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