmond was supported by an NIA Mentored Clinical Scientist Award (1K08AG023024). NR 24 TC 12 Z9 12 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2011 VL 212 IS 6 BP 1018 EP 1026 DI 10.1016/j.jamcollsurg.2011.02.018 PG 9 WC Surgery SC Surgery GA 782BD UT WOS:000291981600014 PM 21441043 ER PT J AU Ingraham, AM Cohen, ME Raval, MV Ko, CY Nathens, AB AF Ingraham, Angela M. Cohen, Mark E. Raval, Mehul V. Ko, Clifford Y. Nathens, Avery B. TI Variation in Quality of Care after Emergency General Surgery Procedures in the Elderly SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SURGICAL OUTCOMES; GASTRIC-CANCER; UNITED-STATES; RISK; POPULATION; MORTALITY; IMPACT; AGE; ESOPHAGUS; CARCINOMA AB BACKGROUND: The elderly (age >= 65 years) comprise an increasing proportion of patients undergoing emergency general surgery (EGS) procedures and have distinct needs compared with the young. We postulated that the needs of the elderly require different processes of care than those required for the young to assure optimal outcomes. To explore this hypothesis, we evaluated 30-day outcomes following EGS procedures in the young and the elderly and determined whether hospital performance was consistent across these 2 age strata. STUDY DESIGN: With data from the American College of Surgeons National Surgical Quality Improvement Program (2005 to 2008), regression models were constructed for serious morbidity and mortality for all patients undergoing EGS procedures and separately for young and elderly patients. These models allowed for estimation of the risk of adverse outcomes associated with advanced age and the generation of hospital-level observed to expected (O/E) ratios. We evaluated the correlation between hospital O/Eratios for the young and the elderly and the concordance of outlier status (hospitals with CIs of O/E ratios excluding 1) with weighted kappa across these 2 age groups. RESULTS: Among 68,003 procedures at 186 hospitals, elderly patients had a higher crude and adjusted risk for serious morbidity (27.9% versus 9.7%, p < 0.0001; odds ratio 1.17,95% CI 1.10 to 1.24) and mortality (15.2% versus 2.5%, p < 0.0001; odds ratio 2.29, 95% CI 2.09 to 2.51). When outcomes for elderly versus younger patients were compared, there was fair to moderate agreement on hospital performance for serious morbidity (r = 0.43; kappa = 0.30) but not for mortality (r = 0.10; kappa = 0.17). CONCLUSIONS: Elderly patients are at substantially greater risk for adverse events following EGS procedures. Hospitals had only slight agreement in mortality outcomes in the elderly compared with those in young patients. Processes of care that may account for this disparity should be further investigated. (J Am Coll Surg 2011;212:1039-1048. (C) 2011 by the American College of Surgeons) C1 [Ingraham, Angela M.] Univ Cincinnati, Dept Surg, Coll Med, Cincinnati, OH 45267 USA. [Ingraham, Angela M.; Cohen, Mark E.; Raval, Mehul V.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Raval, Mehul V.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Nathens, Avery B.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Div Surg & Trauma, Toronto, ON M5B 1W8, Canada. RP Ingraham, AM (reprint author), Univ Cincinnati, Dept Surg, Coll Med, ML 0558,231 Albert Sabin Way,Room 1586, Cincinnati, OH 45267 USA. EM aingraham@facs.org OI Raval, Mehul/0000-0002-1527-2661 FU American College of Surgeons; John Gray Research Fellowship; Daniel F and Ada L Rice Foundation; Canada Research Chair in Systems of Trauma Care FX Drs Ingraham and Raval are supported by the Clinical Scholar in Residence Program at the American College of Surgeons. Dr Raval is also supported by the John Gray Research Fellowship and the Daniel F and Ada L Rice Foundation. Dr Nathens is supported by a Canada Research Chair in Systems of Trauma Care. NR 35 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2011 VL 212 IS 6 BP 1039 EP 1048 DI 10.1016/j.jamcollsurg.2011.03.001 PG 10 WC Surgery SC Surgery GA 782BD UT WOS:000291981600017 PM 21620289 ER PT J AU Lawson, EH Wang, X Cohen, ME Hall, BL Tanzman, H Ko, CY AF Lawson, Elise H. Wang, Xue Cohen, Mark E. Hall, Bruce Lee Tanzman, Howard Ko, Clifford Y. TI Morbidity and Mortality after Colorectal Procedures: Comparison of Data from the American College of Surgeons Case Log System and the ACS NSQIP SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SURGICAL QUALITY IMPROVEMENT; DATABASES AB BACKGROUND: Improving the quality of surgical care depends upon collection of robust data. The American College of Surgeons Case Log System enables surgeons to self-report patient risk factors and outcomes. In contrast, the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) uses trained data abstractors to record similar data and uses a strict data collection methodology. The objective of this study was to assess bias in data entry for colorectal cases by comparing data in these 2 registries. STUDY DESIGN: One year of NSQIP (July 1, 2008 to June 30, 2009) and 7 years of Case Log (2003 to 2010) data were examined. Colorectal cases were identified by current procedural terminology code. The frequencies of comparably defined variables were compared, and mortality models were developed using logistic regression. Observed and expected mortality rates were compared. RESULTS: Rates of most risk factor and outcome variables were significantly higher in NSQIP than those in Case Log. NSQIP had a higher unadjusted mortality rate (4.46% versus 3.69%, p < 0.001); however, the adjusted odds of mortality was significantly higher in Case Log (odds ratio 1.32, p < 0.05). The Case Log model overpredicted mortality in NSQIP by 22%, whereas the NSQIP model underpredicted mortality in Case Log by 12%. CONCLUSIONS: Significant differences exist between risk factor and outcome data in NSQIP and Case Log for colorectal procedures. These differences demonstrate the need for standardized data collection methods, as is required by NSQIP, including use of standard definitions, adherence to a follow-up period for outcomes, and use of audits. These measures would improve the validity of using a self-reported database to evaluate and benchmark performance. (J Am Coll Surg 2011; 212:1077-1085. (C) 2011 by the American College of Surgeons) C1 [Lawson, Elise H.] Univ Calif Los Angeles, Med Ctr, Dept Surg, Los Angeles, CA 90095 USA. [Lawson, Elise H.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Wang, Xue; Cohen, Mark E.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Hall, Bruce Lee] John Cochran Vet Affairs Med Ctr, Dept Surg, St Louis, MO USA. [Hall, Bruce Lee] Washington Univ, Sch Med, St Louis, MO USA. [Hall, Bruce Lee] Barnes Jewish Hosp, St Louis, MO 63110 USA. RP Lawson, EH (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Surg, CHS 72-215,10833 LeConte Ave, Los Angeles, CA 90095 USA. EM elawson@mednet.ucla.edu FU Robert Wood Johnson Foundation through the American College of Surgeons FX Dr Lawson was supported by the Robert Wood Johnson Foundation Clinical Scholars Program through the American College of Surgeons. NR 10 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2011 VL 212 IS 6 BP 1077 EP 1085 DI 10.1016/j.jamcollsurg.2011.03.002 PG 9 WC Surgery SC Surgery GA 782BD UT WOS:000291981600021 PM 21470879 ER PT J AU Hanlon, JT Wang, XG Handler, SM Weisbord, S Pugh, MJ Semla, T Stone, RA Aspinall, SL AF Hanlon, Joseph T. Wang, Xiaogiang Handler, Steven M. Weisbord, Steven Pugh, Mary Jo Semla, Todd Stone, Roslyn A. Aspinall, Sherrie L. TI Potentially Inappropriate Prescribing of Primarily Renally Cleared Medications for Older Veterans Affairs Nursing Home Patients SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY 12-15, 2010 CL Orlando, FL SP Amer Geriatr Soc ID CHRONIC KIDNEY-DISEASE; MINIMUM DATA SET; TERM-CARE FACILITIES; CREATININE CLEARANCE; COGNITIVE PERFORMANCE; ELDERLY-PATIENTS; DRUG; GUIDELINES; VALIDATION; FRAIL AB Background: Inappropriate prescribing of primarily renally cleared medications in older patients with kidney disease can lead to adverse outcomes. Objectives: To estimate the prevalence of potentially inappropriate prescribing of 21 primarily renally cleared medications based on 2 separate estimates of renal function and to identify factors associated with this form of suboptimal prescribing in older VA nursing home (NH) patients. Design: Longitudinal study Participants: Participants were 1304 patients, aged 65 years or older, admitted between January 1, 2004, and June 30, 2005, for 90 days or more to 1 of 133 VA NHs. Main Measures: Potentially inappropriate prescribing of primarily renally cleared medications determined by estimating creatinine clearance using the Cockcroft Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations and applying explicit guidelines for contraindicated medications and dosing. Key Results: The median estimated creatinine clearance via CG was 67 mL/min, whereas it was 80 mL/min/1.73m(2) with the MDRD. Overall, 11.89% patients via CG and only 5.98% via MDRD had evidence of potentially inappropriate prescribing of at least 1 renally cleared medication. The most commonly involved medications were ranitidine, glyburide, gabapentin, and nitrofurantoin. Factors associated with potentially inappropriate prescribing as per the CG were age older than 85 (adjusted odds ratio [AOR] 4.24, 95% confidence interval [CI] 2.42-7.43), obesity (AOR 0.26, 95% CI 0.14-0.50) and having multiple comorbidities (AOR 1.09 for each unit increase in the Charlson comorbidity index, 95% CI 1.01-1.19). Conclusions: Potentially inappropriate prescribing of renally cleared medications is common in older VA NH patients. Intervention studies to improve the prescribing of primarily renally cleared medications in nursing homes are needed. (J Am Med Dir Assoc 2011; 12: 377-383) C1 [Hanlon, Joseph T.; Handler, Steven M.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.; Aspinall, Sherrie L.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.; Handler, Steven M.] VAPHS, GRECC, Pittsburgh, PA USA. [Hanlon, Joseph T.; Wang, Xiaogiang; Handler, Steven M.; Weisbord, Steven; Stone, Roslyn A.; Aspinall, Sherrie L.] CHERP, Pittsburgh, PA USA. [Handler, Steven M.] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15213 USA. [Weisbord, Steven] Univ Pittsburgh, Sch Med, Renal Sect, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA. [Weisbord, Steven] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Pugh, Mary Jo] Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. [Semla, Todd; Aspinall, Sherrie L.] US Dept Vet Affairs, VA Pharm Benefits Management Serv, Hines, IL USA. [Semla, Todd] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Semla, Todd] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL USA. [Stone, Roslyn A.] Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. RP Hanlon, JT (reprint author), Univ Pittsburgh, Dept Med Geriatr, Kaufman Med Bldg,Suite 514,3471 5th Ave, Pittsburgh, PA 15213 USA. EM jth14@pitt.edu OI Handler, Steven/0000-0002-3940-3224; Pugh, Mary Jo/0000-0003-4196-7763 FU AHRQ HHS [R01 HS017695]; NCRR NIH HHS [K12 RR023267]; NIA NIH HHS [R56 AG027017-04, K07 AG033174, K07 AG033174-01A1, K07 AG033174-02, K07 AG033174-03, K07AG033174, P30 AG024827, P30AG024827, R01 AG027017, R01 AG034056, R01 AG034056-01, R01 AG034056-02, R01AG027017, R01AG034056, R56 AG027017, T32 AG021885]; NIMH NIH HHS [R34 MH082682]; NINR NIH HHS [R01 NR010135] NR 39 TC 24 Z9 24 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD JUN PY 2011 VL 12 IS 5 BP 377 EP 383 DI 10.1016/j.jamda.2010.04.008 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 783DI UT WOS:000292061300010 PM 21450179 ER PT J AU Pantaleo, MA Astolfi, A Indio, V Moore, R Thiessen, N Heinrich, MC Gnocchi, C Santini, D Catena, F Formica, S Martelli, PL Casadio, R Pession, A Biasco, G AF Pantaleo, Maria A. Astolfi, Annalisa Indio, Valentina Moore, Richard Thiessen, Nina Heinrich, Michael C. Gnocchi, Chiara Santini, Donatella Catena, Fausto Formica, Serena Martelli, Pier Luigi Casadio, Rita Pession, Andrea Biasco, Guido TI SDHA Loss-of-Function Mutations in KIT-PDGFRA Wild-Type Gastrointestinal Stromal Tumors Identified by Massively Parallel Sequencing SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CARNEY-STRATAKIS-SYNDROME; SUCCINATE-DEHYDROGENASE; THERAPEUTIC TARGET; MOLECULAR-GENETICS; IMATINIB; EXPRESSION; PARAGANGLIOMA; DISEASE AB Approximately 10%-15% of gastrointestinal stromal tumors (GISTs) in adults do not harbor any mutation in the KIT or PDGFRA genes (ie, KIT/PDGFRA wild-type GISTs). Recently, mutations in SDHB and SDHC (which encode succinate dehydrogenase subunits B and C, respectively) but not in SDHA and SDHD (which encode subunits A and D, respectively) were identified in KIT/PDGFRA wild-type GISTs. To search for novel pathogenic mutations, we sequenced the tumor transcriptome of two young adult patients who developed sporadic KIT/PDGFRA wild-type GISTs by using a massively parallel sequencing approach. The only variants identified as disease related by computational analysis were in SDHA. One patient carried the homozygous nonsense mutation p.Ser384X, the other patient was a compound heterozygote harboring a p.Arg31X nonsense mutation and a p.Arg589Trp missense mutation. The heterozygous nonsense mutations in both patients were present in germline DNA isolated from peripheral blood. Protein structure analysis indicates that all three mutations lead to functional inactivation of the protein. This is the first report, to our knowledge, that identifies SDHA inactivation as a common oncogenic event in GISTs that lack a mutation in KIT and PDGFRA. C1 [Pantaleo, Maria A.; Biasco, Guido] Univ Bologna, Dept Hematol & Oncol Sci L&A Seragnoli, St Orsola Malpighi Hosp, I-40138 Bologna, Italy. [Santini, Donatella] Univ Bologna, Pathol Unit, St Orsola Malpighi Hosp, I-40138 Bologna, Italy. [Catena, Fausto] Univ Bologna, Dept Surg & Transplantat, St Orsola Malpighi Hosp, I-40138 Bologna, Italy. [Pantaleo, Maria A.; Astolfi, Annalisa; Indio, Valentina; Formica, Serena; Pession, Andrea; Biasco, Guido] Univ Bologna, Giorgio Prodi Canc Res Ctr, I-40138 Bologna, Italy. [Indio, Valentina; Martelli, Pier Luigi; Casadio, Rita] Univ Bologna, Biocomp Grp, Dept Biol, I-40138 Bologna, Italy. [Moore, Richard; Thiessen, Nina] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada. [Heinrich, Michael C.] Portland VA Med Ctr, Dept Med, Portland, OR USA. [Heinrich, Michael C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Gnocchi, Chiara] Novartis Oncol, Origgio, Italy. [Formica, Serena; Pession, Andrea] Univ Bologna, Pediat Unit, Dept Gynecol Obstet & Pediat Sci, I-40138 Bologna, Italy. RP Pantaleo, MA (reprint author), Univ Bologna, Dept Hematol & Oncol Sci LA Seragnoli, St Orsola Malpighi Hosp, Via Massarenti 9, I-40138 Bologna, Italy. EM maria.pantaleo@unibo.it RI Indio, Valentina/G-1869-2011; Martelli, Pier Luigi/I-8824-2012; Casadio, Rita/K-4814-2015 OI Martelli, Pier Luigi/0000-0002-0274-5669; Casadio, Rita/0000-0002-7462-7039; PANTALEO, MARIA ABBONDANZA/0000-0002-0177-6957; astolfi, annalisa/0000-0002-2732-0747; Indio, Valentina/0000-0002-8854-3821 FU Novartis Oncology, Origgio, Italy; VA Merit Review grant; GIST Cancer Research Fund; Life Raft Group; Novartis Oncology FX Novartis Oncology, Origgio, Italy; VA Merit Review grant (to M.C.H.); GIST Cancer Research Fund (to M.C.H.); Life Raft Group (to M.C.H.); Novartis Oncology (to M.C.H.). NR 24 TC 70 Z9 72 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN PY 2011 VL 103 IS 12 BP 983 EP 987 DI 10.1093/jnci/djr130 PG 5 WC Oncology SC Oncology GA 784ZP UT WOS:000292197500012 PM 21505157 ER PT J AU Boyle, T Haney, J Lenhart, P Montoya, R Chesnut, P Merrick, D Camidge, RD Franklin, W AF Boyle, Theresa Haney, Jerry Lenhart, Patricia Montoya, Rosita Chesnut, Patrick Merrick, Daniel Camidge, Ross D. Franklin, Wilbur TI CORRELATION OF THYMIDYLATE SYNTHASE GENOTYPE AND PROTEIN EXPRESSION AND ASSOCIATION WITH LUNG CANCER SURVIVAL SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE thymidylate synthase; genotype; protein; NSCLC; polymorphism; VNTR C1 [Boyle, Theresa; Haney, Jerry; Lenhart, Patricia; Montoya, Rosita; Chesnut, Patrick; Camidge, Ross D.; Franklin, Wilbur] Univ Colorado Denver, Denver, CO USA. [Merrick, Daniel] Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU S BP S1084 EP S1085 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 779HX UT WOS:000291769800262 ER PT J AU Hudish, TM Opincariu, LI Mozer, AB Johnson, MS Cleaver, TG Malkoski, SP Merrick, DT Keith, RL AF Hudish, Tyler M. Opincariu, Laura I. Mozer, Anthony B. Johnson, Micah S. Cleaver, Timothy G. Malkoski, Stephen P. Merrick, Daniel T. Keith, Robert L. TI N-NITROSO-TRIS-CHLOROETHYLUREA INDUCES PRE-MALIGNANT SQUAMOUS DYSPLASIA IN MICE SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE NTCU; squamous cell carcinoma; Lung cancer; prostaglandin C1 [Keith, Robert L.] Denver VA Med Ctr, Div Pulm Sci & Crit Care Med, Denver, CO USA. [Cleaver, Timothy G.; Malkoski, Stephen P.] Univ Colorado Denver, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU S BP S1095 EP S1096 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 779HX UT WOS:000291769800276 ER PT J AU Merrick, DT Coldren, CD Franklin, W Sugita, M Miller, YE Keith, RL Kennedy, TC Chesnut, P Mascaux, C Hirsch, FR Geraci, MW Nemenoff, R AF Merrick, Daniel T. Coldren, Chris D. Franklin, Wilbur Sugita, Michio Miller, York E. Keith, Robert L. Kennedy, Timothy C. Chesnut, Patrick Mascaux, Celine Hirsch, Fred R. Geraci, Mark W. Nemenoff, Raphael TI IDENTIFICATION OF ALTERATIONS IN GENE EXPRESSION THAT DISTINGUISH PERSISTENT FROM REGRESSIVE BRONCHIAL DYSPLASIA SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Bronchial dysplasia; Persistence; gene expression C1 [Merrick, Daniel T.] Denver VAMC, Denver, CO USA. [Franklin, Wilbur; Miller, York E.; Keith, Robert L.; Kennedy, Timothy C.; Chesnut, Patrick; Mascaux, Celine; Hirsch, Fred R.; Geraci, Mark W.] Univ Colorado, Ctr Canc, Sch Med, Boulder, CO 80309 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU S BP S1097 EP S1098 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 779HX UT WOS:000291769800278 ER PT J AU Merrick, DT Bessessen, M Johnson, SC Clagett, TA Jackson, MK Keith, RL Byers, TE Feser, WJ Franklin, W Bunn, P Miller, YE AF Merrick, Daniel T. Bessessen, Mary Johnson, Steven C. Clagett, Thomas A. Jackson, Mary K. Keith, Robert L. Byers, Tim E. Feser, William J. Franklin, Wilbur Bunn, Paul Miller, York E. TI BRONCHIAL DYSPLASIA IS MORE FREQUENT AND MORE ATYPICAL IN BIOPSY AND SPUTUM MATERIAL FROM HIV INFECTED SUBJECTS: A PRELIMINARY REPORT FROM AN ONGOING STUDY SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE HIV infection; Sputum; bronchial biopsy; Bronchial dysplasia C1 [Merrick, Daniel T.; Bessessen, Mary] Denver VAMC, Denver, CO USA. [Bunn, Paul] Univ Colorado, Ctr Canc, Sch Med, Boulder, CO 80309 USA. [Keith, Robert L.; Miller, York E.] Vet Adm Med Ctr, Div Pulm Sci & Crit Care Med, Los Angeles, CA USA. [Feser, William J.] Colorado Sch Publ Hlth, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU S BP S1096 EP S1097 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 779HX UT WOS:000291769800277 ER PT J AU Miller, YE Blatchford, PJ Franklin, W Kennedy, TC Merrick, D Minna, JD Kelly, K Mao, J Massion, PP Wilson, DO Hirsch, FR Bunn, P Geraci, MW Kittelson, JK Keith, RL AF Miller, York E. Blatchford, Patrick J. Franklin, Wilbur Kennedy, Timothy C. Merrick, Daniel Minna, John D. Kelly, Karen Mao, Jenny Massion, Pierre P. Wilson, David O. Hirsch, Fred R. Bunn, Paul Geraci, Mark W. Kittelson, John K. Keith, Robert L. TI ILOPROST IMPROVES ENDOBRONCHIAL DYSPLASIA IN FORMER SMOKERS: IMPLICATIONS FOR PHASE II CHEMOPREVENTION TRIAL DESIGN SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE prostacyclin; chemoprevention; Lung cancer; premalignancy C1 [Miller, York E.; Keith, Robert L.] Vet Adm Med Ctr, Div Pulm Sci & Crit Care Med, Nashville, TN USA. [Franklin, Wilbur; Kennedy, Timothy C.; Hirsch, Fred R.; Kittelson, John K.] Univ Colorado Denver, Denver, CO 80202 USA. [Merrick, Daniel] Denver Vet Affairs Med Ctr, Denver, CO USA. [Minna, John D.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX USA. [Kelly, Karen] Uc Davis, Davis, CA USA. [Mao, Jenny] Univ New Mexico, Albuquerque, NM 87131 USA. [Massion, Pierre P.] Vanderbilt Univ, Nashville, TN USA. [Wilson, David O.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU S BP S1401 EP S1402 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 779HX UT WOS:000291769801303 ER PT J AU Liang, QL Ouyang, XS Schneider, L Zhang, JH AF Liang, Qiuli Ouyang, Xiaosen Schneider, Lonnie Zhang, Jianhua TI Reduction of mutant huntingtin accumulation and toxicity by lysosomal cathepsins D and B in neurons SO MOLECULAR NEURODEGENERATION LA English DT Article DE huntingtin; lysosome; cathepsin; autophagy ID AGGREGATE-PRONE PROTEINS; AUTOPHAGY INDUCTION; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; FRAGMENTS; DEGRADATION; PROTEASOME; CLEARANCE; APOPTOSIS AB Background: Huntington's disease is caused by aggregation of mutant huntingtin (mHtt) protein containing more than a 36 polyQ repeat. Upregulation of macroautophagy was suggested as a neuroprotective strategy to degrade mutant huntingtin. However, macroautophagy initiation has been shown to be highly efficient in neurons whereas lysosomal activities are rate limiting. The role of the lysosomal and other proteases in Huntington is not clear. Some studies suggest that certain protease activities may contribute to toxicity whereas others are consistent with protection. These discrepancies may be due to a number of mechanisms including distinct effects of the specific intermediate digestion products of mutant huntingtin generated by different proteases. These observations suggested a critical need to investigate the consequence of upregulation of individual lysosomal enzyme in mutant huntingtin accumulation and toxicity. Results: In this study, we used molecular approaches to enhance lysosomal protease activities and examined their effects on mutant huntingtin level and toxicity. We found that enhanced expression of lysosomal cathepsins D and B resulted in their increased enzymatic activities and reduced both full-length and fragmented huntingtin in transfected HEK cells. Furthermore, enhanced expression of cathepsin D or B protected against mutant huntingtin toxicity in primary neurons, and their neuroprotection is dependent on macroautophagy. Conclusions: These observations demonstrate a neuroprotective effect of enhancing lysosomal cathepsins in reducing mutant huntingtin level and toxicity in transfected cells. They highlight the potential importance of neuroprotection mediated by cathepsin D or B through macroautophagy. C1 [Liang, Qiuli; Ouyang, Xiaosen; Schneider, Lonnie; Zhang, Jianhua] Univ Alabama, Dept Pathol, Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Ouyang, Xiaosen; Zhang, Jianhua] Univ Alabama, Dept Vet Affairs, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Zhang, JH (reprint author), Univ Alabama, Dept Pathol, Ctr Free Rad Biol, Birmingham, AL 35294 USA. EM zhanja@uab.edu RI zhang, jianhua/D-3404-2009; di Ronza, Alberto/H-7674-2016 OI di Ronza, Alberto/0000-0002-9813-5143 FU CHDI foundation [NIHR01-NS064090]; UAB [NS47466, NS57098] FX This work was supported by a grant from the CHDI foundation, NIHR01-NS064090 and a VA merit award to Dr. Jianhua Zhang, and by UAB Neuroscience Core Facilities (NS47466 and NS57098). We are grateful to Drs. Michelle Gray, Mathieu Lesort, Paula Dietrich, Ioannis Dragatsis, Deanna Marchionini and Victor Darley-Usmar for technical help and discussions. NR 38 TC 18 Z9 18 U1 1 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 JUN 1 PY 2011 VL 6 AR 37 DI 10.1186/1750-1326-6-37 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 786PW UT WOS:000292321400001 PM 21631942 ER EF