FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Johnson, JR Menard, ME Lauderdale, TL Kosmidis, C Gordon, D Collignon, P Maslow, JN Andrasevic, AT Kuskowski, MA AF Johnson, James R. Menard, Megan E. Lauderdale, Tsai-Ling Kosmidis, Chris Gordon, David Collignon, Peter Maslow, Joel N. Andrasevic, Arjana Tambic Kuskowski, Michael A. CA Trans-Global Initiative TI Global Distribution and Epidemiologic Associations of Escherichia coli Clonal Group A, 1998-2007 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID URINARY-TRACT-INFECTIONS; TRIMETHOPRIM-SULFAMETHOXAZOLE RESISTANCE; EXTRAINTESTINAL INFECTIONS; UNCOMPLICATED CYSTITIS; MOLECULAR EPIDEMIOLOGY; NEONATAL MENINGITIS; COMMUNITY; PYELONEPHRITIS; O-18-K1-H7; PREVALENCE AB Escherichia coli clonal group A (CGA) was first reported in 2001 as an emerging multidrug-resistant extraintestinal pathogen. Because CGA has considerable implications for public health, we examined the trends of its global distribution, clinical associations, and temporal prevalence for the years 1998-2007. We characterized 2,210 E. coli extraintestinal clinical isolates from 32 centers on 6 continents by CGA status for comparison with trimethoprim/sulfamethoxazole (TMP/SMZ) phenotype, specimen type, inpatient/outpatient source, and adult/child host; we adjusted for clustering by center. CGA prevalence varied greatly by center and continent, was strongly associated with TMP/SMZ resistance but not with other epidemiologic variables, and exhibited no temporal prevalence trend. Our findings indicate that CGA is a prominent, primarily TMP/SMZ-resistant extraintestinal pathogen concentrated within the Western world, with considerable pathogenic versatility. The stable prevalence of CGA over time suggests full emergence by the late 1990s, followed by variable endemicity worldwide as an antimicrobial drug resistant public health threat. C1 [Johnson, James R.; Menard, Megan E.; Kuskowski, Michael A.] VA Med Ctr, Minneapolis, MN 55417 USA. [Johnson, James R.] Univ Minnesota, Infect Dis Fellowship Program, Minneapolis, MN USA. [Lauderdale, Tsai-Ling] Natl Hlth Res Inst, Zhunan, Taiwan. [Kosmidis, Chris] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Gordon, David; Collignon, Peter] Australian Natl Univ, Canberra, ACT, Australia. [Collignon, Peter] Canberra Hosp, Canberra, ACT, Australia. [Maslow, Joel N.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Maslow, Joel N.] Univ Penn, Philadelphia, PA 19104 USA. [Andrasevic, Arjana Tambic] Univ Hosp Infect Dis, Zagreb, Croatia. RP Johnson, JR (reprint author), VA Med Ctr, 1 Vet Dr, Minneapolis, MN 55417 USA. EM johns007@umn.edu RI Lauderdale, Tsai-Ling/B-2660-2010; Toniolo, Antonio/B-4103-2015 OI Toniolo, Antonio/0000-0003-3008-2126; Kosmidis, Chris/0000-0003-0662-1265 FU Office of Research and Development, Medical Research Service, US Department of Veterans Affairs; Merck, Inc.; Rochester Medical Group FX This material is based on work supported by Office of Research and Development, Medical Research Service, US Department of Veterans Affairs (J.R.J.). J.R.J. has received research support (grant and contract) from Merck, Inc., and Rochester Medical Group. NR 25 TC 19 Z9 19 U1 1 U2 8 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2011 VL 17 IS 11 BP 2001 EP 2009 DI 10.3201/eid1711.110488 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 843KI UT WOS:000296670300002 PM 22099087 ER PT J AU Roemer, FW Kwoh, CK Hannon, MJ Crema, MD Moore, CE Jakicic, JM Green, SM Guermazi, A AF Roemer, Frank W. Kwoh, C. Kent Hannon, Michael J. Crema, Michel D. Moore, Carolyn E. Jakicic, John M. Green, Stephanie M. Guermazi, Ali TI Semiquantitative assessment of focal cartilage damage at 3 T MRI: A comparative study of dual echo at steady state (DESS) and intermediate-weighted (IW) fat suppressed fast spin echo sequences SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE MRI; Cartilage; Knee; Focal defect; Osteoarthritis ID ARTICULAR-CARTILAGE; WATER-EXCITATION; NATURAL-HISTORY; KNEE; DEFECTS; OSTEOARTHRITIS; PATHOLOGY; PROTOCOL; 3-TESLA; LESIONS AB Purpose: The aim of the study was to compare semiquantitative assessment of focal cartilage damage using the dual echo at steady state (DESS)- and intermediate-weighted (IW) fat suppressed (fs) sequences at 3 T MRI. Methods: Included were 201 subjects aged 35-65 with frequent knee pain. MRI was performed with the same sequence protocol as in the Osteoarthritis Initiative (OAI): sagittal IW fs, triplanar DESS and coronal IW sequences. Cartilage status was scored according to the WORMS system using all five sequences. A total of 243 focal defects were detected. In an additional consensus reading, the lesions were evaluated side-by-side using only the sagittal DESS and IW fs sequences. Lesion conspicuity was graded from 0 to 3, intrachondral signal changes adjacent to the defect were recorded and the sequence that depicted the lesion with larger diameter was noted. Wilcoxon signed-rank tests, controlled for clustering by person, were used to examine differences between the sequences. Results: 37 (17.5%) of the scorable lesions were located in the medial tibio-femoral (TF), 48 (22.7%) in the lateral TF and 126 (59.7%) in the patello-femoral compartment. 82.5% were superficial and 17.5% full-thickness defects. Conspicuity was superior for the IW sequence (p < 0.001). The DESS sequence showed moreassociated intrachondral signal changes (p < 0.001). In 103 (48.8%) cases, the IW fs sequence depicted the lesions as being larger (p < 0.001). Conclusions: The IW fs sequence detected more and larger focal cartilage defects than the DESS. More intrachondral signal changes were observed with the DESS. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Roemer, Frank W.; Crema, Michel D.; Guermazi, Ali] Boston Univ, Dept Radiol, Med Ctr, Quantitat Imaging Ctr, Boston, MA 02118 USA. [Roemer, Frank W.] Klinikum Augsburg, Dept Radiol, Augsburg, Germany. [Kwoh, C. Kent; Hannon, Michael J.; Green, Stephanie M.] Univ Pittsburgh, Div Rheumatol & Clin Immunol, Sch Med, Pittsburgh, PA 15260 USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Moore, Carolyn E.] Texas Womans Univ, Dept Nutr & Food Sci, Denton, TX 76204 USA. [Jakicic, John M.] Univ Pittsburgh, Dept Hlth & Phys Act, Pittsburgh, PA 15260 USA. RP Roemer, FW (reprint author), Boston Univ, Dept Radiol, Med Ctr, Quantitat Imaging Ctr, FGH Bldg,3rd Floor,820 Harrison Ave, Boston, MA 02118 USA. EM froemer@bu.edu FU Beverage Institute for Health Wellness FX The JOG study is funded by a grant from the Beverage Institute for Health & Wellness. NR 20 TC 33 Z9 33 U1 3 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD NOV PY 2011 VL 80 IS 2 BP E126 EP E131 DI 10.1016/j.ejrad.2010.07.025 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 839JC UT WOS:000296360500020 PM 20833493 ER PT J AU Golden-Mason, L Bambha, KM Cheng, LL Howell, CD Taylor, MW Clark, PJ Afdhal, N Rosen, HR AF Golden-Mason, Lucy Bambha, Kiran M. Cheng, Linling Howell, Charles D. Taylor, Milton W. Clark, Paul J. Afdhal, Nezam Rosen, Hugo R. CA Virahep-C Study Grp TI Natural Killer Inhibitory Receptor Expression Associated with Treatment Failure and Interleukin-28B Genotype in Patients with Chronic Hepatitis C SO HEPATOLOGY LA English DT Article ID VIRUS-INFECTION; TREATMENT RESPONSE; ANTIVIRAL THERAPY; GENE-EXPRESSION; INTERFERON; IL28B; RIBAVIRIN; CELLS; PEGINTERFERON; PREDICTS AB Natural killer (NK) cells constitute a first line of defense against viral infections; their function is governed by the integration of signals from multiple activating and inhibitory surface receptors. We hypothesized that because NKs become rapidly activated by cytokines, response to anti-hepatitis C virus (HCV) therapy would be predicted by the phenotype and function of NKs. We used a cohort of 101 patients (55 African, 46 Caucasian-American) who received pegylated-interferon (IFN) and ribavirin for 48 weeks. Multi-parameter FACS analysis was used to examine relative expression of 14 different inhibitory/activating receptors. Interleukin (IL)-28B genotyping (rs12979860) was also performed. Pretreatment levels of inhibitory receptors CD158a, CD158b, and CD158e were higher in patients who demonstrated poor viral decline within the first 28 days of therapy. Higher expression levels of inhibitory receptors NKG2A, CD158b, and CD158e were demonstrable in patients who failed to achieve sustained virologic response (SVR). Patients carrying the IL-28B T allele had higher NKG2A expression on effector NKs. We created a mathematical regression model incorporating race, viral level, and two inhibitory receptors. The area-under-the curve was 0.88, which is highly predictive of SVR. Moreover, the model performed complementarily with IL-28B across the CC, CT, and TT genotypes. Purified NKG2A neg NKs treated with pegylated-IFN-alpha for 4 hours demonstrated higher levels of IFN-c-inducible protein-10 (IP-10) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) compared with their NKG2A(pos) counterparts. Conclusions: These results provide novel insights into the associations of NK phenotype with IL-28B genotype and gene expression patterns, as well as the role of NKs in mediating IFN-induced viral clearance of chronic HCV infection. (HEPATOLOGY 2011;54:1559-1569) C1 [Golden-Mason, Lucy; Bambha, Kiran M.; Cheng, Linling; Rosen, Hugo R.] Univ Colorado, Dept Med, Div Gastroenterol & Hepatol, Hepatitis Ctr C, Denver, CO USA. [Golden-Mason, Lucy; Bambha, Kiran M.; Cheng, Linling; Rosen, Hugo R.] Natl Jewish Hosp, Denver, CO USA. [Golden-Mason, Lucy] Univ Colorado, Integrated Program Immunol, Denver, CO 80202 USA. [Howell, Charles D.] Univ Maryland, Baltimore Sch Med, Baltimore, MD 21201 USA. [Taylor, Milton W.] Indiana Univ, Dept Biol, Bloomington, IN USA. [Clark, Paul J.] Duke Univ, Med Ctr, Sch Med, Div Gastroenterol, Durham, NC 27710 USA. [Clark, Paul J.] Duke Clin Res Inst, Durham, NC USA. [Afdhal, Nezam] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Rosen, Hugo R.] Denver VA Med Ctr, Denver, CO USA. RP Rosen, HR (reprint author), Div GI Hepatol B 158, Acad Off Bldg 1,12631 E 17th Ave,Rm 7614,POB 6511, Aurora, CO 80045 USA. EM hugo.rosen@ucdenver.edu RI Clark, Paul/A-1480-2012 OI Clark, Paul/0000-0002-1821-4969 FU NIDDK [1 K24 DK072036-01]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Cancer Institute (NCI) with Roche Laboratories, Inc.; National Health and Medical Research Council of Australia; Duke Clinical Research Institute; Richard Boebel Family Fund; National Centre in HIV Epidemiology and Clinical Research (now the Kirby Institute for Infection and Immunity in Society), University of New South Wales, Australia; [RO1 DK071560]; [U01 DK60329]; [U01 DK60340]; [U01 DK60324]; [U01 DK60344]; [U01 DK60327]; [U01 DK60335]; [U01 DK60352]; [U01 DK60342]; [U01 DK60345]; [U01 DK60309]; [U01 K60346]; [U01 DK60349]; [U01 DK60341] FX Supported by RO1 DK071560 (to H. R. R.) and by NIDDK 1 K24 DK072036-01. (to. C. D. H). This study was funded as a cooperative agreement by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Intramural Research Program of the National Cancer Institute (NCI) with further support under a Cooperative Research and Development Agreement (CRADA) with Roche Laboratories, Inc. A complete listing of participants in the Virahep-C study is given in Reference 5. Grant numbers: U01 DK60329, U01 DK60340, U01 DK60324, U01 DK60344, U01 DK60327, U01 DK60335, U01 DK60352, U01 DK60342, U01 DK60345, U01 DK60309, U01 DK60346, U01 DK60349, U01 DK60341. Dr. Howell is supported by NIDDK 1 K24 DK072036-01. Dr. Clark received funding support from the National Health and Medical Research Council of Australia, the Duke Clinical Research Institute, the Richard Boebel Family Fund, the National Centre in HIV Epidemiology and Clinical Research (now the Kirby Institute for Infection and Immunity in Society), University of New South Wales, Australia. NR 26 TC 42 Z9 46 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2011 VL 54 IS 5 BP 1559 EP 1569 DI 10.1002/hep.24556 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 840LX UT WOS:000296443100010 PM 21983945 ER PT J AU Pellegrini, CN Scheinman, MM Badhwar, N AF Pellegrini, Cara N. Scheinman, Melvin M. Badhwar, Nitish TI Idiopathic epicardial ventricular tachycardia with origin remote from vascular structures SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Idiopathic ventricular tachycardia; Epicardial; Perivascular; Catheter ablation ID CATHETER ABLATION; OUTFLOW TRACT; IDENTIFY; VALSALVA; SINUS; SITE AB We report a case of a patient with idiopathic left ventricular tachycardia (VT) successfully ablated from the epicardial aspect of the left ventricle, after a previous failed endocardial ablation. The VT appeared to be catecholamine sensitive. An excellent epicardial pacemap was found in the midlateral region of the left ventricle, remote from vascular structures. Following ablation, the patient discontinued antiarrhythmic drug use and has not experienced any recurrence of VT for more than 2 1/2 years. (C) 2011 Elsevier Inc. All rights reserved. C1 [Pellegrini, Cara N.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Pellegrini, Cara N.; Scheinman, Melvin M.; Badhwar, Nitish] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Pellegrini, CN (reprint author), San Francisco VA Med Ctr, Dept Med, 4150 Clement St,111C, San Francisco, CA 94121 USA. EM pellegrinic@medicine.ucsf.edu FU American Heart Association FX Supported in part by a grant from the American Heart Association NR 13 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD NOV-DEC PY 2011 VL 44 IS 6 BP 792 EP 795 DI 10.1016/j.jelectrocard.2011.01.007 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 843GO UT WOS:000296660500031 PM 21419422 ER PT J AU Londono, DC Wuerstle, M Thomas, AA Tsu, JW Danial, T Chien, G AF Londono, Diana C. Wuerstle, Melanie Thomas, Anil A. Tsu, Jin-Wen Danial, Tarek Chien, Gary TI ACCURACY AND IMPLICATION OF PERCUTANEOUS RENAL BIOPSY IN THE MANAGEMENT OF RENAL MASSES SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Londono, Diana C.; Wuerstle, Melanie; Thomas, Anil A.; Danial, Tarek; Chien, Gary] W Los Angeles Vet Affairs Med Ctr, Dept Urol, Los Angeles, CA 90073 USA. [Tsu, Jin-Wen] Kaiser Permanente So Calif, Dept Res & Evaluat, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD NOV PY 2011 VL 25 SU 1 BP A95 EP A95 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 844ZI UT WOS:000296792200292 ER PT J AU Higgs, MH Spain, WJ AF Higgs, Matthew H. Spain, William J. TI Kv1 channels control spike threshold dynamics and spike timing in cortical pyramidal neurones SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID AXON INITIAL SEGMENT; ACTION-POTENTIAL INITIATION; HIGH-FREQUENCY OSCILLATIONS; AVIAN COCHLEAR NUCLEUS; COINCIDENCE DETECTION; FAST RIPPLES; IN-VIVO; EPILEPTIC HIPPOCAMPUS; POTASSIUM CHANNELS; AUDITORY NEURONS AB Previous studies showed that cortical pyramidal neurones (PNs) have a dynamic spike threshold that functions as a high-pass filter, enhancing spike timing in response to high-frequency input. While it is commonly assumed that Na(+) channel inactivation is the primary mechanism of threshold accommodation, the possible role of K(+) channel activation in fast threshold changes has not been well characterized. The present study tested the hypothesis that low-voltage activated Kv1 channels affect threshold dynamics in layer 2-3 PNs, using alpha-dendrotoxin (DTX) or 4-aminopyridine (4-AP) to block these conductances. We found that Kv1 blockade reduced the dynamic changes of spike threshold in response to a variety of stimuli, including stimulus-evoked synaptic input, current steps and ramps of varied duration, and noise. Analysis of the responses to noise showed that Kv1 channels increased the coherence of spike output with high-frequency components of the stimulus. A simple model demonstrates that a dynamic spike threshold can account for this effect. Our results show that the Kv1 conductance is a major mechanism that contributes to the dynamic spike threshold and precise spike timing of cortical PNs. C1 [Higgs, Matthew H.; Spain, William J.] Dept Vet Affairs Med Ctr, Neurol Sect, Seattle, WA USA. [Higgs, Matthew H.; Spain, William J.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. [Spain, William J.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. RP Higgs, MH (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Neurol Mail Stop 127,1660 S Columbian Way, Seattle, WA 98108 USA. EM higgsm@uw.edu FU US Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory; Veterans Affairs Merit Review; Veterans Affairs Epilepsy Centre of Excellence FX This material is based on work supported by the US Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory Research Program. Funding was provided by a Veterans Affairs Merit Review to W.J.S. and a Veterans Affairs Epilepsy Centre of Excellence. We thank Robert Foehring and Adrienne Fairhall for helpful discussions, Steve Redman for helpful comments on the manuscript, and Susan Usher for excellent technical assistance. NR 60 TC 41 Z9 42 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV PY 2011 VL 589 IS 21 BP 5125 EP 5142 DI 10.1113/jphysiol.2011.216721 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 839MA UT WOS:000296369000012 PM 21911608 ER PT J AU Schacht, JP Randall, PK Waid, LR Baros, AM Latham, PK Wright, TM Myrick, H Anton, RF AF Schacht, Joseph P. Randall, Patrick K. Waid, L. R. Baros, Alicia M. Latham, Patricia K. Wright, Tara M. Myrick, Hugh Anton, Raymond F. TI Neurocognitive Performance, Alcohol Withdrawal, and Effects of a Combination of Flumazenil and Gabapentin in Alcohol Dependence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcoholism; Anticonvulsant; gamma-Aminobutyric Acid; Neurocognitive; Withdrawal ID ETHANOL WITHDRAWAL; GABA(A) RECEPTORS; SUBSTANCE-ABUSE; MULTIPLE DETOXIFICATIONS; COGNITIVE IMPAIRMENT; HEALTHY-VOLUNTEERS; GENE-EXPRESSION; OUTCOMES; CARBAMAZEPINE; INTERFERENCE AB Background: Among some alcohol-dependent individuals, early alcohol abstinence is marked by alcohol withdrawal (AW), a phenomenon mediated by GABA and glutamate signaling. We previously reported that a combination of 2 medications that affect GABA and glutamate tone, gabapentin and flumazenil, more effectively reduced drinking among individuals with higher pretreatment AW (Anton et al., 2009). This study evaluated whether this finding is related to changes in neurocognitive performance, which is also affected by cortical GABA and glutamate tone. Methods: Neurocognitive performance was assessed at baseline and twice during the first week of treatment among 60 alcohol-dependent participants in the previously published clinical trial. Results: AW was associated with poorer baseline performance on 4 of 8 measures, and individuals with higher baseline AW who received the gabapentin and flumazenil combination demonstrated greater improvement on a measure of response inhibition than those with lower AW or those who received a combination of placebos. Improvement in response inhibition during the first week and medication group interacted in their effect on subsequent drinking, such that improvement predicted greater abstinence only among individuals who received gabapentin and flumazenil. Improvement on other neurocognitive measures was neither differentially impacted by medication or baseline AW nor related to subsequent drinking. Conclusions: Taken together, these data suggest that acute AW accounts for a small proportion of variance in neurocognitive performance, that gabapentin and flumazenil slightly improve response inhibition during early abstinence, and that such improvement may somewhat reduce later drinking. However, these medications may not affect other neurocognitive domains. C1 [Schacht, Joseph P.; Randall, Patrick K.; Waid, L. R.; Baros, Alicia M.; Latham, Patricia K.; Wright, Tara M.; Myrick, Hugh; Anton, Raymond F.] Med Univ S Carolina, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. [Wright, Tara M.; Myrick, Hugh] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Schacht, JP (reprint author), Med Univ S Carolina, Ctr Drug & Alcohol Programs, 67 President St,MSC 861, Charleston, SC 29425 USA. EM schacht@musc.edu FU Hythiam, Inc.; National Institute on Alcohol Abuse and Alcoholism [T32 AA007474, K05 AA017435] FX This work was conducted under an unrestricted grant from Hythiam, Inc. JPS was supported by an institutional training grant (T32 AA007474) and RFA by a senior scientist research and mentorship award (K05 AA017435) from the National Institute on Alcohol Abuse and Alcoholism. NR 68 TC 5 Z9 5 U1 6 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2011 VL 35 IS 11 BP 2030 EP 2038 DI 10.1111/j.1530-0277.2011.01554.x PG 9 WC Substance Abuse SC Substance Abuse GA 841SG UT WOS:000296532800014 PM 21631542 ER PT J AU Schlansky, B Sonnenberg, A AF Schlansky, Barry Sonnenberg, Amnon TI Epidemiology of Noncardia Gastric Adenocarcinoma in the United States SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HELICOBACTER-PYLORI INFECTION; STOMACH-CANCER MORTALITY; US ADULTS; CARDIA; TRENDS; ESOPHAGEAL; PREVENTION; BURDEN; RISK AB OBJECTIVES: Adenocarcinomas of the cardia (International Classification of Diseases (ICD)-9 code 151.0) and stomach (ICD-9 codes 151.1-151.9) are frequently grouped together in epidemiologic statistics, but are clearly distinct diseases. The objective of this study was to describe the current epidemiology of noncardia gastric cancer (noncardia gastric adenocarcinoma (NCGA)) in the United States. METHODS: Rates of NCGA in the United States from 1997 to 2008 were analyzed in three national databases: the Surveillance, Epidemiology, and End Results registry was used for incidence, the Healthcare Costs and Utilization Project for hospitalizations, and the Compressed Mortality File for mortality. Population-based rates were calculated and age-adjusted to the US 2000 population using direct standardization. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated and adjusted for confounders with the Mantel-Haenszel method. RESULTS: Annually, NCGA was associated with 18,873 incident cases, 17,284 hospitalizations for principal discharge diagnoses, 31,354 hospitalizations for all-listed diagnoses, and 11,562 deaths. Incidence was greater in men (OR = 1.56, CI = 1.53-1.59) and non-White races (OR = 2.38, 2.33-2.43). Hospitalization was more common in men (1.82, 1.81-1.83) and non-White races (2.13, 2.10-2.15). Mortality was more common in men (1.83, 1.81-1.86) and non-White races (2.23, 2.20-2.26). NCGA rates showed a marked age-dependent rise (P < 0.001). Hospitalization and mortality were greatest in the Northeast region of the United States (P < 0.001). CONCLUSIONS: Epidemiologic patterns of NCGA were congruent in three national databases. Older age, male gender, non-White race, and residence in the Northeast region were associated with increased risk. These patterns may reflect the underlying variations in Helicobacter pylori, lifestyle, and environmental exposures. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Schlansky, Barry; Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Dept Med, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US,Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 39 TC 29 Z9 31 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2011 VL 106 IS 11 BP 1978 EP 1985 DI 10.1038/ajg.2011.213 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 844ZD UT WOS:000296791700014 PM 22008896 ER PT J AU Gerlock, AA Grimesey, JL Pisciotta, AK Harel, O AF Gerlock, April A. Grimesey, Jackie L. Pisciotta, Alisa K. Harel, Ofer TI Documentation of Screening for Perpetration of Intimate Partner Violence in Male Veterans with PTSD SO AMERICAN JOURNAL OF NURSING LA English DT Article DE documentation; intimate partner violence; partner abuse; perpetrators; posttraumatic stress disorder; screening; veterans ID DOMESTIC VIOLENCE; ABUSED WOMEN; HEALTH; FAMILY; CARE; SETTINGS; GUIDELINES; BEHAVIORS; SUICIDE; SYSTEM AB Background: Men seeking care for posttraumatic stress disorder (PTSD) are believed to have high rates of relationship conflict and intimate partner violence (IPV). But little is known about screening for IPV perpetration in this population. Objective: In phase one of a two-phase study of male veterans treated for PTSD, the primary objective was to determine how many veterans' records showed documentation that they'd been screened for IPV perpetration. The secondary objective was to count the total number of screenings and to determine whether an initial screening affected future screenings. Methods: For this retrospective cohort study, a stratified random sample of 10% (N = 507) of all male veterans receiving treatment for PTSD at a U.S. Department of Veterans Affairs health care facility in a five-year period (November 2002 to November 2007) was selected and more than 70,000 progress notes were reviewed. The presence or absence of a documented screening for IPV perpetration in each record was noted and a Spearman rank correlation test to determine the relationship between the documentation of a first screening and future screenings was performed. Results: Of the 507 records examined, 120 (24%) showed documentation of screening for IPV perpetration. Of those, 73 (61%) showed positive results for IPV perpetration, and 61 (51%) showed more than one screening. Documentation of screening was most likely to have occurred at the veteran's initial appointment (71%) and in an outpatient mental health setting (72%); IPV perpetration was determined most often as the result of a provider's inquiry (45%). There was a total of 415 screenings, including 356 in records in which there was more than one screening. The documentation of a single screening for IPV perpetration was significantly correlated with the documentation of subsequent screenings and with IPV perpetration determination (Spearman rank correlation = 0.611, P < 0.001). Also, veterans with documented IPV perpetration and high rates of relationship conflict accessed the health care system twice as often as those without such documentation. Conclusions: In the sample analyzed, fewer than a quarter of male veterans with PTSD had a documented screening for IPV perpetration. Also, because those identified as IPV perpetrators accessed the health care system at a higher rate than those not so identified and repeated screenings were associated with a higher rate of IPV perpetrator determinations, health care providers should be made more aware of opportunities for screening for IPV in this population. C1 [Gerlock, April A.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Grimesey, Jackie L.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Tacoma, WA USA. [Harel, Ofer] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP Gerlock, AA (reprint author), Univ Washington, Sch Nursing, Seattle, WA 98195 USA. EM april.gerlock@va.gov RI Schueter, nicos/A-3625-2014 FU Office of Research and Development, Nursing Research Initiative, Department of Veterans Affairs [NRI 04-040]; University of Connecticut FX This material is based upon the work supported by the Office of Research and Development, Nursing Research Initiative (NRI 04-040), Department of Veterans Affairs, and by the University of Connecticut. The authors acknowledge Anne Ganley, Jeff Edleson, and Patricia Betrus for their assistance in project design and manuscript development; they received a consultation fee from the grant. NR 37 TC 4 Z9 4 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD NOV PY 2011 VL 111 IS 11 BP 26 EP 32 DI 10.1097/01.NAJ.0000407296.10524.d7 PG 7 WC Nursing SC Nursing GA 842HG UT WOS:000296586500017 PM 22005050 ER PT J AU Gerlock, AA Grimesey, JL Pisciotta, AK Harel, O AF Gerlock, April A. Grimesey, Jackie L. Pisciotta, Alisa K. Harel, Ofer TI Ask a Few More Questions SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material ID INTIMATE PARTNER VIOLENCE; NURSES; SCREEN; WOMEN C1 [Gerlock, April A.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Grimesey, Jackie L.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Tacoma, WA USA. [Harel, Ofer] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP Gerlock, AA (reprint author), Univ Washington, Sch Nursing, Seattle, WA 98195 USA. EM april.gerlock@va.gov FU NIMH NIH HHS [K01 MH087219] NR 18 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD NOV PY 2011 VL 111 IS 11 BP 35 EP 39 DI 10.1097/01.NAJ.0000407299.00222.ac PG 5 WC Nursing SC Nursing GA 842HG UT WOS:000296586500018 PM 22030925 ER PT J AU Malandraki, GA Hind, JA Gangnon, R Logemann, JA Robbins, J AF Malandraki, Georgia A. Hind, Jacqueline A. Gangnon, Ronald Logemann, Jeri A. Robbins, JoAnne TI The Utility of Pitch Elevation in the Evaluation of Oropharyngeal Dysphagia: Preliminary Findings SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE swallowing; voice; cricothyroid muscle; aspiration; pitch elevation ID PENETRATION-ASPIRATION SCALE; SUPERIOR LARYNGEAL NERVE; MULTIPLE IMPUTATION; VOICE; DISPLACEMENT; CLINICIAN; ANATOMY; STROKE; REFLEX; ADULTS AB Purpose: To evaluate the utility of a pitch elevation task in the assessment of oropharyngeal dysphagia. Method: This study was a pilot prospective cohort study including 40 consecutive patients (16 male and 24 female) who were referred by their physician for a swallowing evaluation. Patients were evaluated with a noninstrumental clinical examination and a videofluoroscopic swallow study, and participated in a pitch elevation task during videofluoroscopic image acquisition. Relationships between pitch elevation measurements (acoustic and perceptual) and swallow parameters (penetration/aspiration and residue) were investigated. Results: Results of this pilot study revealed that both maximum fundamental frequency (F(o)) and perceptual evaluation of pitch elevation independently significantly predicted Penetration-Aspiration Scale scores for thin liquid swallows (p = .01 and .03, respectively). Vocal range (average pitch to falsetto) was not sensitive in predicting likelihood of oropharyngeal dysphagia. Conclusions: Findings indicate that reduced pitch elevation can be indicative of reduced airway protection and swallowing impairment in some dysphagia patients and may be a useful supplement to dysphagia screening and diagnosis. Further investigation is warranted to determine the optimal utility of this procedure for different diagnostic categories of patients. C1 [Malandraki, Georgia A.; Hind, Jacqueline A.; Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Malandraki, Georgia A.; Hind, Jacqueline A.; Gangnon, Ronald; Robbins, JoAnne] Univ Wisconsin, Madison, WI 53706 USA. [Malandraki, Georgia A.] Columbia Univ, Teachers Coll, New York, NY 10027 USA. [Logemann, Jeri A.] Northwestern Univ, Evanston, IL USA. RP Malandraki, GA (reprint author), William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. EM malandraki@tc.columbia.edu NR 38 TC 4 Z9 5 U1 0 U2 1 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1058-0360 J9 AM J SPEECH-LANG PAT JI Am. J. Speech-Lang. Pathol. PD NOV 1 PY 2011 VL 20 IS 4 BP 262 EP 268 DI 10.1044/1058-0360(2011/10-0097) PG 7 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 844CE UT WOS:000296724500002 PM 21813823 ER PT J AU Lincoln, R Rosenthal, CF Malte, CA Simpson, T AF Lincoln, Randi Rosenthal, Christina F. Malte, Carol A. Simpson, Tracy TI A Pilot Study of Memory Impairment Associated with Discrepancies between Retrospective and Daily Recall of Alcohol Consumption SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID INTERACTIVE VOICE RESPONSE; AUTOBIOGRAPHICAL MEMORY; MEASURE DRINKING; TECHNOLOGY AB Prior studies have found discrepancies between daily report and retrospective recall of alcohol use. One possible explanation is that there may be an association between memory impairment and alcohol consumption recall errors. Should this possibility be substantiated it could have implications for the types of assessments conducted in alcohol treatment trials. The current study evaluated the degree to which memory impairment, as measured by the California Verbal Learning Test-II, predicted day-to-day discrepancies between daily Interactive Voice Response monitoring and retrospective recall of alcohol use assessed with a 42-day version of the Form-90. Significant differences were detected in absolute difference in days drinking across the two measurement methods between participants scoring above and below population means on two measures of immediate memory ability. Correlations between the absolute difference in days drinking and immediate memory ability and long-delay memory indices approached significance. There were no significant associations between memory indices and discrepancies in reports of standard drink units. These preliminary results suggest that verbal memory difficulties common in this population may result in inaccurate reports of days drinking for some individuals. (Am J Addict 2011;20:568-574) C1 [Lincoln, Randi] VA Puget Sound Hlth Care Syst, Spinal Cord Injury Ctr Excellence, Seattle, WA 98108 USA. [Rosenthal, Christina F.; Simpson, Tracy] Seattle Inst Biomed & Clin Res, Seattle, WA USA. [Malte, Carol A.; Simpson, Tracy] Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [Simpson, Tracy] VISN 20 Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Simpson, Tracy] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Simpson, T (reprint author), VA Puget Sound Hlth Care Syst, Spinal Cord Injury Ctr Excellence, 1660 S Columbian Way ATC 116-S, Seattle, WA 98108 USA. EM Tracy.Simpson@va.gov NR 20 TC 5 Z9 5 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD NOV-DEC PY 2011 VL 20 IS 6 BP 568 EP 574 DI 10.1111/j.1521-0391.2011.00178.x PG 7 WC Substance Abuse SC Substance Abuse GA 840EB UT WOS:000296420000011 PM 21999504 ER PT J AU Wallace, AW Au, S Cason, BA AF Wallace, Arthur W. Au, Selwyn Cason, Brian A. TI How Often Should Atenolol Be Dosed for Perioperative beta-Blockade? Reply SO ANESTHESIOLOGY LA English DT Letter ID MORTALITY C1 [Wallace, Arthur W.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Wallace, AW (reprint author), San Francisco VA Med Ctr, San Francisco, CA USA. EM awallace@cardiacengineering.com NR 4 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2011 VL 115 IS 5 BP 1140 EP 1141 DI 10.1097/ALN.0b013e3182334092 PG 4 WC Anesthesiology SC Anesthesiology GA 842AR UT WOS:000296558400040 ER PT J AU Lee, BY Song, Y McGlone, SM Bailey, RR Feura, JM Tai, JHY Lewis, GJ Wiringa, AE Smith, KJ Muder, RR Harrison, LH Piraino, B AF Lee, B. Y. Song, Y. McGlone, S. M. Bailey, R. R. Feura, J. M. Tai, J. H. Y. Lewis, G. J. Wiringa, A. E. Smith, K. J. Muder, R. R. Harrison, L. H. Piraino, B. TI The economic value of screening haemodialysis patients for methicillin-resistant Staphylococcus aureus in the USA SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article DE Cost-effectiveness; economics; haemodialysis; methicillin-resistant Staphylococcus aureus; surveillance ID HEALTH-CARE WORKERS; DIALYSIS PATIENTS; SURGERY PATIENTS; UNITED-STATES; MUPIROCIN; COLONIZATION; INFECTIONS; PREVALENCE; CARRIAGE; CALCIUM AB Methicillin-resistant Staphylococcus aureus (MRSA) can cause severe infections in patients undergoing haemodialysis. Routine periodic testing of haemodialysis patients and attempting to decolonize those who test positive may be a strategy to prevent MRSA infections. The economic value of such a strategy has not yet been estimated. We constructed a Markov computer simulation model to evaluate the economic value of employing routine testing (agar-based or PCR) at different MRSA prevalence, spontaneous clearance, costs of decolonization and decolonization success rates, performed every 3, 6 or 12 months. The model showed periodic MRSA surveillance with either test to be cost-effective (incremental cost-effectiveness ratio <=$50 000/quality-adjusted life-year) for all conditions tested. Agar surveillance was dominant (i.e. less costly and more effective) at an MRSA prevalence >= 10% and a decolonization success rate >= 25% for all decolonization treatment costs tested with no spontaneous clearance. PCR surveillance was dominant when the MRSA prevalence was >= 20% and decolonization success rate was >= 75% with no spontaneous clearance. Routine periodic testing and decolonization of haemodialysis patients for MRSA may be a cost-effective strategy over a wide range of MRSA prevalences, decolonization success rates, and testing intervals. C1 [Lee, B. Y.; Song, Y.; McGlone, S. M.; Bailey, R. R.; Feura, J. M.; Tai, J. H. Y.; Lewis, G. J.; Wiringa, A. E.] Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR, Pittsburgh, PA 15213 USA. [Lee, B. Y.; Song, Y.; McGlone, S. M.; Bailey, R. R.; Feura, J. M.; Tai, J. H. Y.; Lewis, G. J.; Wiringa, A. E.] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15213 USA. [Lee, B. Y.; Song, Y.; McGlone, S. M.; Bailey, R. R.; Feura, J. M.; Tai, J. H. Y.; Lewis, G. J.; Wiringa, A. E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Smith, K. J.] Univ Pittsburgh, Sect Decis Sci & Clin Syst Modeling, Pittsburgh, PA 15213 USA. [Muder, R. R.] Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Div Infect Dis, Pittsburgh, PA 15213 USA. [Harrison, L. H.] Univ Pittsburgh, Sch Med, Infect Dis Epidemiol Res Unit, Pittsburgh, PA 15213 USA. [Piraino, B.] Univ Pittsburgh, Div Nephrol, Pittsburgh, PA 15213 USA. RP Lee, BY (reprint author), Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR, 200 Meyran Ave,Suite 200, Pittsburgh, PA 15213 USA. EM byl1@pitt.edu OI Piraino, Beth/0000-0001-5061-0841; Slayton, Rachel/0000-0003-4699-8040 FU National Institute of General Medical Sciences Models of Infectious Disease Agent Study (MIDAS) [5U54GM088491-02]; Pennsylvania Department of Health (DOH) [4100047864] FX This work was supported by the National Institute of General Medical Sciences Models of Infectious Disease Agent Study (MIDAS) grant 5U54GM088491-02 and the Pennsylvania Department of Health (DOH) grant 4100047864. The funders had no role in the design and conduct of the study, collection, management, analysis and interpretation of the data, or preparation, review or approval of the manuscript. NR 21 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD NOV PY 2011 VL 17 IS 11 BP 1717 EP 1726 DI 10.1111/j.1469-0691.2011.03525.x PG 10 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 846PS UT WOS:000296916300026 PM 21595796 ER PT J AU Fredericks, WJ McGarvey, T Wang, HY Lal, P Puthiyaveettil, R Tomaszewski, J Sepulveda, J Labelle, E Weiss, JS Nickerson, ML Kruth, HS Brandt, W Wessjohann, LA Malkowicz, SB AF Fredericks, William J. McGarvey, Terry Wang, Huiyi Lal, Priti Puthiyaveettil, Raghunath Tomaszewski, John Sepulveda, Jorge Labelle, Ed Weiss, Jayne S. Nickerson, Michael L. Kruth, Howard S. Brandt, Wolfgang Wessjohann, Ludger A. Malkowicz, S. Bruce TI The Bladder Tumor Suppressor Protein TERE1 (UBIAD1) Modulates Cell Cholesterol: Implications for Tumor Progression SO DNA AND CELL BIOLOGY LA English DT Article ID PROSTATE-CANCER CELLS; VITAMIN-K; APOLIPOPROTEIN-E; CARCINOMA-CELLS; CORNEAL-DYSTROPHY; OXIDATIVE STRESS; MITOCHONDRIAL CHOLESTEROL; HEPATOCELLULAR-CARCINOMA; XENOBIOTIC RECEPTOR; MACROPHAGE ABCA1 AB Convergent evidence implicates the TERE1 protein in human bladder tumor progression and lipid metabolism. Previously, reduced TERE1 expression was found in invasive urologic cancers and inhibited cell growth upon re-expression. A role in lipid metabolism was suggested by TERE1 binding to APOE, a cholesterol carrier, and to TBL2, a candidate protein in triglyceride disorders. Natural TERE1 mutations associate with Schnyder's corneal dystrophy, characterized by lipid accumulation. TERE1 catalyzes menaquinone synthesis, known to affect cholesterol homeostasis. To explore this relationship, we altered TERE1 and TBL2 dosage via ectopic expression and interfering RNA and measured cholesterol by Amplex red. Protein interactions of wild-type and mutant TERE1 with GST-APOE were evaluated by binding assays and molecular modeling. We conducted a bladder tumor microarray TERE1 expression analysis and assayed tumorigenicity of J82 cells ectopically expressing TERE1. TERE1 expression was reduced in a third of invasive specimens. Ectopic TERE1 expression in J82 bladder cancer cells dramatically inhibited nude mouse tumorigenesis. TERE1 and TBL2 proteins inversely modulated cellular cholesterol in HEK293 and bladder cancer cells from 20% to 50%. TERE1 point mutations affected APOE interactions, and resulted in cholesterol levels that differed from wild type. Elevated tumor cell cholesterol is known to affect apoptosis and growth signaling; thus, loss of TERE1 in invasive bladder cancer may represent a defect in menaquinone-mediated cholesterol homeostasis that contributes to progression. C1 [Fredericks, William J.] Univ Penn, Dept Surg, Div Urol, VAMC Philadelphia, Philadelphia, PA 19104 USA. [McGarvey, Terry] Kirksville Osteopath Med Sch, Dept Anat, Kirksville, MO USA. [Lal, Priti; Puthiyaveettil, Raghunath; Tomaszewski, John; Sepulveda, Jorge] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Malkowicz, S. Bruce] Vet Affairs Med Ctr, Dept Surg Urol & Pathol, Philadelphia, PA USA. [Sepulveda, Jorge] Vet Affairs Med Ctr, Pathol Serv, Philadelphia, PA USA. [Labelle, Ed] Gloucester Cty Coll, Sewell, NJ USA. [Weiss, Jayne S.] Louisiana State Univ, Dept Ophthalmol, New Orleans, LA USA. [Weiss, Jayne S.] Louisiana State Univ, Ctr Eye, New Orleans, LA 70112 USA. [Nickerson, Michael L.] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. [Kruth, Howard S.] NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. [Brandt, Wolfgang; Wessjohann, Ludger A.] Leibniz Inst Plant Biochem, Halle, Germany. RP Fredericks, WJ (reprint author), Univ Penn, Dept Surg, Div Urol, VAMC Philadelphia, Univ & Woodland Ave,Room A418, Philadelphia, PA 19104 USA. EM william.fredericks@uphs.upenn.edu FU Veterans Affairs Merit Review; Veterans Affairs Medical Center Philadelphia FX We thank the Veterans Affairs Merit Review and the Veterans Affairs Medical Center Philadelphia for the grant support to S.B. Malkowicz. We thank the Innisfree Foundation of Bryn Mawr, PA, and The Castleman Family Fund for their generous support to S.B. Malkowicz and W.J. Fredericks. NR 92 TC 21 Z9 21 U1 1 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD NOV PY 2011 VL 30 IS 11 BP 851 EP 864 DI 10.1089/dna.2011.1315 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 843GW UT WOS:000296661300001 PM 21740188 ER PT J AU Stengel, A Tache, Y AF Stengel, Andreas Tache, Yvette TI Minireview: Nesfatin-1-An Emerging New Player in the Brain-Gut, Endocrine, and Metabolic Axis SO ENDOCRINOLOGY LA English DT Review ID SATIETY MOLECULE NESFATIN-1; PITUITARY-ADRENAL AXIS; CENTRAL-NERVOUS-SYSTEM; FOOD-INTAKE; PARAVENTRICULAR NUCLEUS; ARCUATE NUCLEUS; RAT-BRAIN; NEURONS; IMMUNOREACTIVITY; HYPOTHALAMUS AB Nesfatin-1 is a recently identified 82-amino-acid peptide derived from the precursor protein, nucleobindin2 (NUCB2). The brain distribution of NUCB2/nesfatin-1 at the mRNA and protein level along with functional studies in rodents support a role for NUCB2/nesfatin-1 as a novel satiety molecule acting through leptin-independent mechanisms. In addition, nesfatin-1 induces a wide spectrum of central actions to stimulate the pituitary-adrenal axis and sympathetic nervous system and influences visceral functions and emotion. These central actions combined with the activation of NUCB2/nesfatin-1 neurons in the brain by various stressors are indicative of a role in the adaptive response under stressful conditions. In the periphery, evidence is mounting that nesfatin-1 exerts a direct glucose-dependent insulinotropic action on beta-cells of the pancreatic islets. However, the cellular mechanisms of nesfatin-1's action remain poorly understood, partly because the receptor through which nesfatin-1 exerts its pleiotropic actions is yet to be identified. (Endocrinology 152: 4033-4038, 2011) C1 [Tache, Yvette] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Neurobiol Stress, Los Angeles, CA 90073 USA. [Stengel, Andreas; Tache, Yvette] Univ Calif Los Angeles, Dept Med, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress,Digest Dis Div, Los Angeles, CA 90024 USA. [Stengel, Andreas] Univ Med Berlin, Charite, Div Psychosomat Med & Psychotherapy, Dept Med, D-10117 Berlin, Germany. RP Tache, Y (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Neurobiol Stress, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU National Institutes of Health (NIH) [R01 DK-33061]; NIH Center [DK-41301 (Animal Core)]; Veterans Affairs Research Career Scientist grant FX This work was supported by National Institutes of Health (NIH) R01 DK-33061, NIH Center Grant DK-41301 (Animal Core), and a Veterans Affairs Research Career Scientist grant (to Y.T.). NR 58 TC 41 Z9 43 U1 2 U2 12 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2011 VL 152 IS 11 BP 4033 EP 4038 DI 10.1210/en.2011-1500 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 842GR UT WOS:000296583900007 PM 21862618 ER PT J AU Schirmer, P Winters, M Holodniy, M AF Schirmer, P. Winters, M. Holodniy, M. TI HIV-HBV vaccine escape mutant infection with loss of HBV surface antibody and persistent HBV viremia on tenofovir/emtricitabine without antiviral resistance SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE HIV; HBV; Vaccine escape; Tenofovir; Emtricitabine ID HEPATITIS-B; COINFECTION; ANTIGEN; CARRIER AB We report a case of acute hepatitis B virus genotype A vaccine escape mutant infection with loss of HBV vaccine-induced seropositivity in a HIV-1 infected patient. His HBV is unresponsive to tenofovir/emtricitabine treatment demonstrated by persistent viremia despite lacking known resistance mutations and while having an undetectable HIV-1 viral load. Published by Elsevier B. V. C1 [Schirmer, P.; Holodniy, M.] US Dept Vet Affairs, Off Publ Hlth, Palo Alto, CA 94304 USA. [Winters, M.; Holodniy, M.] Stanford Univ, Palo Alto, CA 94304 USA. RP Schirmer, P (reprint author), US Dept Vet Affairs, Off Publ Hlth Surveillance & Res, 3801 Miranda Ave,132, Palo Alto, CA 94304 USA. EM patricia.schirmer@va.gov FU Department of Veterans Affairs [HOM0055] FX This work was supported by a Department of Veterans Affairs grant [HOM0055] to Mark Holodniy. NR 14 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD NOV PY 2011 VL 52 IS 3 BP 261 EP 264 DI 10.1016/j.jcv.2011.07.014 PG 4 WC Virology SC Virology GA 842AF UT WOS:000296556800021 PM 21840252 ER PT J AU McMillan, PJ Kraemer, BC Robinson, L Leverenz, JB Raskind, M Schellenberg, G AF McMillan, Pamela J. Kraemer, Brian C. Robinson, Linda Leverenz, James B. Raskind, Murray Schellenberg, Gerard TI Truncation of tau at E391 Promotes Early Pathologic Changes in Transgenic Mice SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Aggregation; Alzheimer disease; Tau; Transgenic mice; Truncation ID PAIRED HELICAL FILAMENTS; INDUCIBLE MOUSE MODELS; RAT DENTATE GYRUS; ALZHEIMERS-DISEASE; PROTEIN-TAU; NEURODEGENERATIVE DISORDERS; NEUROFIBRILLARY PATHOLOGY; DETERMINES AGGREGATION; NERVOUS-SYSTEM; TAUOPATHY AB Proteolytic cleavage of tau at glutamic acid 391 (E391) is linked to the pathogenesis of Alzheimer disease (AD). This C-terminal-truncated tau species exists in neurofibrillary tangles and abnormal neurites in the brains of AD patients and may potentiate tau polymerization. We generated a mouse model that expresses human tau truncated at E391 to begin to elucidate the role of this C-terminal-truncated tau species in the development of tau pathology. Our results show that truncated but otherwise wild-type human tau is sufficient to drive pretangle pathologic changes in tau, including accumulation of insoluble tau, somatodendritic redistribution, formation of pathologic conformations, and dual phosphorylation of tau at sites associated with AD pathology. In addition, these mice exhibit atypical neuritic tau immunoreactivity, including abnormal neuritic processes and dystrophic neurites. These results suggest that changes in tau proteolysis can initiate tauopathy. C1 [McMillan, Pamela J.; Leverenz, James B.; Raskind, Murray] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Kraemer, Brian C.; Robinson, Linda] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [McMillan, Pamela J.; Leverenz, James B.; Raskind, Murray] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Kraemer, Brian C.] Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98195 USA. [Leverenz, James B.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Schellenberg, Gerard] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP McMillan, PJ (reprint author), Seattle Vet Affairs Puget Sound Hlth Care Syst, Box 358280,S182 GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM pammcm@u.washington.edu FU National Institute on Aging [AG17586, 2P50AG005136-27]; Department of Veterans Affairs; Veterans Affairs National Institute of Neurological Disorders and Stroke [5P50NS062684-02] FX This work was supported by National Institute on Aging Grant AG17586 to G.D.S., Department of Veterans Affairs Merit Review Grant to B.C.K., and Veterans Affairs National Institute of Neurological Disorders and Stroke 5P50NS062684-02 and National Institute on Aging 2P50AG005136-27 to J.B.L. NR 53 TC 14 Z9 15 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD NOV PY 2011 VL 70 IS 11 BP 1006 EP 1019 DI 10.1097/NEN.0b013e31823557fb PG 14 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 842DB UT WOS:000296567800006 PM 22002427 ER PT J AU Stark, S Snetselaar, L Piraino, B Stone, RA Kim, S Hall, B Burke, LE Sevick, MA AF Stark, Susan Snetselaar, Linda Piraino, Beth Stone, Roslyn A. Kim, Sunghee Hall, Beth Burke, Lora E. Sevick, Mary Ann TI Personal Digital Assistant-Based Self-Monitoring Adherence Rates in 2 Dialysis Dietary Intervention Pilot Studies: BalanceWise-HD and BalanceWise-PD SO JOURNAL OF RENAL NUTRITION LA English DT Article ID HOME-BASED WALKING; WEIGHT-LOSS; PROGRAM AB Objective: The dialysis dietary regimen is complicated, and computer-based dietary self-monitoring may be useful for helping dialysis patients manage their dietary regimen. In this report, we describe dietary self-monitoring rates among study participants randomized to the intervention arms of 2 pilot studies. Methods: Both studies tested similar interventions involving dietary counseling paired with personal digital assistant-based self-monitoring. One study was performed in hemodialysis (HD) and one in peritoneal dialysis (PD) patients. Results: HD intervention participants entered an average of 244.9 meals (median = 288; interquartile range [IQR]: 186 to 342) over the 16-week intervention, 2.2 meals per day (median = 2.6; IQR: 1.7 to 3.1), and 73% of expected meals (median = 86; IQR: 55 to 102), assuming intake of 3 meals per day. At least some meals were entered in 87% of the observed weeks (median = 100%; IQR: 81 to 100). PD intervention participants entered an average of 212.1 meals (median = 203; IQR: 110 to 312) over the 16-week intervention, 1.9 meals per day (median = 1.8; IQR: 1 to 2.8), and 63% of expected meals (median = 60; IQR: 33 to 93), assuming 3 meals per day. At least some meals were entered in 80% of the observed weeks (median = 94; IQR: 50 to 100). Conclusion: These HD and PD patients demonstrated excellent rates of self-monitoring. Additional research with a larger sample is required to confirm these findings. (C) 2011 by the National Kidney Foundation, Inc. All rights reserved. C1 [Stark, Susan] Univ Pittsburgh, Sch Med, Dept Med, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. [Snetselaar, Linda] Univ Iowa, Coll Publ Hlth, Dept Endocrinol, Iowa City, IA USA. [Stone, Roslyn A.; Kim, Sunghee; Burke, Lora E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Stone, Roslyn A.; Kim, Sunghee; Sevick, Mary Ann] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Burke, Lora E.] Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, Pittsburgh, PA 15261 USA. [Piraino, Beth] Univ Pittsburgh, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Burke, Lora E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Sevick, Mary Ann] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA. [Sevick, Mary Ann] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Stark, S (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Ctr Res Hlth Care, 3520 Forbes Ave,1st Floor, Pittsburgh, PA 15213 USA. EM starsa2@upmc.edu OI Piraino, Beth/0000-0001-5061-0841 FU Paul Teschan Research Foundation; [NIH/NIDDK/DK-R21DK067181]; [NIH/NCRR/CTSA-UL1-RR024153]; [NIH/NCRR/GCRC-M01- RR000056] FX The work in this article was supported by the following grants: Paul Teschan Research Foundation, NIH/NIDDK/DK-R21DK067181, NIH/NCRR/CTSA-UL1-RR024153, and NIH/NCRR/GCRC-M01- RR000056. The authors take full responsibility for the contents of this article, which do not represent the views of the Department of Veterans Affairs or the United States Government. The authors acknowledge the individual contributions of: Rita Marsh, RN, MSN; Deborah Klinvex, BA; and Tienna Luster. NR 18 TC 4 Z9 4 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1051-2276 J9 J RENAL NUTR JI J. Renal Nutr. PD NOV PY 2011 VL 21 IS 6 BP 492 EP 498 DI 10.1053/j.jrn.2010.10.026 PG 7 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA 841SJ UT WOS:000296533100009 PM 21420316 ER PT J AU Marshall, CL Balentine, CJ Robinson, CN Wilks, JA Anaya, D Artinyan, A Awad, SS Berger, DH Albo, D AF Marshall, Christy L. Balentine, Courtney J. Robinson, Celia N. Wilks, Jonathan A. Anaya, Daniel Artinyan, Avo Awad, Samir S. Berger, David H. Albo, Daniel TI A Multidisciplinary Cancer Center Maximizes Surgeons' Impact SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE colorectal cancer center; specialty-trained surgeons; prognostic; outcomes; colorectal cancer ID COLORECTAL LIVER METASTASES; HOSPITAL PROCEDURE VOLUME; COLON-CANCER; RECTAL-CANCER; COMBINED RESECTION/ABLATION; RADIOFREQUENCY ABLATION; SURGICAL SPECIALITY; HEPATIC RESECTION; OUTCOMES; RECURRENCE AB Background. Colorectal cancer patients require care across different disciplines. Integration of multidisciplinary care is critical to accomplish excellent oncologic results. We hypothesized that the establishment of a dedicated colorectal cancer center (CRCC) around specialty-trained surgeons will lead to increased multidisciplinary management and improved outcomes in colorectal cancer patients. Methods. We analyzed data from three periods: a baseline group, a period after the recruitment of specialty-trained surgeons, and a period after the creation of a dedicated multidisciplinary cancer center. Data analyzed included surrogate markers of surgical oncologic care, multidisciplinary integration, and oncologic outcomes. Results. Recruitment of specialized surgeons led to improvements in surgical oncologic care; the establishment of the CRCC resulted in further improvements in surgical oncologic care and multidisciplinary integration. Conclusion. Our study suggests that although the recruitment of specialty-trained surgeons in a high volume center leads to improvement in surgical oncologic care, it is the establishment of a multidisciplinary center around the surgeons that leads to integrated care and improvements in oncologic outcomes. (C) 2011 Elsevier Inc. All rights reserved. C1 [Albo, Daniel] Baylor Coll Med, Div Surg Oncol, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. Baylor Coll Med, Dept Surg, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Albo, D (reprint author), Baylor Coll Med, Div Surg Oncol, Michael E DeBakey Dept Surg, 1709 Dryden,Suite 1500, Houston, TX 77030 USA. EM dalbo@bcm.edu NR 29 TC 4 Z9 4 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD NOV PY 2011 VL 171 IS 1 BP 15 EP 22 DI 10.1016/j.jss.2010.12.007 PG 8 WC Surgery SC Surgery GA 839LS UT WOS:000296368000022 PM 21696763 ER PT J AU Angel, LF Tapson, V Galgon, RE Restrepo, MI Kaufman, J AF Angel, Luis F. Tapson, Victor Galgon, Richard E. Restrepo, Marcos I. Kaufman, John TI Systematic Review of the Use of Retrievable Inferior Vena Cava Filters SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review ID DEEP-VEIN THROMBOSIS; PULMONARY-EMBOLISM; VENOUS THROMBOEMBOLISM; LONG-TERM; FOLLOW-UP; CLINICAL-EXPERIENCE; TECHNICAL SUCCESS; TRAUMA PATIENTS; OPTEASE FILTER; MULTICENTER AB Purpose: To review the available literature on retrievable inferior vena cava (IVC) filters to examine the effectiveness and risks of these devices. Materials and Methods: Investigators searched MEDLINE for clinical trials evaluating retrievable filters and reviewed the complications reported to the Manufacturer and User Facility Device Experience (MAUDE) database of the U.S. Food and Drug Administration (FDA). Results: Eligibility criteria were met by 37 studies comprising 6,834 patients. All of the trials had limitations, and no studies were randomized. There were 11 prospective clinical trials; the rest were retrospective studies. Despite the limitations of the evidence, the IVC filters seemed to be effective in preventing pulmonary embolism (PE); the rate of PE after IVC placement was 1.7%. The mean retrieval rate was 34%. Most of the filters became permanent devices. Multiple complications associated with the use of IVC filters were described in the reviewed literature or were reported to the MAUDE database; most of these were associated with long-term use (> 30 days). At the present time, the objective comparison data of different filter designs do not support superiority of any particular design. Conclusions: In high-risk patients for whom anticoagulation is not feasible, retrievable IVC filters seem to be effective in preventing PE. Long-term complications are a serious concern with the use of these filters. The evidence of the effectiveness and the risks was limited by the small number of prospective studies. C1 [Angel, Luis F.; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA. [Tapson, Victor] Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC USA. [Galgon, Richard E.] Univ Wisconsin, Dept Anesthesiol, Madison, WI USA. [Restrepo, Marcos I.] S Texas Vet Hlth Care Syst, VERDICT, Audie L Murphy Div, San Antonio, TX USA. [Kaufman, John] Oregon Hlth & Sci Ctr, Dotter Intervent Inst, Portland, OR USA. RP Angel, LF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM angel@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 FU Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Texas Health Science Center at San Antonio; BiO2 Medical FX Funding was provided by the Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Texas Health Science Center at San Antonio.; L.F.A. has a financial relationship with BiO2 Medical. J.K. has received research funding from BiO2 Medical. None of the other authors have identified a conflict of interest. NR 66 TC 105 Z9 107 U1 3 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD NOV PY 2011 VL 22 IS 11 BP 1522 EP 1530 DI 10.1016/j.jvir.2011.08.024 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 843HB UT WOS:000296661800006 PM 22024114 ER PT J AU Muir, ER Duong, TQ AF Muir, Eric R. Duong, Timothy Q. TI Layer-Specific Functional and Anatomical MRI of the Retina With Passband Balanced SSFP SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE steady state free precession; SSFP; fMRI; retina; ophthalmology; hypoxia ID MANGANESE-ENHANCED MRI; CHOROIDAL BLOOD-FLOW; RAT RETINA; DEGENERATION; RESOLUTION; BRAIN; TESLA AB The retina consists of multiple cellular and synaptic layers and is nourished by two distinct (retinal and choroidal) circulations bounding the retina, separated by an avascular layer. High spatiotemporal resolution, layer-specific MRI of the retina remains challenging due to magnetic inhomogeneity-induced artifacts. This study reports passband balanced steady-state free-precession (bSSFP) MRI at 45x45x500 mm and 1.6 s temporal resolution to image the mouse retina, overcoming geometric distortion and signal dropout while maintaining rapid acquisition and high signal-to-noise ratio. bSSFP images revealed multiple alternating dark-bright-dark-bright retinal layers. Hypoxic (10% O(2)) inhalation decreased bSSFP signals in the two layers bounding the retina, corresponding to the retinal and choroidal vasculatures. The layer in between showed no substantial response and was assigned the avascular photoreceptor layers. Choroidal responses (-25.9 +/- 6.4%, mean +/- SD, n=6) were significantly (P< 0.05) larger than retinal vascular responses (-11.6 +/- 2.4%). bSSFP offers very high spatiotemporal resolution and could have important applications in imaging layer-specific changes in retinal diseases. Magn Reson Med 66: 1416-1421, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Muir, Eric R.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, San Antonio, TX 78229 USA. [Muir, Eric R.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Radiol, San Antonio, TX 78229 USA. [Muir, Eric R.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Physiol, San Antonio, TX 78229 USA. [Muir, Eric R.] Georgia Inst Technol, Dept Biomed Engn, Atlanta, GA 30332 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, Dept Ophthalmol, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008; Muir, Eric/H-8830-2013 FU National Eye Institute/National Institutes of Health [R01 EY018855, R01 EY014211]; Department of Veterans Affairs FX Grant sponsor: National Eye Institute/National Institutes of Health; Grant numbers: R01 EY018855, R01 EY014211; Grant sponsor: Department of Veterans Affairs (VA MERIT Award). NR 27 TC 16 Z9 16 U1 0 U2 0 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 NOV PY 2011 VL 66 IS 5 BP 1416 EP 1421 DI 10.1002/mrm.22935 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 839SP UT WOS:000296389800024 PM 21604296 ER PT J AU Middleton, LE Grinberg, LT Miller, B Kawas, C Yaffe, K AF Middleton, L. E. Grinberg, L. T. Miller, B. Kawas, C. Yaffe, K. TI Neuropathologic features associated with Alzheimer disease diagnosis Age matters SO NEUROLOGY LA English DT Article ID CENTER NACC DATABASE; OLDEST-OLD; LEWY BODIES; DEMENTIA; CENTENARIANS; POPULATION; NONAGENARIANS; PREVALENCE; AUTOPSY; COHORT AB Objective: To examine whether the association between clinical Alzheimer disease (AD) diagnosis and neuropathology and the precision by which neuropathology differentiates people with clinical AD from those with normal cognition varies by age. Methods: We conducted a cross-sectional analysis of 2,014 older adults (>= 70 years at death) from the National Alzheimer's Coordinating Center database with clinical diagnosis of normal cognition (made <= 1 year before death, n = 419) or AD (at >= 65 years, n = 1,595) and a postmortem neuropathologic examination evaluating AD pathology (neurofibrillary tangles, neuritic plaques) and non-AD pathology (diffuse plaques, amyloid angiopathy, Lewy bodies, macrovascular disease, microvascular disease). We used adjusted logistic regression to analyze the relationship between clinical AD diagnosis and neuropathologic features, area under the receiver operating characteristic curve (c statistic) to evaluate how precisely neuropathology differentiates between cognitive diagnoses, and an interaction to identify effect modification by age group. Results: In a model controlling for coexisting neuropathologic features, the relationship between clinical AD diagnosis and neurofibrillary tangles was significantly weaker with increasing age (p < 0.001 for interaction). The aggregate of all neuropathologic features more strongly differentiated people with clinical AD from those without in younger age groups (70-74 years: c statistic, 95% confidence interval: 0.93, 0.89-0.96; 75-84 years: 0.95, 0.87-0.95; >= 85 years: 0.83, 0.80-0.87). Non-AD pathology significantly improved precision of differentiation across all age groups (p < 0.004). Conclusion: Clinical AD diagnosis was more weakly associated with neurofibrillary tangles among the oldest old compared to younger age groups, possibly due to less accurate clinical diagnosis, better neurocompensation, or unaccounted pathology among the oldest old. Neurology (R) 2011;77:1737-1744 C1 [Middleton, L. E.] Univ Waterloo, Waterloo, ON N2L 3G1, Canada. [Middleton, L. E.] Sunnybrook Hlth Sci Ctr, Heart & Stroke Fdn, Ctr Stroke Recovery, Toronto, ON M4N 3M5, Canada. [Miller, B.; Yaffe, K.] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Grinberg, L. T.; Miller, B.; Yaffe, K.] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, K.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Middleton, LE (reprint author), 200 Univ Ave W,BMH 1114, Waterloo, ON N2L 3G1, Canada. EM laura.middleton@uwaterloo.ca RI Middleton, Laura/C-6024-2009 OI Middleton, Laura/0000-0001-8624-3123; grinberg, lea/0000-0002-6809-0618 FU Canadian Institute of Health Research; Alzheimer's Association; John Douglas French Alzheimer's Foundation; publication of Behavioral Neurology of Dementia (Cambridge); Handbook of Neurology (Elsevier); Human Frontal Lobes (Guilford); Novartis; NIH/NIA; State of California Alzheimer's Center; NIH/ Alzheimer's Disease Research Centre; NIH (NIA, NIDDK, NIMH); Department of Defense; American Health Assistance Foundation; Anonymous Foundation; Alzheimer Association; NIH [U01 AG016976] FX Dr. Middleton serves on the editorial board of the Journal of Alzheimer's Disease and receives fellowship support from the Canadian Institute of Health Research fellowship. Dr. Grinberg serves as an Associate Editor for Frontiers in Dementia and Cell and Tissue Banking; and receives research support from the Alzheimer's Association and the John Douglas French Alzheimer's Foundation. Dr. Miller serves on a scientific advisory board for the Alzheimer's Disease Clinical Study; serves as an Editor for Neurocase and as an Associate Editor of ADAD; receives royalties from the publication of Behavioral Neurology of Dementia (Cambridge, 2009), Handbook of Neurology (Elsevier, 2009), and The Human Frontal Lobes (Guilford, 2008); serves as a consultant for Lundbeck Inc., Elan Corporation, and Allon Therapeutics, Inc.; serves on speakers' bureaus for Novartis and Pfizer Inc.; and receives research support from Novartis and the NIH/NIA and the State of California Alzheimer's Center. Dr. Kawas serves on a scientific advisory board for Quintiles and receives research support from the NIH/ Alzheimer's Disease Research Centre. Dr. Yaffe has served on data safety monitoring boards for Pfizer Inc, Medivation, Inc., and the NIH (NIMH and NIA trials); and has received research support from the NIH (NIA, NIDDK, NIMH), the Department of Defense, American Health Assistance Foundation, Anonymous Foundation, and the Alzheimer Association.; The National Alzheimer's Coordinating Centre is funded by NIH U01 AG016976. The NIA approved the final manuscript but did not influence the analysis, results, or interpretation. NR 31 TC 24 Z9 24 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 2011 VL 77 IS 19 BP 1737 EP 1744 DI 10.1212/WNL.0b013e318236f0cf PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 844SO UT WOS:000296767800010 PM 22031532 ER PT J AU Lee, J Ferrucci, S AF Lee, Jimin Ferrucci, Steven TI Peripapillary subretinal neovascular membranes: A review SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION LA English DT Review DE Peripapillary subretinal neovascularization; Juxtapapillary subretinal neovascularization; Age-related macular degeneration; Choroidal neovascular membrane ID POLYPOIDAL CHOROIDAL VASCULOPATHY; INTRAVITREAL BEVACIZUMAB; LASER PHOTOCOAGULATION; OCULAR HISTOPLASMOSIS; PHOTODYNAMIC THERAPY; SURGICAL-TREATMENT; NATURAL-HISTORY; VERTEPORFIN; SURGERY; REMOVAL AB Peripapillary subretinal neovascular membranes (PSRNVM) are most commonly associated with age-related macular degeneration and idiopathic causes in older patients. In younger patients, the condition has been linked to a wide variety of other conditions. As with the more commonly occurring macular form of choroidal neovascular membranes, PSRNVM can also lead to severe vision loss. Therefore, clinicians must take care to avoid overlooking this event to provide appropriate management and treatment. Current knowledge of PSRNVM suggests the importance of regular examinations of the affected eye in both treated and untreated cases to watch for progression and recurrence, which are unpredictable, and also of the fellow eye because there is a high risk of bilateral involvement. Optometry 2011;82:681-688 C1 [Lee, Jimin; Ferrucci, Steven] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lee, Jimin; Ferrucci, Steven] Sepulveda Vet Affairs Ambulatory Care Ctr Nursing, Sepulveda, CA USA. [Ferrucci, Steven] So Calif Coll Optometry, Fullerton, CA USA. RP Ferrucci, S (reprint author), Sepulveda Vet Affairs Ambulatory Care Ctr, Dept Optometry, 16111 Plummer St 112E, Sepulveda, CA 91343 USA. EM steven.ferrucci@va.gov NR 32 TC 1 Z9 1 U1 2 U2 6 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 NOV PY 2011 VL 82 IS 11 BP 681 EP 688 DI 10.1016/j.optm.2011.04.104 PG 8 WC Ophthalmology SC Ophthalmology GA 843QL UT WOS:000296687200006 PM 21873121 ER PT J AU Mareninova, OA Yakubov, I Gukovsky, I Gukovskaya, AS AF Mareninova, O. A. Yakubov, I. Gukovsky, I. Gukovskaya, A. S. TI Lysosomal Dysfunction in Pancreatitis SO PANCREAS LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2011 VL 40 IS 8 BP 1337 EP 1337 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 839VQ UT WOS:000296398000155 ER PT J AU Carpenter, LL Tyrka, AR Lee, JK Tracy, AP Wilkinson, CW Price, LH AF Carpenter, Linda L. Tyrka, Audrey R. Lee, Janet K. Tracy, Aaron P. Wilkinson, Charles W. Price, Lawrence H. TI A placebo-controlled study of sertraline's effect on cortisol response to the dexamethasone/corticotropin-releasing hormone test in healthy adults SO PSYCHOPHARMACOLOGY LA English DT Article DE Sertraline; Dex/CRH test; Cortisol; HPA axis ID PITUITARY-ADRENAL-SYSTEM; MAJOR DEPRESSIVE EPISODE; HPA-AXIS REACTIVITY; CHILDHOOD TRAUMA; DEX/CRH TEST; ANTIDEPRESSANT TREATMENT; LITHIUM AUGMENTATION; UNIPOLAR DEPRESSION; AFFECTIVE-DISORDERS; ACTH RESPONSES AB Rationale The dexamethasone/corticotropin-releasing hormone (Dex/CRH) test is a neuroendocrine probe involving serial blood sampling of cortisol during a standardized pharmacological challenge without inducing psychological distress in humans. Some past studies in depressed patients have shown a "normalization" or decrease in cortisol response to the Dex/CRH test following successful treatment with an antidepressant. Studies in nondepressed healthy adult samples have also shown aberrant cortisol reactivity to be associated with depression risk factors. These findings prompted research into the use of the Dex/CRH test as a tool for developing antidepressant drugs. Objectives In this study, the Dex/CRH test was evaluated with regard to its potential utility for drug development in nonclinical samples. Methods The Dex/CRH test was administered before and after 6 weeks of blinded treatment with either sertraline 100 mg/day or matching placebo in 22 healthy adults ( 13 women, nine men). Results Cortisol response to the Dex/CRH test increased following treatment with standard doses of sertraline, compared to placebo, after controlling for age and sex. Conclusions The observed pattern of change contrasts with results from published studies in depressed patients and with our initial hypothesis. C1 [Carpenter, Linda L.; Tyrka, Audrey R.; Lee, Janet K.; Tracy, Aaron P.; Price, Lawrence H.] Butler Hosp, Mood Disorders Res Program, Providence, RI 02906 USA. [Carpenter, Linda L.; Tyrka, Audrey R.; Lee, Janet K.; Tracy, Aaron P.; Price, Lawrence H.] Butler Hosp, Lab Clin Neurosci, Brown Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Wilkinson, Charles W.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Wilkinson, Charles W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. RP Carpenter, LL (reprint author), Butler Hosp, Mood Disorders Res Program, 345 Blackstone Blvd, Providence, RI 02906 USA. EM Linda_Carpenter_MD@brown.edu RI Tyrka, Audrey/L-2504-2014 FU Pfizer Inc.; Department of Veterans Affairs FX The authors thank Kelly Colombo, B. A. for her assistance with data management, Ashley Clement for her research assistant support in manuscript preparation, and Daniel Gonzalez for performance of the cortisol assays. This work was supported by an investigator-initiated grant from Pfizer Inc. (LLC) and by the Department of Veterans Affairs (CWW). NR 63 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2011 VL 218 IS 2 BP 371 EP 379 DI 10.1007/s00213-011-2336-y PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 844EL UT WOS:000296730400007 PM 21617914 ER PT J AU Krueger, PM Saint Onge, JM Chang, VW AF Krueger, Patrick M. Saint Onge, Jarron M. Chang, Virginia W. TI Race/ethnic differences in adult mortality: The role of perceived stress and health behaviors SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Race; Ethnicity; Mortality; Health behaviors; Stress; USA ID UNITED-STATES; SOCIOECONOMIC-STATUS; RACIAL DISPARITIES; ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; SLEEP DURATION; BLACK; WHITE; RISK AB We examine the role of perceived stress and health behaviors (i.e., cigarette smoking, alcohol consumption, physical inactivity, sleep duration) in shaping differential mortality among whites, blacks, and Hispanics. We use data from the 1990 National Health Interview Survey (N = 38,891), a nationally representative sample of United States adults, to model prospective mortality through 2006. Our first aim examines whether unhealthy behaviors and perceived stress mediate race/ethnic disparities in mortality. The black disadvantage in mortality, relative to whites, closes after adjusting for socioeconomic status (SES), but re-emerges after adjusting for the lower smoking levels among blacks. After adjusting for SES. Hispanics have slightly lower mortality than whites; that advantage increases after adjusting for the greater physical inactivity among Hispanics, but closes after adjusting for their lower smoking levels. Perceived stress, sleep duration, and alcohol consumption do not mediate race/ethnic disparities in mortality. Our second aim tests competing hypotheses about race/ethnic differences in the relationships among unhealthy behaviors, perceived stress, and mortality. The social vulnerability hypothesis predicts that unhealthy behaviors and high stress levels will be more harmful for race/ethnic minorities. In contrast, the Blaxter (1990) hypothesis predicts that unhealthy lifestyles will be less harmful for disadvantaged groups. Consistent with the social vulnerability perspective, smoking is more harmful for blacks than for whites. But consistent with the Blaxter hypothesis, compared to whites, current smoking has a weaker relationship with mortality for Hispanics, and low or high levels of alcohol consumption, high levels of physical inactivity, and short or long sleep hours have weaker relationships with mortality for blacks. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Krueger, Patrick M.] Univ Colorado Denver, Denver, CO USA. [Krueger, Patrick M.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Saint Onge, Jarron M.] Univ Houston, Dept Sociol, Houston, TX USA. [Chang, Virginia W.] Philadelphia VAMC, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Chang, Virginia W.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Chang, Virginia W.] Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. RP Krueger, PM (reprint author), Univ Colorado Denver, Denver, CO USA. EM Patrick.Krueger@ucdenver.edu OI Saint Onge, Jarron/0000-0002-0914-4882 FU University of Colorado [NICHD R21 HD51146]; University of Houston [NIDA R24 DA019798]; National Institutes of Health [NICHD K12-HD043459] FX This paper has benefited from presentation at the 2008 meetings of the American Sociological Association in Boston, MA. We acknowledge administrative support from the University of Colorado Population Program (NICHD R21 HD51146), the University of Houston (NIDA R24 DA019798), and the Leonard Davis Institute of Health Economics at the University of Pennsylvania, and research support from the National Institutes of Health (NICHD K12-HD043459). NR 52 TC 18 Z9 18 U1 2 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD NOV PY 2011 VL 73 IS 9 BP 1312 EP 1322 DI 10.1016/j.socscimed.2011.08.007 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 843OF UT WOS:000296680800005 PM 21920655 ER PT J AU Nelson, P Young, HN Knobloch, MJ Griesbach, SA AF Nelson, Philip Young, Henry N. Knobloch, Mary Jo Griesbach, Sara A. TI Telephonic Monitoring and Optimization of Inhaler Technique SO TELEMEDICINE AND E-HEALTH LA English DT Article DE asthma; asthma management; telephonic monitoring; inhaler; metered-dose inhalers; MDI; diskus; dry powder inhalers,patient education as topic; telemedicine ID METERED-DOSE INHALER; RANDOMIZED CONTROLLED-TRIAL; INHALATION TECHNIQUE; ASTHMA REVIEWS; CARE; ACCESSIBILITY; INSTRUCTION; MISUSE AB Introduction: Improper inhaler technique is a common problem affecting asthma control and healthcare costs. Telephonic asthma management can increase access to care while reducing costs and hospitalizations. However, no reliable method has been established for telephonically evaluating and correcting inhaler technique. Objective: The purpose of this study was to pilot test a method for assessing and correcting patient inhaler technique via telephone. Methods: Participants (n = 30) were adults with asthma using metered-dose inhalers (MDIs) and diskus inhalers. A pharmacist was located in one room and communicated via telephone with a participant in another room. The pharmacist telephonically assessed and taught inhaler technique. Participants were videorecorded, and videos were later examined by a second pharmacist to visually evaluate inhaler technique. Participants were assigned pre- and posteducation inhaler technique scores for the telephonic and video assessments. Scores were based on summated scales for MDI (0-9) and diskus (0-11) inhalers. Paired samples t-tests were used to compare telephone and video assessments. Results: Findings indicated a significant difference between the telephone and video assessments of MDI technique (p < 0.05); however, no difference was found for the diskus inhaler. Comparing pre-and posteducation inhaler technique for MDI and diskus, mean scores significantly improved from 5.7 to 7.8 (p < 0.05) and from 8.5 to 10.4 (p < 0.05), respectively. Conclusions: The telephonic method was able to improve and detect some deficiencies in patients' inhaler technique. However, modifications and further investigation will more clearly determine the role and value of such a telephonic intervention. C1 [Knobloch, Mary Jo; Griesbach, Sara A.] Marshfield Clin Fdn Med Res & Educ, Div Educ, Marshfield, WI 54449 USA. [Nelson, Philip] S Texas Vet Hlth Care Syst, Ambulatory Care Pharm, San Antonio, TX USA. [Young, Henry N.] Univ Wisconsin, Social & Adm Sci Div, Madison Sch Pharm, Sonderegger Res Ctr, Madison, WI USA. [Knobloch, Mary Jo] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Partnership Program, Madison, WI USA. RP Griesbach, SA (reprint author), Marshfield Clin Fdn Med Res & Educ, Div Educ, 1000 N Oak Ave,GQ4, Marshfield, WI 54449 USA. EM griesbach.sara@marshfieldclinic.org FU Marshfield Clinic's Division of Education; National Center for Research Resources, National Institutes of Health [1UL1RR025011] FX The authors are grateful to Andrea Mahnke, BIRC usability analyst, for the wonderful technical support in utilizing the Marshfield Clinic Research Foundation's BIRC lab. We also thank Nina M. Antoniotti, RN, MBA, PhD; Elizabeth D. Cox, MD, PhD; and Megan A. Moreno, MD, MSEd, MPH, for their review of the article. We further thank Marie Fleisner of the Marshfield Clinic Research Foundation's Office of Scientific Publication for editorial assistance in the preparation of this article. Funding for this study was provided by Marshfield Clinic's Division of Education Resident Research Program and supported by grant 1UL1RR025011 from the Clinical and Translational Science Award program of the National Center for Research Resources, National Institutes of Health. NR 33 TC 8 Z9 8 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED E-HEALTH JI Telemed. e-Health PD NOV PY 2011 VL 17 IS 9 BP 734 EP 740 DI 10.1089/tmj.2011.0047 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 842HT UT WOS:000296588400012 PM 21943162 ER PT J AU Cristini, S Alessandri, G Acerbi, F Ciusani, E Colombo, A Fascio, U Nicosia, RF Invernizzi, RW Gelati, M Parati, EA Invernici, G AF Cristini, Silvia Alessandri, Giulio Acerbi, Francesco Ciusani, Emilio Colombo, Augusto Fascio, Umberto Nicosia, Roberto F. Invernizzi, Roberto W. Gelati, Maurizio Parati, Eugenio A. Invernici, Gloria TI Three-Dimensional Self-Organizing Neural Architectures: A Neural Stem Cells Reservoir and a System for Neurodevelopmental Studies SO TISSUE ENGINEERING PART C-METHODS LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; ADULT HUMAN BRAIN; PROGENITOR CELLS; IN-VITRO; NEURONAL PROGENITORS; RECEPTOR ACTIVATION; GENE-EXPRESSION; PRECURSOR CELLS; SPINAL-CORD AB Complex microenvironmental stimuli influence neural cell properties. To study this, we developed a three-dimensional (3-D) neural culture system, composed of different populations including neurons, astrocytes, and neural stem cells (NSCs). In particular, these last-mentioned cells represent a source potentially exploitable to test drugs, to study neurodevelopment and cell-therapies for neuroregenerations. On seeding on matrigel in a medium supplemented with serum and mitogens, cells obtained from human fetal brain tissue formed 3-D self-organizing neural architectures. Immunocytochemical analysis demonstrated the presence of undifferentiated nestin + and CD133+ cells, surrounded by beta-tub-III+ and GFAP + cells, suggesting the formation of niches containing potential human NSCs (hNSCs). The presence of hNSCs was confirmed by both neurosphere assay and RT-PCR, and their multipotentiality was demonstrated by both immunofluorescent staining and RT-PCR. Flow cytometry analysis revealed that neurosphere forming cells originating from at least two different subsets expressing, respectively, CD133 and CD146 markers were endowed with different proliferative and differentiation potential. Our data implicate that the complexity of environment within niches and aggregates of heterogeneous neural cell subsets may represent an innovative platform for neurobiological and neurodevelopmental investigations and a reservoir for a rapid expansion of hNSCs. C1 [Cristini, Silvia; Alessandri, Giulio; Gelati, Maurizio; Parati, Eugenio A.; Invernici, Gloria] Fdn IRCCS Ist Neurol Carlo Besta, Lab Cellular Neurobiol, I-20133 Milan, Italy. [Acerbi, Francesco] Fdn IRCCS Ist Neurol Carlo Besta, Dept Neurosurg, I-20133 Milan, Italy. [Acerbi, Francesco] Univ Milan, Dept Neurol Sci, Milan, Italy. [Ciusani, Emilio] Fdn IRCCS Ist Neurol Carlo Besta, Lab Clin Anal, I-20133 Milan, Italy. [Colombo, Augusto] Fdn IRCCS Osped Maggiore Policlin Mangiagalli & R, Dept Obstet & Gynecol, Milan, Italy. [Fascio, Umberto] Univ Milan, Interdept Ctr Adv Microscopy CIMA, Milan, Italy. [Nicosia, Roberto F.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Nicosia, Roberto F.] Univ Washington, Seattle, WA 98195 USA. [Invernizzi, Roberto W.] Ist Ric Farmacol M Negri, Lab Neurochem & Behav, Milan, Italy. RP Invernici, G (reprint author), Fdn IRCCS Ist Neurol Carlo Besta, Lab Cellular Neurobiol, Via Celoria 11, I-20133 Milan, Italy. EM gloria.invernici@istituto-besta.it RI Parati, Eugenio/G-8765-2011; Gelati, Maurizio/H-2110-2016 OI Gelati, Maurizio/0000-0002-4828-9849 FU Fondazione IRCCS Istituto Neurologico "Carlo Besta" [LR8]; Italian Ministry of Health [RF2008.22]; National Heart, Lung, and Blood Institute [HL52585]; Department of Veterans Affairs Medical Research Service FX The authors thank Dr. Andrea Smith for the English review of the article. We thank Deborah Jones for her excellent technical assistance with the electron microscopy studies. This work was supported by Fondazione IRCCS Istituto Neurologico "Carlo Besta" (LR8); the Italian Ministry of Health (RF2008.22); National Heart, Lung, and Blood Institute (HL52585); and Merit Review Grant, Department of Veterans Affairs Medical Research Service. NR 65 TC 1 Z9 1 U1 0 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3384 EI 1937-3392 J9 TISSUE ENG PART C-ME JI Tissue Eng. Part C-Methods PD NOV PY 2011 VL 17 IS 11 BP 1109 EP 1120 DI 10.1089/ten.tec.2010.0622 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 844BB UT WOS:000296721200008 PM 21721991 ER PT J AU Ix, JH Chonchol, M Laughlin, GA Shlipak, MG Whooley, MA AF Ix, Joachim H. Chonchol, Michel Laughlin, Gail A. Shlipak, Michael G. Whooley, Mary A. TI Relation of Sex and Estrogen Therapy to Serum Fibroblast Growth Factor 23, Serum Phosphorus, and Urine Phosphorus: The Heart and Soul Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Menopause; fibroblast growth factor 23; phosphorus; estradiol; sex hormones ID CORONARY-ARTERY-DISEASE; NUTRITION EXAMINATION SURVEY; CHRONIC KIDNEY-DISEASE; VITAMIN-D METABOLITES; 3RD NATIONAL-HEALTH; POSTMENOPAUSAL WOMEN; MINERAL METABOLISM; OSTEOPOROTIC FRACTURES; PHOSPHATE REABSORPTION; CARDIOVASCULAR-DISEASE AB Background: Menopause is associated with urine phosphorus retention, which is mitigated by estrogen therapy. Fibroblast growth factor 23 (FGF-23) is a hormone originating from bone that regulates urine phosphorus excretion. Whether sex or estrogen therapy is associated with different FGF-23 levels is unknown. Study Design & Setting: Cross-sectional study of ambulatory individuals with prevalent cardiovascular disease. Predictors: Sex and, in women, use or nonuse of estrogen. Outcomes: Serum phosphorus, tubular maximum reabsorption of phosphorus indexed to glomerular filtration rate (TMP/GFR), and plasma FGF-23 concentrations. Results: For 987 participants, mean age was 67 +/- 11 years, 182 (18%) were women, and 46 (25%) were using estrogen. Mean estimated GFR was 71 +/- 23 (SD) mL/min/1.73 m(2). Compared with women who were not using estrogen, both women on estrogen therapy and men had significantly lower serum phosphorus concentrations, lower TMP/GFR values (indicating higher urine phosphorus excretion), and lower FGF-23 concentrations with adjustment for age, demographics, and kidney function (P < 0.001 for each). Mean FGF-23 levels were 68.7 (95% CI, 59.7-79.0) relative units (RU)/mL in non-estrogen-using women, 43.8 (95% CI, 41.2-46.5) RU/mL in men, and 45.1 (95% CI, 35.2-57.4) RU/mL in women using estrogen in adjusted analysis (P < 0.001). Limitations: Most participants were men. Estrogen therapy was not randomly assigned. Conclusions: Older women who are not using estrogen have higher FGF-23 levels than either men or women using estrogen. In the context of prior literature, these data suggest that postmenopausal phosphorus retention may stimulate higher FGF-23 concentrations after menopause. Am J Kidney Dis. 58(5): 737-745. 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 [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, San Diego, CA 92161 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, San Diego, CA 92161 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Chonchol, Michel] Univ Colorado Denver, Dept Med, Div Renal Dis & Hypertens, Aurora, CO USA. [Laughlin, Gail A.] Univ Calif San Diego, Dept Family & Prevent Med, Div Epidemiol, San Diego, CA 92103 USA. [Shlipak, Michael G.; Whooley, Mary A.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. [Shlipak, Michael G.; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Shlipak, Michael G.; Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Ix, JH (reprint author), Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA. EM joeix@ucsd.edu FU National Heart, Lung and Blood Institute [NHLBI: R01 HL096851, R01 HL079235]; American Heart Association (AHA) [0575021N]; Sandra Daugherty Foundation; Department of Veterans; Department of Veterans Affairs Health Services Research and Development service; American Federation for Aging Research; Robert Wood Johnson Foundation; Ischemia Research and Education Foundation FX This study was supported by grants from the National Heart, Lung and Blood Institute (NHLBI: R01 HL096851), American Heart Association (AHA 0575021N), and the Sandra Daugherty Foundation to Dr Ix. The Heart and Soul Study was supported by the Department of Veterans Epidemiology Merit Review Program, the Department of Veterans Affairs Health Services Research and Development service, the NHLBI (R01 HL079235), the American Federation for Aging Research (Paul Beeson Scholars Program), the Robert Wood Johnson Foundation (Generalist Physician Faculty Scholars Program), and the Ischemia Research and Education Foundation. NR 51 TC 27 Z9 27 U1 0 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 NOV PY 2011 VL 58 IS 5 BP 737 EP 745 DI 10.1053/j.ajkd.2011.06.011 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 839RF UT WOS:000296385700011 PM 21855188 ER PT J AU Diaz, MFP Pichler, RH Nicosia, RF Alpers, CE Smith, KD AF Diaz, Miguel F. Palma Pichler, Raimund H. Nicosia, Roberto F. Alpers, Charles E. Smith, Kelly D. TI Collapsing Glomerulopathy Associated With Natural Killer Cell Leukemia: A Case Report and Review of the Literature SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Focal segmental glomerulosclerosis; collapsing glomerulopathy; natural killer (NK) cell leukemia ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; NEPHROTIC SYNDROME; AFRICAN-AMERICANS; HEMOPHAGOCYTIC SYNDROME; PATHOGENESIS; NEPHROPATHY; APOL1; PODOCYTE; DISEASE; MYH9 AB We report a case of collapsing glomerulopathy associated with natural killer cell leukemia in a previously healthy 27-year-old African American man. An initial kidney biopsy showed findings concordant with the cellular variant of focal segmental glomerulosclerosis. A repeated biopsy 3 months later showed collapsing glomerulopathy, likely representing a morphologic evolution from a cellular variant into the collapsing glomerulopathy variant of focal segmental glomerulosclerosis. Collapsing glomerulopathy has been described in connection with a number of disparate disorders in which podocyte injury seems to be the common denominator. The close temporal association between clinical presentation and the development of nephropathy provides support for a direct pathogenic link between the underlying lymphoproliferative disorder and the glomerular lesions. We hypothesize that dysregulated cytokine production by the neoplastic cells led to podocyte alterations and eventually to the development of collapsing glomerulopathy. Am J Kidney Dis. 58(5):855-859. (C) 2011 by the National Kidney Foundation, Inc. C1 [Diaz, Miguel F. Palma; Nicosia, Roberto F.; Alpers, Charles E.; Smith, Kelly D.] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. [Pichler, Raimund H.] Univ Washington, Med Ctr, Div Nephrol, Seattle, WA 98195 USA. [Nicosia, Roberto F.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Diaz, MFP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, 10833 Le Conte Ave,CHS 13-145, Los Angeles, CA 90095 USA. EM fpalmadiaz@mednet.ucla.edu NR 25 TC 3 Z9 3 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 2011 VL 58 IS 5 BP 855 EP 859 DI 10.1053/j.ajkd.2011.07.011 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 839RF UT WOS:000296385700025 ER PT J AU Tulsky, JA Arnold, RM Alexander, SC Olsen, MK Jeffreys, AS Rodriguez, KL Skinner, CS Farrell, D Abernethy, AP Pollak, KI AF Tulsky, James A. Arnold, Robert M. Alexander, Stewart C. Olsen, Maren K. Jeffreys, Amy S. Rodriguez, Keri L. Skinner, Celette Sugg Farrell, David Abernethy, Amy P. Pollak, Kathryn I. TI Enhancing Communication Between Oncologists and Patients With a Computer-Based Training Program A Randomized Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ADVANCED CANCER; PRIMARY-CARE; SCOPE TRIAL; SKILLS; QUALITY; PHYSICIAN; EFFICACY; MODEL; TRUST; LIFE AB Background: Quality cancer care requires addressing patients' emotions, which oncologists infrequently do. Multiday courses can teach oncologists skills to handle emotion; however, such workshops are long and costly. Objective: To test whether a brief, computerized intervention improves oncologist responses to patient expressions of negative emotion. Design: Randomized, controlled, parallel-group trial stratified by site, sex, and oncologic specialty. Oncologists were randomly assigned to receive a communication lecture or the lecture plus a tailored CD-ROM. (ClinicalTrials. gov registration number: NCT00276627) Setting: Oncology clinics at a comprehensive cancer center and Veterans Affairs Medical Center in Durham, North Carolina, and a comprehensive cancer center in Pittsburgh, Pennsylvania. Participants: 48 medical, gynecologic, and radiation oncologists and 264 patients with advanced cancer. Intervention: Oncologists were randomly assigned in a 1: 1 ratio to receive an interactive CD-ROM about responding to patients' negative emotions. The CD-ROM included tailored feedback on the oncologists' own recorded conversations. Measurements: Postintervention audio recordings were used to identify the number of empathic statements and responses to patients' expressions of negative emotion. Surveys evaluated patients' trust in their oncologists and perceptions of their oncologists' communication skills. Results: Oncologists in the intervention group used more empathic statements (relative risk, 1.9 [95% Cl, 1.1 to 3.3]; P = 0.024) and were more likely to respond to negative emotions empathically (odds ratio, 2.1 [Cl, 1.1 to 4.2]; P = 0.028) than control oncologists. Patients of intervention oncologists reported greater trust in their oncologists than did patients of control oncologists (estimated mean difference, 0.1 [Cl, 0.0 to 0.2]; P = 0.036). There was no significant difference in perceptions of communication skills. Limitations: Long-term effects were not examined. The findings may not be generalizable outside of academic medical centers. Conclusion: A brief computerized intervention improves how oncologists respond to patients' expressions of negative emotions. Primary Funding Source: National Cancer Institute. C1 Duke Univ, Vet Affairs Med Ctr, Durham, NC 27705 USA. People Designs, Durham, NC USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Tulsky, JA (reprint author), Duke Univ, Ctr Palliat Care, Hock Plaza,Suite 1105,2424 Erwin Rd,Box 2720, Durham, NC 27705 USA. EM jtulsky@duke.edu FU National Cancer Institute [R01 CA100387] FX By grant R01 CA100387 from the National Cancer Institute. NR 38 TC 71 Z9 71 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 NOV 1 PY 2011 VL 155 IS 9 BP 593 EP U64 DI 10.7326/0003-4819-155-9-201111010-00007 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 842PW UT WOS:000296612400004 PM 22041948 ER PT J AU Qaseem, A Chou, R Humphrey, LL Starkey, M Shekelle, P AF Qaseem, Amir Chou, Roger Humphrey, Linda L. Starkey, Melissa Shekelle, Paul CA Amer Coll Phys TI Venous Thromboembolism Prophylaxis in Hospitalized Patients: A Clinical Practice Guideline From the American College of Physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID DEEP-VEIN THROMBOSIS; MOLECULAR-WEIGHT HEPARIN; ACUTE ISCHEMIC-STROKE; LOW-DOSE HEPARIN; PLACEBO-CONTROLLED TRIAL; ILL MEDICAL PATIENTS; FATAL PULMONARY-EMBOLISM; DOUBLE-BLIND; UNFRACTIONATED HEPARIN; RANDOMIZED-TRIAL AB Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on prophylaxis of venous thromboembolism for hospitalized nonsurgical patients (medical patients and patients with acute stroke). Methods: This guideline is based on published literature on the topic from 1950 through April 2011 that was identified by using MEDLINE, the Cochrane Library, and reference lists of pertinent randomized trials and systematic reviews to identify additional reports. Searches were limited to randomized trials and English-language publications. The primary outcome for this guideline was total mortality up to 120 days after randomization. Secondary outcomes included symptomatic deep venous thrombosis; all pulmonary embolisms; fatal pulmonary embolism; all bleeding events; major bleeding events; and, for mechanical prophylaxis, effects on skin. This guideline grades the evidence and recommendations by using the ACP's clinical practice guidelines grading system. Recommendation 1: ACP recommends assessment of the risk for thromboembolism and bleeding in medical (including stroke) patients prior to initiation of prophylaxis of venous thromboembolism (Grade: strong recommendation, moderate-quality evidence). Recommendation 2: ACP recommends pharmacologic prophylaxis with heparin or a related drug for venous thromboembolism in medical (including stroke) patients unless the assessed risk for bleeding outweighs the likely benefits (Grade: strong recommendation, moderate-quality evidence). Recommendation 3: ACP recommends against the use of mechanical prophylaxis with graduated compression stockings for prevention of venous thromboembolism (Grade: strong recommendation, moderate-quality evidence). Policy Implication: ACP does not support the application of performance measures in medical (including stroke) patients that promotes universal venous thromboembolism prophylaxis regardless of risk. C1 [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA 19106 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Qaseem, A (reprint author), Amer Coll Physicians, 190 N Independence Mall W, Philadelphia, PA 19106 USA. EM aqaseem@acponline.org FU ACP FX Financial support for the development of this guideline comes exclusively from the ACP operating budget. NR 50 TC 93 Z9 97 U1 1 U2 8 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 NOV 1 PY 2011 VL 155 IS 9 BP 625 EP U118 DI 10.7326/0003-4819-155-9-201111010-00011 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 842PW UT WOS:000296612400007 PM 22041951 ER PT J AU Koontz, AM Kankipati, P Lin, YS Cooper, RA Boninger, ML AF Koontz, Alicia M. Kankipati, Padmaja Lin, Yen-Sheng Cooper, Rory A. Boninger, Michael L. TI Upper limb kinetic analysis of three sitting pivot wheelchair transfer techniques SO CLINICAL BIOMECHANICS LA English DT Article DE Biomechanics; Upper limb pain; Spinal cord injury; Activities of daily living; Wheelchair ID SPINAL-CORD-INJURY; UPPER EXTREMITY; BIOMECHANICAL ANALYSIS; INDIVIDUALS; SHOULDER; USERS; PARAPLEGIA; SYSTEM; KINEMATICS; MANEUVER AB Background: The objective of this study was to investigate differences in shoulder, elbow and hand kinetics while performing three different SPTs that varied in terms of hand and trunk positioning. Methods: Fourteen unimpaired individuals (8 male and 6 female) performed three variations of sitting pivot transfers in a random order from a wheelchair to a level tub bench. Two transfers involved a forward flexed trunk (head-hips technique) and the third with the trunk remaining upright. The two transfers involving a head hips technique were performed with two different leading hand initial positions. Motion analysis equipment recorded upper body movements and force sensors recorded hand reaction forces. Shoulder and elbow joint and hand kinetics were computed for the lift phase of the transfer. Findings: Transferring using either of the head hips techniques compared to the trunk upright style of transferring resulted in reduced superior forces at the shoulder (P<0.002), elbow (P<0.004) and hand (P<0.013). There was a significant increase in the medial forces in the leading elbow (P=0.049) for both head hip transfers and the trailing hand for the head hip technique with the arm further away from the body (P<0.028). The head hip techniques resulted in higher shoulder external rotation, flexion and extension moments compared to the trunk upright technique (P<0.021). Interpretation: Varying the hand placement and trunk positioning during transfers changes the load distribution across all upper limb joints. The results of this study may be useful for determining a technique that helps preserve upper limb function overtime. Published by Elsevier Ltd. C1 [Koontz, Alicia M.; Kankipati, Padmaja; Lin, Yen-Sheng; Cooper, Rory A.; Boninger, Michael L.] Dept Vet Affairs, Human Engn Res Labs, Pittsburgh, PA USA. [Koontz, Alicia M.; Kankipati, Padmaja; Lin, Yen-Sheng; Cooper, Rory A.; Boninger, Michael L.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Cooper, Rory A.; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Koontz, AM (reprint author), VA Pittsburgh Hlth Care Syst, Human Engn Res Labs 151R1 H, 7180 Highland Dr,151R1-H, Pittsburgh, PA 15206 USA. EM akoontz@pitt.edu OI Boninger, Michael/0000-0001-6966-919X FU VA Rehabilitation Research RD Services; National Institute on Disability and Rehabilitation Research; National Institute of Health, Center for Injury Research Control [VA-RRD E3589V, B3079R NIDRR H133A011107, NIH R49/CCR310285-06] FX Funding for this study was provided by the VA Rehabilitation Research R&D Services and the National Institute on Disability and Rehabilitation Research and the National Institute of Health, Center for Injury Research Control (VA-RR&D E3589V and B3079R NIDRR H133A011107, NIH R49/CCR310285-06). The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government. NR 27 TC 14 Z9 14 U1 2 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD NOV PY 2011 VL 26 IS 9 BP 923 EP 929 DI 10.1016/j.clinbiomech.2011.05.005 PG 7 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 840AK UT WOS:000296410400006 PM 21664733 ER PT J AU Merchant, RM Yang, L Becker, LB Berg, RA Nadkarni, V Nichol, G Carr, BG Mitra, N Bradley, SM Abella, BS Groeneveld, PW AF Merchant, Raina M. Yang, Lin Becker, Lance B. Berg, Robert A. Nadkarni, Vinay Nichol, Graham Carr, Brendan G. Mitra, Nandita Bradley, Steven M. Abella, Benjamin S. Groeneveld, Peter W. CA American Heart Assoc Get Guideline TI Incidence of treated cardiac arrest in hospitalized patients in the United States SO CRITICAL CARE MEDICINE LA English DT Article DE cardiopulmonary resuscitation; heart arrest; resuscitation ID AMERICAN-HEART-ASSOCIATION; EMERGENCY CARDIOVASCULAR CARE; CARDIOPULMONARY-RESUSCITATION; NATIONAL REGISTRY; SURVIVAL; GUIDELINES; IMPLEMENTATION; DISPARITIES; COUNCIL; ORDERS AB Objective: The incidence and incidence over time of cardiac arrest in hospitalized patients is unknown. We sought to estimate the event rate and temporal trends of adult inhospital cardiac arrest treated with a resuscitation response. Design: Three approaches were used to estimate the inhospital cardiac arrest event rate. First approach: calculate the inhospital cardiac arrest event rate at hospitals (n = 433) in the Get With The Guidelines-Resuscitation registry, years 2003-2007, and multiply this by U. S. annual bed days. Second approach: use the Get With The Guidelines-Resuscitation inhospital cardiac arrest event rate to develop a regression model (including hospital demographic, geographic, and organizational factors), and use the model coefficients to calculate predicted event rates for acute care hospitals (n = 5445) responding to the American Hospital Association survey. Third approach: classify acute care hospitals into groups based on academic, urban, and bed size characteristics, and determine the average event rate for Get With The Guidelines-Resuscitation hospitals in each group, and use weighted averages to calculate the national inhospital cardiac arrest rate. Annual event rates were calculated to estimate temporal trends. Setting: Get With The Guidelines-Resuscitation registry. Patients: Adult inhospital cardiac arrest with a resuscitation response. Measurements and Main Results: The mean adult treated inhospital cardiac arrest event rate at Get With The Guidelines-Resuscitation hospitals was 0.92/1000 bed days (interquartile range 0.58 to 1.2/1000). In hospitals (n = 150) contributing data for all years of the study period, the event rate increased from 2003 to 2007. With 2.09 million annual U. S. bed days, we estimated 192,000 inhospital cardiac arrests throughout the United States annually. Based on the regression model, extrapolating Get With The Guidelines-Resuscitation hospitals to hospitals participating in the American Hospital Association survey projected 211,000 annual inhospital cardiac arrests. Using weighted averages projected 209,000 annual U. S. inhospital cardiac arrests. Conclusions: There are approximately 200,000 treated cardiac arrests among U. S. hospitalized patients annually, and this rate may be increasing. This is important for understanding the burden of inhospital cardiac arrest and developing strategies to improve care for hospitalized patients. (Crit Care Med 2011; 39: 2401-2406) C1 [Merchant, Raina M.; Becker, Lance B.; Carr, Brendan G.; Abella, Benjamin S.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Berg, Robert A.; Nadkarni, Vinay] Univ Penn, Dept Anesthesiol & Crit Care Med, Philadelphia, PA 19104 USA. [Mitra, Nandita] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Yang, Lin; Groeneveld, Peter W.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Berg, Robert A.; Nadkarni, Vinay] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Nichol, Graham; Bradley, Steven M.] Univ Washington, Seattle, WA 98195 USA. [Groeneveld, Peter W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Merchant, RM (reprint author), Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. EM raina.merchant@uphs.upenn.edu OI Abella, Benjamin/0000-0003-2521-0891 FU Robert Wood Johnson Foundation at University of Pennsylvania; Institute for Health Technology Studies (Washington, DC); National Heart, Lung, and Blood Institute [1-R01-HL086919]; Pennsylvania Department of Health; Department of Veterans Affairs' Health Services Research and Development Service [RRP 09-117]; Philips Healthcare, Seattle, WA; Laerdal Medical, Stavanger, Norway; NIH, Bethesda, MD; Cardiac Science, Bothell, Washington; Laerdal Foundation for Acute Care Medicine, Stavanger, Norway; NIH; Asmund S. Laerdal Foundation for Acute Medicine; NHLBI; Medtronic Foundation; AHRQ; Medivance Corporation, Louisville, CO; Philips Healthcare, Andover, MA; Doris Duke Foundation, New York City, NY; American Heart Association, Dallas, TX FX Supported, in part, by funding from the Robert Wood Johnson Foundation Clinical Scholars program at the University of Pennsylvania (Merchant); an unrestricted grant from the Institute for Health Technology Studies (Washington, DC); grant 1-R01-HL086919 from the National Heart, Lung, and Blood Institute; and a grant from the Pennsylvania Department of Health, which specifically disclaims responsibility for any analyses, interpretations, or conclusions. Dr. Groeneveld was additionally supported by a Research Career Development Award (RRP 09-117) from the Department of Veterans Affairs' Health Services Research and Development Service.; Dr. Becker received speaker honoraria/consultant fees from Philips Healthcare, Seattle, WA; institutional grant/research support from Philips Healthcare, Seattle, WA, Laerdal Medical, Stavanger, Norway, NIH, Bethesda, MD, and Cardiac Science, Bothell, Washington. Dr. Nadkarni received institutional grant/research support from the Laerdal Foundation for Acute Care Medicine, Stavanger, Norway, and NIH, Bethesda, MD. Dr. Nichol received institutional grant/research support from NIH, the Asmund S. Laerdal Foundation for Acute Medicine, the NHLBI, the Medtronic Foundation, and has research collaborations with Gambro Renal, Lakewood, CO, Sotera Wireless, San Diego, CA, Lifebridge Medizintechnik AG, Ampfing, Germany. Dr. Carr received institutional grant/research support from NIH, and AHRQ. Dr. Abella received speaker honoraria/consultant fees from Philips Healthcare, Seattle, WA, Medivance Corporation, Louisville, CO; and institutional grant/research support: Philips Healthcare, Andover, MA, Doris Duke Foundation, New York City, NY, American Heart Association, Dallas, TX, NIH, Bethesda, MD. The remaining authors have not disclosed any potential conflict of interests. NR 36 TC 128 Z9 129 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2011 VL 39 IS 11 BP 2401 EP 2406 DI 10.1097/CCM.0b013e3182257459 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 841JV UT WOS:000296509500002 PM 21705896 ER PT J AU Byrd, JB Ho, PM AF Byrd, James Brian Ho, P. Michael TI The possibility of unmeasured confounding variables in observational studies: a forgotten fact? SO HEART LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; CLOPIDOGREL; OUTCOMES; DISEASE C1 [Byrd, James Brian] Univ Colorado, Div Cardiol, Denver, CO 80202 USA. [Ho, P. Michael] Denver VA Med Ctr, Cardiol Sect, Denver, CO USA. RP Ho, PM (reprint author), 1055 Clermont St, Denver, CO 80220 USA. EM michael.ho@coloradooutcomes.org OI Byrd, J. Brian/0000-0002-0509-3520 NR 10 TC 3 Z9 3 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD NOV PY 2011 VL 97 IS 22 BP 1815 EP 1816 DI 10.1136/heartjnl-2011-300630 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 837LF UT WOS:000296203800001 PM 21795300 ER PT J AU Sajatovic, M Al Jurdi, R Gildengers, A Greenberg, RL Tenhave, T Bruce, ML Mulsant, B Young, RC AF Sajatovic, Martha Al Jurdi, Rayan Gildengers, Ariel Greenberg, Rebecca L. Tenhave, Thomas Bruce, Martha L. Mulsant, Benoit Young, Robert C. TI Depression symptom ratings in geriatric patients with bipolar mania SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE bipolar disorder; geriatrics; older; depression; rating scales ID OLDER-ADULTS; MIXED MANIA; CLINICAL-TRIALS; II DISORDERS; SCALE; SENSITIVITY; DIAGNOSIS; SAMPLE; PURE AB Objective: Given the paucity of information available regarding standardized ratings of depression symptoms in bipolar manic states, and in particular those in older adults, we explored depression ratings in symptomatic participants in a multicenter study of treatment of bipolar I disorder in late life. Methods: Baseline data was obtained from the first 100 patients enrolled in an NIMH-funded, 9-week, randomized, double-blind RCT comparing treatment with lithium or valproate in patients of age 60 years and older with Type I Bipolar mania or hypomania. This multi-site study was conducted at six academic medical centers in the United States and enrolled inpatients and outpatients with a total Young Mania Rating Scale (YMRS) score of 18 or greater. Depressive symptoms were evaluated with the Hamilton Depression Rating Scale (HAM-D) and the Montgomery-Asberg Depression Rating Scale (MADRS). The criterion for at least moderate bipolar depressive symptoms was the European College of Neuropsychopharmacology (ECNP) Consensus Meeting definition of HAM-D 17 total score >20. Results: Eleven percent of patients had mixed symptoms defined by depression scale severity according to ECNP criterion. In the overall sample, total scores on the two depression scales were highly correlated. Total YMRS scores of this mixed symptom group were similar to the remainder of the sample. Conclusions: These preliminary findings suggest that moderate to severe depressive symptoms occur in about one in ten bipolar manic elders. Future studies are needed to further evaluate symptom profiles, clinical correlates, and treatments for bipolar older adults with combined manic and depressive symptoms. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Sajatovic, Martha] Case Western Reserve Univ, Sch Med, Dept Psychiat, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Al Jurdi, Rayan] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Psychiat, Menninger Dept Psychiat, Houston, TX 77030 USA. [Gildengers, Ariel] Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Greenberg, Rebecca L.; Bruce, Martha L.; Young, Robert C.] Weill Cornell Med Coll, Dept Psychiat, White Plains, NY USA. [Tenhave, Thomas] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Mulsant, Benoit] Univ Toronto, Geriatr Mental Hlth Program, Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Mulsant, Benoit] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. RP Sajatovic, M (reprint author), Case Western Reserve Univ, Sch Med, Dept Psychiat, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. EM martha.sajatovic@uhhospitals.org RI Sajatovic, Martha/I-8001-2014 OI Young, Robert/0000-0002-6380-6314 FU National Institute of Mental Health (NIMH) [U01 MH074091-01]; National Center for Research Resources (NCRR), National Institutes of Health (NIH) [M01 RR00080, UL1 RR024989] FX This study was supported by National Institute of Mental Health (NIMH) grant U01 MH074091-01 (all authors); 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.; The project described was supported by Grant Number M01 RR00080 and UL1 RR024989 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. NR 36 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD NOV PY 2011 VL 26 IS 11 BP 1201 EP 1208 DI 10.1002/gps.2664 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 840NK UT WOS:000296447300013 PM 21360754 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Birth cohort patterns of gastric cancer and peptic ulcer among non-whites in the USA SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID TIME TRENDS; HELICOBACTER-PYLORI; MORTALITY; SALT; INFECTION; GERMANY; DISEASE; RATES; RISK AB Background The aim of this study was to follow the long-term trends of mortality from gastric cancer, gastric ulcer and duodenal ulcer in the USA. It was hypothesised that the time trends among different ethnic groups would be shaped by similar birth cohort patterns. Methods The US ulcer and cancer data were available from 1923 to 2006 and 1930 to 2006, respectively. Age-specific death rates were calculated for consecutive 10-year periods and 10-year age groups, stratified by sex and race. They were plotted against the period of death as period-age contours and against the period of birth as cohort-age contours. The time trends were also summarised as standardised cohort mortality ratios. Results The occurrence of birth cohort patterns with an initial rise and a subsequent decline was observed in gastric cancer and both ulcer types. It occurred similarly in white and non-white population, as well as men and women. In all ethnic groups alike, the initial rise in mortality from gastric cancer and gastric ulcer preceded the rise of duodenal ulcer by 10-20 years. The two time lags between gastric cancer and gastric ulcer and between gastric and duodenal ulcer were most pronounced in white patients. In non-white patients, the rise of gastric cancer occurred later than in white patients and coincided with that of gastric ulcer. The initial rise in mortality from gastric cancer was more evident in non-white than in white patients. Conclusion The birth cohort pattern has shaped the time trends of Helicobacter pylori-related disease similarly among different ethnic and socioeconomic groups. Its cause remains unknown and warrants further investigation. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Gastroenterol Sect, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Gastroenterol Sect, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 31 TC 0 Z9 0 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD NOV PY 2011 VL 65 IS 11 BP 1059 EP 1064 DI 10.1136/jech.2010.121368 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 836VK UT WOS:000296143300017 PM 21597103 ER PT J AU Dixon, JA Goodman, AM Gaillard, WF Rivers, WT McKinney, RA Mukherjee, R Baker, NL Ikonomidis, JS Spinale, FG AF Dixon, Jennifer A. Goodman, Amy M. Gaillard, William F., II Rivers, William T. McKinney, Richard A. Mukherjee, Rupak Baker, Nathaniel L. Ikonomidis, John S. Spinale, Francis G. TI Hemodynamics and myocardial blood flow patterns after placement of a cardiac passive restraint device in a model of dilated cardiomyopathy SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID INDUCED HEART-FAILURE; TACHYCARDIA-INDUCED CARDIOMYOPATHY; FUNCTIONAL MITRAL REGURGITATION; CONVERTING ENZYME-INHIBITION; ACORN CLINICAL-TRIAL; SUPPORT DEVICE; COMBINATION THERAPY; INFARCTION; REDUCTION; ADENOSINE AB Background: The present study examined a cardiac passive restraint device which applies epicardial pressure (HeartNet Implant; Paracor Medical, Inc, Sunnyvale, Calif) in a clinically relevant model of dilated cardiomyopathy to determine effects on hemodynamic and myocardial blood flow patterns. Methods: Dilated cardiomyopatht was established in 10 pigs (3 weeks of atrial pacing, 240 beats/min). Hemodynamic parameters and regional left ventricular blood flow were measured under baseline conditions and after acute placement of the HeartNet Implant. Measurements were repeated after adenosine infusion, allowing maximal coronary vasodilation and coronary flow reserve to be determined. Results: Left ventricular dilation and systolic dysfunction occurred relative to baseline as measured by echocardiography. Left ventricular end-diastolic dimension increased and left ventricular fractional shortening decreased (3.8 +/- 0.1 vs 6.1 +/- 0.2 cm and 31.6% +/- 0.5% vs 16.2% +/- 2.1%, both P < .05, respectively), consistent with the dilated cardiomyopathy phenotype. The HeartNet Implant was successfully deployed without arrhythmias and a computed median mid-left ventricular epicardial pressure of 1.4 mm Hg was applied by the HeartNet Implant throughout the cardiac cycle. Acute HeartNet placement did not adversely affect steady state hemodynamics. With the HeartNet Implant in place, coronary reserve was significantly blunted. Conclusions: In a large animal model of dilated cardiomyopathy, the cardiac passive restraint device did not appear to adversely affect basal resting myocardial blood flow. However, after acute HeartNet Implant placement, left ventricular maximal coronary reserve was blunted. These unique results suggest that cardiac passive restraint devices that apply epicardial transmural pressure can alter myocardial blood flow patterns in a model of dilated cardiomyopathy. Whether this blunting of coronary reserve holds clinical relevance with chronic passive restraint device placement remains unestablished. (J Thorac Cardiovasc Surg 2011;142:1038-45) C1 [Dixon, Jennifer A.; Gaillard, William F., II; Rivers, William T.; McKinney, Richard A.; Mukherjee, Rupak; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. [Dixon, Jennifer A.; Gaillard, William F., II; Rivers, William T.; McKinney, Richard A.; Mukherjee, Rupak; Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Goodman, Amy M.; Ikonomidis, John S.] Paracor Med Inc, Sunnyvale, CA USA. [Baker, Nathaniel L.] Med Univ S Carolina, Dept Biostat & Epidemiol, Charleston, SC 29425 USA. RP Spinale, FG (reprint author), Strom Thurmond Res Ctr, 114 Doughty St,Suite 625, Charleston, SC 29425 USA. EM wilburnm@musc.edu FU Paracor Medical, Inc; National Institutes of Health [HL81692, HL87134]; Veterans' Affairs Health Administration FX This research was supported by a grant from Paracor Medical, Inc, as well as by National Institutes of Health grants HL81692 and HL87134 and a Merit Award from the Veterans' Affairs Health Administration. NR 26 TC 8 Z9 8 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD NOV PY 2011 VL 142 IS 5 BP 1038 EP 1045 DI 10.1016/j.jtcvs.2010.09.065 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 839AT UT WOS:000296337500015 PM 21397269 ER PT J AU Shen, Q Duong, TQ AF Shen, Qiang Duong, Timothy Q. TI Background suppression in arterial spin labeling MRI with a separate neck labeling coil SO NMR IN BIOMEDICINE LA English DT Article DE arterial spin labeling; rodents; cerebral blood flow; cerebral perfusion; high fields; inversion recovery ID CEREBRAL-BLOOD-FLOW; TRANSIT-TIME; RAT-BRAIN; TISSUE WATER; PERFUSION; DIFFUSION; INVERSION; ISCHEMIA; EXCHANGE; SIGNAL AB In arterial spin labeling (ASL) MRI to measure cerebral blood flow (CBF), pair-wise subtraction of temporally adjacent non-labeled and labeled images often can not completely cancel the background static tissue signal because of temporally fluctuating physiological noise. While background suppression (BS) by inversion nulling improves CBF temporal stability, imperfect pulses compromise CBF contrast. Conventional BS techniques may not be applicable in small animals because the arterial transit time is short. This study presents a novel approach of BS to overcome these drawbacks using a separate 'neck' radiofrequency coil for ASL and a 'brain' radiofrequency coil for BS with the inversion pulse placed before spin labeling. The use of a separate 'neck' coil for ASL should also improve ASL contrast. This approach is referred to as the inversion-recovery BS with the two-coil continuous ASL (IR-cASL) technique. The temporal and spatial contrast-to-noise characteristics of basal CBF and CBF-based fMRI of hypercapnia and forepaw stimulation in rats at 7 Tesla were analyzed. IR-cASL yielded two times better temporal stability and 2.0-2.3 times higher functional contrast-to-noise ratios for hypercapnia and forepaw stimulation compared with cASL without BS in the same animals. The Bloch equations were modified to provide accurate CBF quantification at different levels of BS and for multislice acquisition where different slices have different degree of BS and residual degree of labeling. Improved basal CBF and CBF-based fMRI sensitivity should lead to more accurate CBF quantification and should prove useful for imaging low CBF conditions such as in white matter and stroke. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Shen, Qiang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Shen, Qiang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Shen, Qiang; 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.] Dept Vet Affairs, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), UTHSCSA, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Shen, Qiang/B-8784-2008; Duong, Timothy/B-8525-2008 OI Shen, Qiang/0000-0002-4287-3403; FU NIH [R01-NS45879, R01EY014211, R01EY018855]; American Heart Association [SDG-0430020N, SDG-0830293N]; VA MERIT award FX This work was supported in part by the NIH (R01-NS45879, R01EY014211 and R01EY018855), the American Heart Association (SDG-0430020N and SDG-0830293N) and a VA MERIT award. NR 33 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD NOV PY 2011 VL 24 IS 9 BP 1111 EP 1118 DI 10.1002/nbm.1666 PG 8 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 840DT UT WOS:000296419200011 PM 21294207 ER PT J AU Sher, L AF Sher, L. TI Teaching medical professionals about suicide prevention: what's missing? SO QJM-AN INTERNATIONAL JOURNAL OF MEDICINE LA English DT Article ID PSYCHIATRY RESIDENCY PROGRAMS; INPATIENT SUICIDE; CLINICAL-PSYCHOLOGY; NATIONAL-SURVEY; DEPRESSION; PATIENT; RISK; HOSPITALIZATION; INTERVENTION; ASSESSMENTS C1 [Sher, L.] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. [Sher, L.] Mt Sinai Sch Med, 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 leo.sher@mssm.edu NR 43 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1460-2725 EI 1460-2393 J9 QJM-INT J MED JI QJM-An Int. J. Med. PD NOV PY 2011 VL 104 IS 11 BP 1005 EP 1008 DI 10.1093/qjmed/hcr125 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 839GX UT WOS:000296354600018 PM 21824917 ER PT J AU Baker, JF George, M Baker, DG Toedter, G Von Feldt, JM Leonard, MB AF Baker, Joshua F. George, Michael Baker, Daniel G. Toedter, Gary Von Feldt, Joan M. Leonard, Mary B. TI Associations between body mass, radiographic joint damage, adipokines and risk factors for bone loss in rheumatoid arthritis SO RHEUMATOLOGY LA English DT Article DE Rheumatoid arthritis; Body mass index; Erosion; Disease activity; Adipokines; Adiponectin ID SERUM CREATININE; PLASMA-LEVELS; ADIPONECTIN; INDEX; OSTEOPOROSIS; DESTRUCTION; ANTIBODY; OBESITY; LEPTIN; WOMEN AB Objective. To evaluate the association between BMI and radiographic joint damage (RJD) in RA. Methods. van der Heijde-Sharp (vdHS) erosion scores were determined in 499 participants with RA, ages 18-85 years, while enrolled in a clinical trial of golimumab (GO-BEFORE trial). Subjects were MTX and biologic therapy naive. Multivariable logistic regressions determined the odds of prevalent RJD (defined as vdHS score > 10) according to BMI category. Longitudinal analyses evaluated the association between BMI category and progression of vdHS score over 52 weeks. Analyses in a subset of 100 participants examined the association between adipokines and vdHS scores. Results. At enrolment and 52 weeks, 37.6 and 43.6% of participants had RJD. Compared with normal weight, obese subjects had lower odds of RJD [0.40 (95% CI 0.22, 0.74); P = 0.003], and underweight subjects had greater odds [3.86 (95% CI 1.66, 9.00); P = 0.002] at baseline, adjusted for demographic and disease characteristics. The baseline associations between BMI category and RJD were greater among participants with multiple risk factors for bone loss (female > 50 years, smoking, glucocorticoid exposure and vitamin D deficiency); test for interaction P = 0.05. Adjustment for adiponectin levels did not attenuate the association between BMI and vdHS scores. Baseline BMI and change in weight did not independently predict radiographic progression (P > 0.1). Conclusions. Higher BMI was independently associated with less RJD and was greatest in participants with risk factors for bone loss. Future studies are needed to examine the associations between RJD, obesity, weight loss and osteoporosis. C1 [Baker, Joshua F.; George, Michael] Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Baker, Daniel G.] Centocor Res & Dev, Clin Immunol, Malvern, PA USA. [Leonard, Mary B.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Toedter, Gary] Centocor Res & Dev, Biomarker, Malvern, PA USA. [Von Feldt, Joan M.] Vet Affairs Med Ctr, Div Rheumatol, Philadelphia, PA USA. [Leonard, Mary B.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. RP Baker, JF (reprint author), Hosp Univ Penn, Dept Med, Div Rheumatol, 8 Penn Tower Bldg,34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bakerjo@uphs.upenn.edu NR 29 TC 20 Z9 20 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD NOV PY 2011 VL 50 IS 11 BP 2100 EP 2107 DI 10.1093/rheumatology/ker294 PG 8 WC Rheumatology SC Rheumatology GA 838MH UT WOS:000296295800025 PM 21890621 ER PT J AU Becker, BW Thames, AD Woo, E Castellon, SA Hinkin, CH AF Becker, Brian W. Thames, April D. Woo, Ellen Castellon, Steven A. Hinkin, Charles H. TI Longitudinal Change in Cognitive Function and Medication Adherence in HIV-Infected Adults SO AIDS AND BEHAVIOR LA English DT Article DE HIV; Medication adherence; HAART; Cognitive decline; Memory ID ANTIRETROVIRAL THERAPY; NEUROPSYCHOLOGICAL PERFORMANCE; PROSPECTIVE MEMORY; DRUG-RESISTANCE; VIRAL LOAD; COHORT; HAART; INDIVIDUALS; IMPAIRMENT; PREDICTORS AB Neuropsychological (NP) dysfunction has been linked to poor medication adherence among HIV-infected adults. However, there is a dearth of research examining longitudinal changes in the relationship between NP status and adherence rates. We hypothesized that declines in NP functioning would be associated with a corresponding decline in medication adherence while stable NP functioning would be associated with stable or improving adherence rates. Participants included 215 HIV-infected adults who underwent cognitive testing at study entry and six months later. Compared to the NP stable group, the NP decline group showed a greater drop in adherence rates. Further analysis revealed that, beyond global NP, learning and memory was significantly associated with changes in adherence rates. These findings further support the link between cognitive functioning and medication adherence and illustrates the importance of documenting changes in cognitive abilities for identifying individuals at risk for poor adherence. C1 [Becker, Brian W.; Castellon, Steven A.; Hinkin, Charles H.] VA Greater Angeles Hlth Care Syst, Neuropsychol Lab 256, Los Angeles, CA 90073 USA. [Becker, Brian W.; Thames, April D.; Woo, Ellen; Castellon, Steven A.; Hinkin, Charles H.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Becker, BW (reprint author), VA Greater Angeles Hlth Care Syst, Neuropsychol Lab 256, 11301 Wilshire, Los Angeles, CA 90073 USA. EM brian.becker@va.gov RI Thames, April/K-1964-2014 OI Thames, April/0000-0001-8414-7189 FU NIDA NIH HHS [R01 DA013799, R01 DA13799]; NIMH NIH HHS [R25 MH080663, T32 MH019535, T32 MH19535] NR 27 TC 31 Z9 31 U1 0 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD NOV PY 2011 VL 15 IS 8 BP 1888 EP 1894 DI 10.1007/s10461-011-9924-z PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 831MN UT WOS:000295735200030 PM 21437726 ER PT J AU Toosi, KK Impink, BG Baker, NA Boninger, ML AF Toosi, Kevin K. Impink, Bradley G. Baker, Nancy A. Boninger, Michael L. TI Effects of Computer Keyboarding on Ultrasonographic Measures of the Median Nerve SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE carpal tunnel syndrome; computer keyboarding; median nerve; ultrasonography; ultrasound ID CARPAL-TUNNEL-SYNDROME; CUMULATIVE TRAUMA DISORDERS; MUSCULOSKELETAL DISORDERS; RISK-FACTORS; GENERAL-POPULATION; UPPER EXTREMITY; OFFICE WORKERS; SONOGRAPHY; DIAGNOSIS; WRIST AB Background Keyboarding is a highly repetitive daily task and has been linked to musculoskeletal disorders of the upper extremity. However, the effect of keyboarding on median nerve injuries is not well understood. The purpose of this study was to use ultrasonographic measurements to determine whether continuous keyboarding can cause acute changes in the median nerve. Methods Ultrasound images of the median nerve from 21 volunteers were captured at the levels of the pisiform and distal radius prior to and following a prolonged keyboarding task (i.e., 1 hr of continuous keyboarding). Images were analyzed by a blinded investigator to quantify the median nerve characteristics. Changes in the median nerve ultrasonographic measures as a result of continuous keyboarding task were evaluated. Results Cross-sectional areas at the pisiform level were significantly larger in both dominant (P = 0.004) and non-dominant (P = 0.001) hands following the keyboarding task. Swelling ratio was significantly greater in the dominant hand (P = 0.020) after 60 min of keyboarding when compared to the baseline measures. Flattening ratios were not significantly different in either hand as a result of keyboarding. Conclusion We were able to detect an acute increase in the area of the median nerve following 1 hr of keyboarding with a computer keyboard. This suggests that keyboarding has an impact on the median nerve. Further studies are required to understand this relationship, which would provide insight into the pathophysiology of median neuropathies such as carpal tunnel syndrome. Am. J. Ind. Med. 54:826-833, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Toosi, Kevin K.; Impink, Bradley G.; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, Pittsburgh, PA 15206 USA. [Toosi, Kevin K.; Impink, Bradley G.; Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Toosi, Kevin K.; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Baker, Nancy A.] Univ Pittsburgh, Dept Occupat Therapy, Pittsburgh, PA USA. RP Boninger, ML (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, 7180 Highland Dr 151R1-H,Bldg 4,2nd Floor,East Wi, Pittsburgh, PA 15206 USA. EM boninger@pitt.edu OI Boninger, Michael/0000-0001-6966-919X FU U.S. Department of Veterans Affairs [B3142C]; National Institutes of Health [T32HD049307] FX This material is the result of work supported with resources and the use of facilities at the Human Engineering Research Laboratories, VA Pittsburgh Healthcare System. This study was supported by the U.S. Department of Veterans Affairs (B3142C) and the National Institutes of Health (T32HD049307). The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government. NR 40 TC 12 Z9 12 U1 0 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2011 VL 54 IS 11 BP 826 EP 833 DI 10.1002/ajim.20983 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 837YF UT WOS:000296248400003 PM 21739468 ER PT J AU Schneider, BC Lichtenberg, PA AF Schneider, Brooke C. Lichtenberg, Peter A. TI Influence of Reading Ability on Neuropsychological Performance in African American Elders SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Assessment; Elderly; Geriatrics; Aging; Norms; Normative studies ID NORMATIVE DATA; OLDER-ADULTS; LEVEL; EDUCATION; ACCULTURATION; IMPAIRMENT; DEMENTIA; NORMS AB Use of normative data stratified by education may result in misclassification of African American older adults because reading ability, an estimate of educational attainment, is lower than reported years of education for some African American elders. This study examined the contribution of reading ability versus education to neuropsychological test performance in 86 community-dwelling African American elders ages 56-91 with 8-18 years of education. Hierarchical multiple regression analyses revealed that reading ability, but not education, was significantly associated with performances on the Trail Making Test, Controlled Oral Word Association Test, Animal Naming, Digit Span, and the Stroop test. Reading ability was not significantly related to performances on measures of memory. Medium to large effect sizes (Cohen's d = 0.58-1.41) were found when comparing mean performances on neuropsychological measures in groups with low versus high reading scores. Results indicate that reading ability contributes beyond educational attainment to performances on some neuropsychological measures among African American elders. These findings have implications for reducing misclassification among minority populations through the use of appropriate normative data. C1 [Schneider, Brooke C.] Greater Los Angeles VA Healthcare Ctr, Psychol Serv, W Los Angeles VA, Los Angeles, CA 90073 USA. [Lichtenberg, Peter A.] Wayne State Univ, Inst Gerontol, Detroit, MI 48202 USA. RP Schneider, BC (reprint author), Greater Los Angeles VA Healthcare Ctr, Psychol Serv, W Los Angeles VA, 11301 Wilshire Blvd,Room A206, Los Angeles, CA 90073 USA. EM brooke.schneider@va.gov FU NIH/NIA [T32 AG00275-06] FX This work was supported by the NIH/NIA Aging and Urban Health Pre-doctoral Research Training Grant (T32 AG00275-06). NR 30 TC 2 Z9 2 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD NOV PY 2011 VL 26 IS 7 BP 624 EP 631 DI 10.1093/arclin/acr062 PG 8 WC Psychology, Clinical; Psychology SC Psychology GA 836FF UT WOS:000296094800006 PM 21835850 ER PT J AU Grenon, SM Saary, J AF Grenon, S. Marlene Saary, Joan TI Challenges in Aerospace Medicine Education SO AVIATION SPACE AND ENVIRONMENTAL MEDICINE LA English DT Editorial Material DE aerospace medicine; education ID SPECIALTY AB GRENON SM, SAARY J. Challenges in aerospace medicine education. Aviat Space Environ Med 2011; 82:1071-2. Aerospace medicine training and research represents a dream for many and a challenge for most. In Canada, although some opportunities exist for the pursuit of education and research in the aerospace medicine field, they are limited despite the importance of this field for enabling safe human space exploration. In this commentary, we aim to identify some of the challenges facing individuals wishing to get involved in the field as well as the causal factors for these challenges. We also explore strategies to mitigate against these. C1 [Grenon, S. Marlene] Univ Calif San Francisco, Dept Surg, Div Vasc & Endovasc Surg, Surg Serv,San Francisco VAMC, San Francisco, CA 94121 USA. [Saary, Joan] Univ Toronto, Dept Occupat & Environm Hlth, Toronto, ON, Canada. RP Grenon, SM (reprint author), Univ Calif San Francisco, Dept Surg, Div Vasc & Endovasc Surg, Surg Serv,San Francisco VAMC, Mail Code 112 G,4150 Clement St, San Francisco, CA 94121 USA. EM marlene.grenon@ucsfmedctr.org NR 8 TC 0 Z9 1 U1 0 U2 3 PU AEROSPACE MEDICAL ASSOC PI ALEXANDRIA PA 320 S HENRY ST, ALEXANDRIA, VA 22314-3579 USA SN 0095-6562 J9 AVIAT SPACE ENVIR MD JI Aviat. Space Environ. Med. PD NOV PY 2011 VL 82 IS 11 BP 1071 EP 1072 DI 10.3357/ASEM.3073.2011 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Sport Sciences SC Public, Environmental & Occupational Health; General & Internal Medicine; Sport Sciences GA 837DZ UT WOS:000296172600011 PM 22097645 ER PT J AU Winters, M Lloyd, R Shahidi, A Brown, S Holodniy, M AF Winters, Mark Lloyd, Robert, Jr. Shahidi, Azra Brown, Sheldon Holodniy, Mark TI Use of dried clinical samples for storing and detecting influenza RNA SO INFLUENZA AND OTHER RESPIRATORY VIRUSES LA English DT Article DE Dried samples; influenza; real-time PCR ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD SPOT ASSAY; DRUG-RESISTANCE; H1N1 VIRUS; A H1N1; SURVEILLANCE; COLLECTION; AMPLIFICATION; SENSITIVITY; DIAGNOSIS AB Background Most clinical samples collected for diagnostic influenza testing and monitoring require refrigerated or frozen storage or shipment, which imparts logistic and cost burdens. The ability to store and ship dried clinical specimens under ambient conditions for influenza testing would significantly reduce costs and protect samples from improper storage or equipment failure, especially in remote or resource-limited areas. Objectives To evaluate the collection and storage of dried clinical samples on a transport matrix (ViveST (TM), ST) for influenza RNA testing by real-time reverse-transcription PCR (RT-PCR). Methods Viral transport medium from swab or sputum samples was applied to ST, dried, and stored under ambient conditions from 2 days to 6 months. Additional aliquots of samples were frozen. Testing of frozen and ST-stored samples was performed using the WHO/CDC real-time influenza A (H1N1) RT-PCR protocol and compared to the Luminex xTAG RVP assay. Results ST-stored samples yielded slightly higher threshold cycle values (median 2 54 cycles) compared to frozen samples tested in parallel. This difference was consistent regardless of viral input. There was no significant difference in signal recovery between samples stored for 1 week versus samples stored for 3 weeks, or from three samples stored for 6 months. Qualitatively, clinical specimens stored on ST were 100% concordant (36/36) with frozen samples for detecting the presence of influenza A RNA. Conclusion ST-processed dried specimens produced similar rates of seasonal or novel 2009 HIN1 influenza RNA detection compared to conventional sample processing and thus presents a viable alternative to refrigerated or frozen samples. C1 [Winters, Mark; Holodniy, Mark] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Winters, Mark; Holodniy, Mark] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Lloyd, Robert, Jr.] Res ThinkTank Inc, Buford, GA USA. [Shahidi, Azra; Brown, Sheldon] James J Peters VA Med Ctr, Bronx, NY USA. RP Winters, M (reprint author), AIDS Res Ctr, 3801 Miranda Ave 132, Palo Alto, CA 94304 USA. EM mark.winters@stanford.edu NR 33 TC 1 Z9 1 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1750-2640 J9 INFLUENZA OTHER RESP JI Influenza Other Respir. Viruses PD NOV PY 2011 VL 5 IS 6 BP 413 EP 417 DI 10.1111/j.1750-2659.2011.00253.x PG 5 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 836BA UT WOS:000296080300009 PM 21668673 ER PT J AU Bai, XY Ovrutsky, AR Kartalija, M Chmura, K Kamali, A Honda, JR Oberley-Deegan, RE Dinarello, CA Crapo, JD Chang, LY Chan, ED AF Bai, Xiyuan Ovrutsky, Alida R. Kartalija, Marinka Chmura, Kathryn Kamali, Amanda Honda, Jennifer R. Oberley-Deegan, Rebecca E. Dinarello, Charles A. Crapo, James D. Chang, Ling-Yi Chan, Edward D. TI IL-32 expression in the airway epithelial cells of patients with Mycobacterium avium complex lung disease SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cytokine; immunohistochemistry; non-tuberculous mycobacteria ID NECROSIS-FACTOR-ALPHA; A VIRUS-INFECTION; NONTUBERCULOUS MYCOBACTERIA; PROINFLAMMATORY CYTOKINE; INTERFERON-GAMMA; TNF-ALPHA; MACROPHAGE APOPTOSIS; TUBERCULOSIS; IMMUNITY; PREVALENCE AB Lung disease due to Mycobacterium avium complex (MAC) organisms is increasing. A greater understanding of the host immune response to MAC organisms will provide a foundation to develop novel therapies for these recalcitrant infections. IL-32 is a newly described pro-inflammatory cytokine that enhances host immunity against various microbial pathogens. Cytokines that induce IL-32 such as interferon-gamma, IL-18, IL-12 and tumor necrosis factor-alpha are of considerable importance to mycobacterial immunity. We performed immunohistochemistry and morphometric analysis to quantify IL-32 expression in the lungs of 11 patients with MAC lung disease and 10 controls with normal lung tissues. After normalizing for basement membrane length, there was a profound increase in IL-32 expression in the airway epithelial cells of the MAC-infected lungs compared with controls. Following normalization for alveolar surface area, there was a trend toward increased IL-32 expression in type II alveolar cells and alveolar macrophages in the lungs of MAC patients. Human airway epithelial cells (BEAS-2B) infected with M. avium produced IL-32 by a nuclear factor-kappa B-dependent mechanism. In both BEAS-2B cells and human monocyte-derived macrophages, exogenous IL-32 gamma significantly reduced the growth of intracellular M. avium. This finding was corroborated by an increase in the number of intracellular M. avium recovered from THP-1 monocytes silenced for endogenous IL-32 expression. The anti-mycobacterial effect of IL-32 may be due, in part, to increased apoptosis of infected cells. These findings indicate that IL-32 facilitates host defense against MAC organisms but may also contribute to the airway inflammation associated with MAC pulmonary disease. C1 [Bai, Xiyuan; Ovrutsky, Alida R.; Chmura, Kathryn; Oberley-Deegan, Rebecca E.; Crapo, James D.; Chang, Ling-Yi; Chan, Edward D.] Natl Jewish Hlth, Dept Acad Affairs, Denver, CO 80206 USA. [Bai, Xiyuan; Ovrutsky, Alida R.; Kartalija, Marinka; Chan, Edward D.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80220 USA. [Bai, Xiyuan; Ovrutsky, Alida R.; Honda, Jennifer R.; Chan, Edward D.] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA. [Kartalija, Marinka; Dinarello, Charles A.] Univ Colorado Denver, Div Infect Dis, Aurora, CO 80045 USA. [Kamali, Amanda; Honda, Jennifer R.; Chan, Edward D.] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA. [Chan, Edward D.] Natl Jewish Hlth, Dept Med, Cell Biol Program, Denver, CO 80206 USA. RP Bai, XY (reprint author), Natl Jewish Hlth, Dept Acad Affairs, 1400 Jackson St, Denver, CO 80206 USA. EM baix@njhealth.org FU Department of Veterans Affairs Veterans Health Administration; Office of Research and Development; National Institutes of Health [AI15614] FX Department of Veterans Affairs Veterans Health Administration, Office of Research and Development (E.D.C.) and National Institutes of Health (AI15614 to C.A.D.). NR 73 TC 11 Z9 12 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 2011 VL 23 IS 11 BP 679 EP 691 DI 10.1093/intimm/dxr075 PG 13 WC Immunology SC Immunology GA 838MG UT WOS:000296295700003 PM 22033195 ER PT J AU Lee, KB Murray, SS Duarte, MEL Spitz, JF Johnson, JS Song, KJ Brochmann, EJ Taghavi, CE Keorochana, G Liao, JC Wang, JC AF Lee, Kwang-Bok Murray, Samuel S. Duarte, M. Eugenia L. Spitz, Juliana F. Johnson, Jared S. Song, Kyung-Jin Brochmann, Elsa J. Taghavi, Cyrus E. Keorochana, Gun Liao, Jen-Chung Wang, Jeffrey C. TI Effects of the Bone Morphogenetic Protein Binding Protein spp24 (Secreted Phosphoprotein 24 kD) on the Growth of Human Lung Cancer Cells SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE spp24; bone morphogenetic proteins; lung cancer; bone tumors; A549 cell line; metastases ID METASTATIC PROSTATE-CANCER; OSTEOLYTIC LESIONS; TUMOR-GROWTH; EXPRESSION; OVEREXPRESSION; ANTAGONISTS; CARCINOMAS; MOUSE AB Bone morphogenetic proteins (BMPs) and transforming growth factor-beta (TGF-beta) contribute to the growth of some skeletal metastases through autocrine stimulation. Secreted phosphoprotein 24 kDa (spp24) has been shown to bind to both BMP-2 and TGF-beta and to markedly inhibit the osteogenic properties of rhBMP-2. We hypothesized that the addition of spp24 would sequester autocrine growth factors (especially BMP-2) and reduce tumor growth in a system (A549 human non-small cell lung cancer cell line) where autocrine stimulation by BMP-2 is known to be important. A549 cells were injected into two sites (subcutaneous and intraosseus) in SCID mice with and without the co-injection of BMP-2 and spp24. Tumor growth after 8 weeks was assessed through gross examination, radiological imaging, and histological analysis. Spp24 attenuated the tumor growth enhancing effects of rhBMP-2 and reduced the tumor growth when added to tumor cells that were not treated with BMP-2. We conclude that spp24 can reduce A549 cell tumor growth in both soft tissue and intraosseus environments. We hypothesize that the mechanism for this inhibition is interruption of autocrine stimulation through the sequestration of BMP-2. Spp24 can be developed into a therapeutic agent that can be employed in clinical situations where the inhibitions of BMPs and related proteins is advantageous. (C) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:1712-1718, 2011 C1 [Lee, Kwang-Bok; Johnson, Jared S.; Taghavi, Cyrus E.; Keorochana, Gun; Liao, Jen-Chung; Wang, Jeffrey C.] Univ Calif Los Angeles, Dept Orthopaed Surg, UCLA Comprehens Spine Ctr, Los Angeles, CA 90095 USA. [Lee, Kwang-Bok; Song, Kyung-Jin] Chonbuk Natl Univ, Sch Med, Chonbuk Natl Univ Hosp, Dept Orthopaed Surg,Res Inst Clin Med, Jonju, South Korea. [Murray, Samuel S.; Brochmann, Elsa J.] VA Greater Los Angeles Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Sepulveda, CA USA. [Murray, Samuel S.; Brochmann, Elsa J.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. [Murray, Samuel S.; Wang, Jeffrey C.] Univ Calif Los Angeles, Biomed Engn Interdept Program, Los Angeles, CA 90095 USA. [Duarte, M. Eugenia L.; Spitz, Juliana F.] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil. [Duarte, M. Eugenia L.; Spitz, Juliana F.] Natl Inst Traumatol & Orthopaed, Rio De Janeiro, Brazil. RP Wang, JC (reprint author), Univ Calif Los Angeles, Dept Orthopaed Surg, UCLA Comprehens Spine Ctr, 1250 16th St,7th Floor,Tower 745, Los Angeles, CA 90095 USA. EM jwang@mednet.ucla FU Department of Veterans Affairs FX Supported in part by the Department of Veterans Affairs. NR 30 TC 9 Z9 9 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD NOV PY 2011 VL 29 IS 11 BP 1712 EP 1718 DI 10.1002/jor.21383 PG 7 WC Orthopedics SC Orthopedics GA 832KO UT WOS:000295803900014 PM 21509819 ER PT J AU Lee, J Zaki, J Harvey, PO Ochsner, K Green, MF AF Lee, J. Zaki, J. Harvey, P. -O. Ochsner, K. Green, M. F. TI Schizophrenia patients are impaired in empathic accuracy SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Empathic accuracy; expressivity; schizophrenia; social cognition ID NATURALISTIC SOCIAL COGNITION; BASES; NEUROSCIENCE AB Background. Empathy is crucial for successful social relationships. Despite its importance for social interactions, little is known about empathy in schizophrenia. This study investigated the degree to which schizophrenia patients can accurately infer the affective state of another person (i.e. empathic accuracy). Method. A group of 30 schizophrenia patients and 22 healthy controls performed an empathic accuracy task on which they continuously rated the affective state of another person shown in a video (referred to as the 'target'). These ratings were compared with the target's own continuous self-rating of affective state; empathic accuracy was defined as the correlation between participants' ratings and the targets' self-ratings. A separate line-tracking task was administered to measure motoric/attentional factors that could account for group differences in performance. Participants' self-rated empathy was measured using the Interpersonal Reactivity Index, and targets' self-rated emotional expressivity was measured using the Berkeley Expressivity Questionnaire. Results. Compared with controls, schizophrenia patients showed lower empathic accuracy although they performed the motoric tracking task at high accuracy. There was a significant group x target expressivity interaction such that patients showed a smaller increase in empathic accuracy with higher levels of emotional expressivity by the target, compared with controls. Patients' empathic accuracy was uncorrelated with self-reported empathy or clinical symptoms. Conclusions. Schizophrenia patients showed lower empathic accuracy than controls, and their empathic accuracy was less influenced by the emotional expressivity of the target. These findings suggest that schizophrenia patients benefit less from social cues of another person when making an empathic judgement. C1 [Lee, J.; Harvey, P. -O.; Green, M. F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Lee, J.; Harvey, P. -O.; Green, M. F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Zaki, J.; Ochsner, K.] Columbia Univ, Dept Psychol, New York, NY 10027 USA. RP Lee, J (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 300 Med Plaza,Room 2261, Los Angeles, CA 90095 USA. EM jungheelee@ucla.edu RI Lee, Junghee/C-5226-2014 OI Lee, Junghee/0000-0001-9567-8700 FU National Institute of Mental Health (NIMH) [MH043292, MH076137]; National Institute on Drug Abuse (NIDA) [DA022541]; Autism Speaks Grant [4787] FX Support for this study came from a National Institute of Mental Health (NIMH) grant (no. MH043292 to M. F. G.), a National Institute on Drug Abuse (NIDA) grant (no. DA022541 to K.O.), a NIMH grant (no. MH076137 to K.O.) and an Autism Speaks Grant (no. 4787 to J.Z.). The authors thank Mark R. McGee, Shelly Crosby and Cory Tripp for assistance in data collection. NR 43 TC 40 Z9 40 U1 3 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD NOV PY 2011 VL 41 IS 11 BP 2297 EP 2304 DI 10.1017/S0033291711000614 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 837XX UT WOS:000296246300006 PM 21524334 ER PT J AU Biczo, G Hegyi, P Dosa, S Shalbuyeva, N Berczi, S Sinervirta, R Hracsko, Z Siska, A Kukor, Z Jarmay, K Venglovecz, V Varga, IS Ivanyi, B Alhonen, L Wittmann, T Gukovskaya, A Takacs, T Rakonczay, Z AF Biczo, Gyoergy Hegyi, Peter Dosa, Sandor Shalbuyeva, Natalia Berczi, Sandor Sinervirta, Riitta Hracsko, Zsuzsanna Siska, Andrea Kukor, Zoltan Jarmay, Katalin Venglovecz, Viktoria Varga, Ilona S. Ivanyi, Bela Alhonen, Leena Wittmann, Tibor Gukovskaya, Anna Takacs, Tamas Rakonczay, Zoltan, Jr. TI The Crucial Role of Early Mitochondrial Injury in L-Lysine-Induced Acute Pancreatitis SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID KAPPA-B ACTIVATION; L-ARGININE; SUPEROXIDE-DISMUTASE; EXCESS LYSINE; RATS; TRYPSINOGEN; PROTEIN; MODEL; MECHANISMS; ANALOGS AB Aims: Large doses of intraperitoneally injected basic amino acids, L-arginine, or L-ornithine, induce acute pancreatitis in rodents, although the mechanisms mediating pancreatic toxicity remain unknown. Another basic amino acid, L-lysine, was also shown to cause pancreatic acinar cell injury. The aim of the study was to get insight into the mechanisms through which L-lysine damages the rat exocrine pancreas, in particular to characterize the kinetics of L-lysine-induced mitochondrial injury, as well as the pathologic responses (including alteration of antioxidant systems) characteristic of acute pancreatitis. Results: We showed that intraperitoneal administration of 2 g/kg L-lysine induced severe acute necrotizing pancreatitis. L-lysine administration caused early pancreatic mitochondrial damage that preceded the activation of trypsinogen and the proinflammatory transcription factor nuclear factor-kappa B (NF-kappa B), which are commonly thought to play an important role in the development of acute pancreatitis. Our data demonstrate that L-lysine impairs adenosine triphosphate synthase activity of isolated pancreatic, but not liver, mitochondria. Innovation and Conclusion: Taken together, early mitochondrial injury caused by large doses of L-lysine may lead to the development of acute pancreatitis independently of pancreatic trypsinogen and NF-kappa B activation. Antioxid. Redox Signal. 15, 2669-2681. C1 [Biczo, Gyoergy; Hegyi, Peter; Jarmay, Katalin; Wittmann, Tibor; Takacs, Tamas; Rakonczay, Zoltan, Jr.] Univ Szeged, Dept Med 1, H-6701 Szeged, Hungary. [Dosa, Sandor; Berczi, Sandor; Ivanyi, Bela] Univ Szeged, Dept Pathol, H-6701 Szeged, Hungary. [Shalbuyeva, Natalia; Gukovskaya, Anna] Univ Calif Los Angeles, Los Angeles, CA USA. [Shalbuyeva, Natalia; Gukovskaya, Anna] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Sinervirta, Riitta; Alhonen, Leena] Univ Eastern Finland, AI Virtanen Inst Mol Sci, Bioctr Kuopio, Kuopio, Finland. [Hracsko, Zsuzsanna; Varga, Ilona S.] Univ Szeged, Dept Biochem & Mol Biol, H-6701 Szeged, Hungary. [Siska, Andrea] Univ Szeged, Dept Clin Chem, H-6701 Szeged, Hungary. [Kukor, Zoltan] Semmelweis Univ, Dept Med Chem Mol Biol & Pathobiochem, Budapest, Hungary. [Venglovecz, Viktoria] Univ Szeged, Dept Pharmacol & Pharmacotherapy, H-6701 Szeged, Hungary. RP Rakonczay, Z (reprint author), Univ Szeged, Dept Med 1, POB 427, H-6701 Szeged, Hungary. EM raz@in1st.szote.u-szeged.hu FU National Development Agency [TAMOP-4.2.2-08/1/2008-0002, 0013, TAMOP-4.2.1.B-09/1/KONV-2010-0005]; Hungarian Scientific Research Fund [K78311, NNF 78851, PD78087]; Hungarian Academy of Sciences [BO 00334/08/5, BO 00174/10/5]; Academy of Finland [130087] FX This study was supported by National Development Agency grants (TAMOP-4.2.2-08/1/2008-0002 and 0013; TAMOP-4.2.1.B-09/1/KONV-2010-0005), the Hungarian Scientific Research Fund (K78311 to Z.R., NNF 78851 to P.H., and PD78087 to V.V.), the Hungarian Academy of Sciences (BO 00334/08/5 to P.H. and BO 00174/10/5 to Z.R.), and the Academy of Finland (130087 to L.A.). The authors would like to thank Dr. Gizella Karacsony for her help with the TUNEL assay. The rabbit anti-HSP72 antibody was a generous gift from Dr. Istvan Kurucz. NR 31 TC 13 Z9 14 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD NOV PY 2011 VL 15 IS 10 BP 2669 EP 2681 DI 10.1089/ars.2011.4065 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 831MF UT WOS:000295734400003 PM 21644850 ER PT J AU Gukovsky, I Pandol, SJ Gukovskaya, AS AF Gukovsky, Ilya Pandol, Stephen J. Gukovskaya, Anna S. TI Organellar Dysfunction in the Pathogenesis of Pancreatitis SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID MITOCHONDRIAL PERMEABILITY TRANSITION; CYTOCHROME-C RELEASE; SMALL-MOLECULE INHIBITORS; BCL-X-L; CELL-DEATH; ACINAR-CELLS; OXIDATIVE STRESS; MEMBRANE PERMEABILIZATION; TRYPSINOGEN ACTIVATION; CASPASE ACTIVATION AB Significance: Acute pancreatitis is an inflammatory disease of exocrine pancreas that carries considerable morbidity and mortality; its pathophysiology remains poorly understood. During the past decade, new insights have been gained into signaling pathways and molecules that mediate the inflammatory response of pancreatitis and death of acinar cells (the main exocrine pancreas cell type). By contrast, much less is known about the acinar cell organellar damage in pancreatitis and how it contributes to the disease pathogenesis. Recent Advances: This review summarizes recent findings from our group, obtained on experimental in vivo and ex vivo models, which reveal disordering of key cellular organelles, namely, mitochondria, autophagosomes, and lysosomes, in pancreatitis. Our results indicate a critical role for mitochondrial permeabilization in determining the balance between apoptosis and necrosis in pancreatitis, and thus the disease severity. We further investigate how the mitochondrial dysfunction (and hence acinar cell death) is regulated by Ca(2+), reactive oxygen species, and BclxL, in relation to specific properties of pancreatic mitochondria. Our results also reveal that autophagy, the principal cellular degradative, lysosome-driven pathway, is impaired in pancreatitis due to inefficient lysosomal function, and that impaired autophagy mediates two key pathological responses of pancreatitis-accumulation of vacuoles in acinar cells and the abnormal, intra-acinar activation of digestive enzymes such as trypsinogen. Critical Issues and Future Directions: The findings discussed in this review indicate critical roles for mitochondrial and autophagic/lysosomal dysfunctions in the pathogenesis of pancreatitis and delineate directions for detailed investigations into the molecular events that underlie acinar cell organellar damage. Antioxid. Redox Signal. 15, 2699-2710. C1 [Gukovsky, Ilya; Pandol, Stephen J.; Gukovskaya, Anna S.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Gukovsky, I (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM igukovsk@ucla.edu; agukovsk@ucla.edu FU NIH [DK59936, AA19730] FX Department of Veterans Affairs; NIH R01 grants DK59936 and AA19730; Southern California Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis (NIH P50AA11999). NR 92 TC 25 Z9 27 U1 0 U2 10 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD NOV PY 2011 VL 15 IS 10 BP 2699 EP 2710 DI 10.1089/ars.2011.4068 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 831MF UT WOS:000295734400005 PM 21834686 ER PT J AU Fish, KN Sweet, RA Lewis, DA AF Fish, Kenneth N. Sweet, Robert A. Lewis, David A. TI Differential Distribution of Proteins Regulating GABA Synthesis and Reuptake in Axon Boutons of Subpopulations of Cortical Interneurons SO CEREBRAL CORTEX LA English DT Article DE cannabinoid 1 receptor; GABA; GABA membrane transporter 1; glutamic acid decarboxylase; parvalbumin ID GLUTAMIC-ACID DECARBOXYLASE; GAMMA-AMINOBUTYRIC-ACID; MONKEY PREFRONTAL CORTEX; CANNABINOID CB1 RECEPTOR; GAD(67) MESSENGER-RNAS; RAT SPINAL-CORD; POSTNATAL-DEVELOPMENT; 2 FORMS; MONOCLONAL-ANTIBODIES; TRANSIENT INCREASE AB Subclasses of gamma-aminobutyric acid (GABA) interneurons differentially influence cortical network activity. The contribution of differences in GABA synthesis and reuptake in axon boutons to cell type-specific functions is unknown. GABA is synthesized within boutons by glutamic acid decarboxylase 65 (GAD65) and GAD67, while GAT1 is responsible for GABA reuptake. Using an imaging methodology capable of determining the colocalization frequency of different immunocytochemical labels in the same bouton and the quantification of the fluorescence intensity of each label in these same structures, we assessed the bouton levels of GAD65, GAD67, and GAT1 in parvalbumin-expressing chandelier (PV(ch)) and basket (PV(b)) neurons and cannabinoid 1 receptor-expressing basket (CB1r(b)) neurons in the monkey prefrontal cortex. We show that PV(ch) boutons almost exclusively contained GAD67, relative to GAD65, whereas CB1r(b) boutons contained mostly GAD65. In contrast, both GAD65 and GAD67 were easily detected in PV(b) boutons. Furthermore, in comparison with PV(ch) boutons, CB1r(b) boutons expressed low to undetectable levels of GAT1. Our findings provide a new basis for the distinctive functional roles of these perisomatic-innervating interneurons in cortical circuits. In addition, they strongly suggest that altered levels of GAD67 or GAD65, as seen in some psychiatric diseases, would have cell type-specific consequences on the modulation of GABA neurotransmission. C1 [Fish, Kenneth N.] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Translat Neurosci Program, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN MIRECC 4, Pittsburgh, PA 15206 USA. [Lewis, David A.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15213 USA. RP Fish, KN (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Translat Neurosci Program, Biomed Sci Tower,Room E1652,3811 OHara St, Pittsburgh, PA 15213 USA. EM fishkn@upmc.edu RI Lewis, David/G-4053-2014 OI Lewis, David/0000-0002-3225-6778 FU National Institutes of Health [MH051234, MH084053, MH071533, MH085108]; BMS foundation; Bristol-Myers Squibb; Curridium Ltd; Pfizer FX This work was supported by the National Institutes of Health (grant numbers MH051234 and MH084053 to D. A. L., MH071533 to R. A. S., MH085108 to K.N.F.).; Conflict of Interest: D. A. L. currently receives investigator-initiated research support from the BMS foundation, Bristol-Myers Squibb, Curridium Ltd, and Pfizer and in 2007-2009 served as a consultant in the areas of target identification and validation, and new compound development to AstraZeneca, BioLine RX, Bristol-Myers Squibb, Hoffman-Roche, Lilly, Merck, Neurogen, and SK Life Science. All other authors report no competing interest. NR 56 TC 24 Z9 24 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD NOV PY 2011 VL 21 IS 11 BP 2450 EP 2460 DI 10.1093/cercor/bhr007 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 827FK UT WOS:000295413200003 PM 21422269 ER PT J AU Li, YX Tafti, BA Shaba, W Berenji, GR AF Li, Yuxin Tafti, Bashir A. Shaba, Wisam Berenji, Gholam R. TI Superscan Pattern of F-18 Sodium Fluoride PET/CT Study in a Case of Prostate Cancer SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE F-18 fluoride; superscan; positron emission tomography; bone scan; prostate cancer ID BONE-SCAN; DISEASE; ABSENT AB A 63-year-old man with a history of prostate cancer (Gleason score, 9/10) received brachytherapy 2 years ago. The patient had been diagnosed with bone metastases 7 months ago and received treatment with dexamethasone and flutamide. Recently, the patient complained of worsening bone pain with rapid rising of prostate-specific antigen from 45 to 189. F-18 sodium fluoride PET/CT bone scan was conducted to evaluate for progression of bone metastases. Review of the PET/CT images demonstrated a "superscan" pattern of bone metastases with extensive sodium fluoride uptake in the axial skeleton, and poor visualization of distal appendicular skeleton and kidneys. 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 8 TC 5 Z9 5 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 NOV PY 2011 VL 36 IS 11 BP 1046 EP 1048 DI 10.1097/RLU.0b013e3182291c3d PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 833GV UT WOS:000295871900028 PM 21975402 ER PT J AU Kim, S Lewis, C Nadel, JA AF Kim, Suil Lewis, Courtney Nadel, Jay A. TI Epidermal growth factor receptor reactivation induced by E-prostanoid-3 receptor- and tumor necrosis factor-alpha-converting enzyme-dependent feedback exaggerates interleukin-8 production in airway cancer (NCI-H292) cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Epidermal growth factor receptor; Cyclooxygenase-2; Prostaglandin E2; E-prostanoid-3 receptor; Interleukin-8; Positive feedback ID BRONCHIAL EPITHELIAL-CELLS; PROSTAGLANDIN E-2; HUMAN-LUNG; PROSTANOID RECEPTORS; SIGNALING CASCADE; CIGARETTE-SMOKE; EGF RECEPTOR; EXPRESSION; ACTIVATION; LINES AB Airway epithelial cancer cells produce increased amounts of the chemokine interleukin-8 (IL-8), inducing pro-tumor responses. Multiple stimuli induce airway epithelial IL-8 production epidermal growth factor receptor (EGFR) dependently, but the mechanisms that exaggerate IL-8 production in airway cancers remain unknown. Here we show that direct activation of EGFR (EGFR-P) by its ligand transforming growth factor (TGF)-alpha induces a second EGFR-P in human airway (NCI-H292) cancer cells but not in normal human bronchial epithelial (NHBE) cells, exaggerating IL-8 production in these cancer cells. The second EGFR-P in NCI-H292 cells was caused by metalloprotease INF-alpha-converting enzyme (TACE)-dependent cleavage of EGFR pro-ligands and was responsible for most of the total IL-8 induced by TGF-alpha. In NCI-H292 cells, TGF-alpha induced cyclooxygenase (COX)-2-dependent prostaglandin (PG)E2 production and release. PGE2 increased the second EGFR-P and IL-8 production via binding to its Gi-protein-coupled E-prostanoid (EP)3 receptor. In NHBE cells, TGF-alpha-induced EGFR-P did not lead to PGE2 production or to a second EGFR-P, and less IL-8 was produced. Thus, we conclude that a positive feedback pathway involving COX-2/PGE2/EP3 receptor-dependent EGFR reactivation exaggerates IL-8 production in NCI-H292 cancer cells but not in NHBE (normal) cells. Published by Elsevier Inc. C1 [Kim, Suil; Lewis, Courtney; Nadel, Jay A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Kim, Suil; Lewis, Courtney; Nadel, Jay A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Nadel, Jay A.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. RP Kim, S (reprint author), Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,Mailcode R&D 6, Portland, OR 97239 USA. EM kimsui@ohsu.edu; courtney.lewis@ucsf.edu; jay.nadel@ucsf.edu FU National Institutes of Health [HL073906]; American Lung Association; UCSF; Cystic Fibrosis Foundation; Cardiovascular Research Institute FX We thank Dr. Jonathan Koff for his generous advice and for stimulating discussions. This work was supported by National Institutes of Health Grant HL073906 (SK), American Lung Association Biomedical Research Award (SK), UCSF Clinical and Translational Sciences Pilot Research Award (SK), Cystic Fibrosis Foundation Pilot Research Award (SK), and by Cardiovascular Research Institute funding (JAN). NR 44 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 1 PY 2011 VL 317 IS 18 BP 2650 EP 2660 DI 10.1016/j.yexcr.2011.08.023 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 833UA UT WOS:000295909200010 PM 21925169 ER PT J AU Pastor, R Reed, C Burkhart-Kasch, S Li, N Sharpe, AL Coste, SC Stenzel-Poore, MP Phillips, TJ AF Pastor, Raul Reed, Cheryl Burkhart-Kasch, Sue Li, Na Sharpe, Amanda L. Coste, Sarah C. Stenzel-Poore, Mary P. Phillips, Tamara J. TI Ethanol concentration-dependent effects and the role of stress on ethanol drinking in corticotropin-releasing factor type 1 and double type 1 and 2 receptor knockout mice SO PSYCHOPHARMACOLOGY LA English DT Article DE CRF; Stress; Knockout; Alcohol; Drinking; Swim stress ID ALCOHOL-DRINKING; INDUCED INCREASES; CENTRAL NUCLEUS; ANIMAL-MODELS; C57BL/6J MICE; RAT-BRAIN; CRF; ANTAGONIST; ANXIETY; WITHDRAWAL AB Exposure to stressors promotes ethanol (EtOH) consumption and enhances drug craving during abstinence. Corticotropin-releasing factor (CRF), and in particular, CRF actions via type 1 CRF receptors (CRF(1)) are critical in behavioral responses to stressors. CRF(1) play a role in EtOH-induced behavioral neuroadaptation, in binge-like EtOH consumption, and in heightened EtOH consumption in dependent animals. We investigated the involvement of CRF(1) in swim-stress-induced changes in EtOH consumption and in baseline consumption as a function of EtOH concentration. The role of CRF(2) in adapting to effects of the stressor was also examined. Wild-type mice and knockout mice lacking CRF(1) were tested for two-bottle choice EtOH consumption at concentrations of 3-20%. Also, intake of 10% EtOH was examined in wild-type mice and knockout mice lacking CRF(1), or lacking both CRF(1) and CRF(2), before and after acute or repeated swim stress exposures. EtOH intake was reduced in CRF(1) compared with wild-type mice when presented at a concentration of 20% but not when presented at lower concentrations. No genotype-dependent effects were found for saccharin or quinine drinking. Acute swim stress had no effect, but repeated swim stress resulted in higher levels of EtOH consumption in wild-type mice, compared with both types of knockout mice. Stress effects on EtOH drinking were longer lasting in double knockout mice. These data suggest a prominent role of CRF(1) in stressor-induced changes in EtOH consumption, with involvement of CRF(2) in recovery from stressor effects. C1 [Phillips, Tamara J.] Portland VA Med Ctr, Res Serv, Portland, OR 97239 USA. [Pastor, Raul; Reed, Cheryl; Burkhart-Kasch, Sue; Li, Na; Sharpe, Amanda L.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Behav Neurosci Dept, Portland, OR 97201 USA. [Pastor, Raul; Reed, Cheryl; Burkhart-Kasch, Sue; Li, Na; Sharpe, Amanda L.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97201 USA. [Coste, Sarah C.; Stenzel-Poore, Mary P.] Oregon Hlth & Sci Univ, Mol Microbiol & Immunol Dept, Portland, OR 97201 USA. [Pastor, Raul] Univ Jaume 1, Area Psicobiol, Castellon de La Plana, Spain. RP Phillips, TJ (reprint author), Portland VA Med Ctr, Res Serv, R&D32,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM phillipt@ohsu.edu FU Department of Veterans Affairs; NIH from the National Institute of Alcohol Abuse and Alcoholism [R01AA13331, P60AA010760]; NIH from Mental Health [R01MH65689] FX This work was supported by a grant from the Department of Veterans Affairs and NIH grants from the National Institute of Alcohol Abuse and Alcoholism (R01AA13331 and P60AA010760) and from Mental Health (R01MH65689). NR 47 TC 10 Z9 10 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2011 VL 218 IS 1 SI SI BP 169 EP 177 DI 10.1007/s00213-011-2284-6 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 833EP UT WOS:000295865000015 PM 21487655 ER PT J AU Clark, DG AF Clark, David Glenn CA Alzheimer Dis Neuroimaging Initiat TI Residual vectors for Alzheimer disease diagnosis and prognostication SO BRAIN AND BEHAVIOR LA English DT Article DE ADNI; Alzheimer disease; Bioinformatics; Mild cognitive impairment; PET scan AB Alzheimer disease (AD) is an increasingly prevalent neurodegenerative condition and a looming socioeconomic threat. A biomarker for the disease could make the process of diagnosis easier and more accurate, and accelerate drug discovery. The current work describes amethod for scoring brain images that is inspired by fundamental principles from information retrieval (IR), a branch of computer science that includes the development of Internet search engines. For this research, a dataset of 254 baseline 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) scans was obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). For a given contrast, a subset of scans (nine of every 10) was used to compute a residual vector that typified the difference, at each voxel, between the two groups being contrasted. Scans that were not used for computing the residual vector (the remaining one of 10 scans) were then compared to the residual vector using a cosine similarity metric. This process was repeated sequentially, each time generating cosine similarity scores on 10% of the FDG-PET scans for each contrast. Statistical analysis revealed that the scores were significant predictors of functional decline as measured by the Functional Activities Questionnaire (FAQ). When logistic regression models that incorporated these scores were evaluated with leave-one-out cross-validation, cognitively normal controls were discerned from AD with sensitivity and specificity of 94.4% and 84.8%, respectively. Patients who converted from mild cognitive impairment (MCI) to AD were discerned from MCI nonconverters with sensitivity and specificity of 89.7% and 62.9%, respectively, when FAQ scores were brought into the model. Residual vectors are easy to compute and provide a simple method for scoring the similarity between an FDG-PET scan and sets of examples from a given diagnostic group. The method is readily generalizable to any imaging modality. Further interdisciplinary work between IR and clinical neuroscience is warranted. C1 [Clark, David Glenn] Birmingham VA Med Ctr, Birmingham, AL USA. [Clark, David Glenn] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. RP Clark, DG (reprint author), 1720 7th Ave South,SC 620C, Birmingham, AL 35294 USA. EM dgclark@uab.edu FU Department of Veterans Affairs [E6553W]; ADNI (National Institutes of Health) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; NIH [P30 AG010129, K01 AG030514]; Dana Foundation FX Dr. Clark is supported by a Career Development Award from the Department of Veterans Affairs (E6553W), entitled "Semantic Memory, Financial Capacity, and Brain Perfusion in MCI."; Data collection and sharing for this project were funded by the 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, Glax-oSmithKline, 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., as well as 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 23 TC 4 Z9 4 U1 2 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2162-3279 J9 BRAIN BEHAV JI Brain Behav. PD NOV PY 2011 VL 1 IS 2 BP 142 EP 152 DI 10.1002/brb3.19 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA V35UO UT WOS:000209173700010 PM 22399094 ER PT J AU Hogan, TP Wakefield, B Nazi, KM Houston, TK Weaver, FM AF Hogan, Timothy P. Wakefield, Bonnie Nazi, Kim M. Houston, Thomas K. Weaver, Frances M. TI Promoting Access Through Complementary eHealth Technologies: Recommendations for VA's Home Telehealth and Personal Health Record Programs SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE eHealth; patient-centered medical home; telehealth; personal health records; veteran AB BACKGROUND: Many healthcare organizations have embraced eHealth technologies in their efforts to promote patient-centered care, increase access to services, and improve outcomes. OBJECTIVE: Using the Department of Veterans Affairs (VA) as a case study, this paper presents two specific eHealth technologies, the Care Coordination Home Telehealth (CCHT) Program and the My HealtheVet (MHV) personal health record (PHR) portal with integrated secure messaging, and articulates a vision of how they might be implemented as part of a patient-centric healthcare model and used in a complementary manner to enhance access to care and to support patient-centered care. METHODS: Based on our experience and ongoing work with both programs, we offer a series of recommendations for pursuing and ultimately achieving this vision. CONCLUSION: VA's CCHT and MHV programs are examples of an expanding repertoire of eHealth applications available to patients and healthcare teams. VA's new patient-centric healthcare model represents a significant shift in the way that services are delivered and a profound opportunity to incorporate eHealth technologies like the CCHT and MHV programs into clinical practice to increase access to care, and to ensure the responsiveness of such technologies to the preferences and circumstances of patients. C1 [Hogan, Timothy P.; Weaver, Frances M.] Jr VA Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Hogan, Timothy P.; Weaver, Frances M.] Jr VA Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL 60141 USA. [Hogan, Timothy P.; Wakefield, Bonnie; Houston, Thomas K.; Weaver, Frances M.] Edith Nourse Rogers Mem Vet Hosp, eHlth Qual Enhancement Res Initiat, Natl eHlth QUERI Coordinating Ctr, Bedford, MA USA. [Hogan, Timothy P.; Weaver, Frances M.] Loyola Univ Chicago, Program Hlth Serv Res, Stritch Sch Med, Loyola Univ Hlth Syst, Maywood, IL USA. [Wakefield, Bonnie] Iowa City VA Med Ctr, VA Hlth Serv Res & Dev, Ctr Comprehens Access & Delivery Res & Evaluat CA, Iowa City, IA USA. [Nazi, Kim M.] US Dept Vet Affairs, Vet & Consumers Hlth Informat Off, Off Hlth Informat, Vet Hlth Adm, Washington, DC USA. [Houston, Thomas K.] Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res CHQOER, Bedford, MA USA. [Houston, Thomas K.] Univ Massachusetts, Sch Med, Div Hlth Informat & Implementat Sci, Worcester, MA USA. RP Hogan, TP (reprint author), Jr VA Hosp, Ctr Management Complex Chron Care, Edward Hines, 5000 S 5th Ave, Hines, IL 60141 USA. EM timothy.hogan@va.gov NR 59 TC 20 Z9 20 U1 2 U2 4 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 NOV PY 2011 VL 26 SU 2 BP S628 EP S635 DI 10.1007/s11606-011-1765-y PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JP UT WOS:000208812600003 PM 21989614 ER PT J AU Jackson, GL Krein, SL Alverson, DC Darkins, AW Gunnar, W Harada, ND Helfrich, CD Houston, TK Klobucar, TF Nazi, KM Poropatich, RK Ralston, JD Bosworth, HB AF Jackson, George L. Krein, Sarah L. Alverson, Dale C. Darkins, Adam W. Gunnar, William Harada, Nancy D. Helfrich, Christian D. Houston, Thomas K. Klobucar, Thomas F. Nazi, Kim M. Poropatich, Ronald K. Ralston, James D. Bosworth, Hayden B. TI Defining Core Issues in Utilizing Information Technology to Improve Access: Evaluation and Research Agenda SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE access to care; medical informatics; veterans AB The Department of Veterans Affairs (VA) has been at the vanguard of information technology (IT) and use of comprehensive electronic health records. Despite the widespread use of health IT in the VA, there are still a variety of key questions that need to be answered in order to maximize the utility of IT to improve patient access to quality services. This paper summarizes the potential of IT to enhance healthcare access, key gaps in current evidence linking IT and access, and methodologic challenges for related research. We also highlight four key issues to be addressed when implementing and evaluating the impact of IT interventions on improving access to quality care: 1) Understanding broader needs/perceptions of the Veteran population and their caregivers regarding use of IT to access healthcare services and related information. 2) Understanding individual provider/clinicianneeds/perceptions regarding use of IT for patient access to healthcare. 3) System/Organizational issues within the VA and other organizations related to the use of IT to improve access. 4) IT integration and information flow with non-VA entities. While the VA is used as an example, the issues are salient for healthcare systems that are beginning to take advantage of IT solutions. C1 [Jackson, George L.; Bosworth, Hayden B.] Durham Vet Affairs Med Ctr, Hlth Serv Res & Dev HSR& D Ctr Hlth Serv Res Prim, Durham, NC 27705 USA. [Jackson, George L.; Bosworth, Hayden B.] Duke Univ, Med Ctr, Div Gen Internal Med, Durham, NC 27710 USA. [Krein, Sarah L.] Ann Arbor Vet Affairs Med Ctr, HSR & D Ctr Clin Management Res, Ann Arbor, MI USA. [Krein, Sarah L.] Univ Michigan, Sch Med, Div Gen Med, Ann Arbor, MI USA. [Alverson, Dale C.] Univ New Mexico, Hlth Sci Ctr, Ctr Telehealth & Cybermed Res, Albuquerque, NM 87131 USA. [Darkins, Adam W.] Vet Hlth Adm, Off Care Coordinat Serv, Washington, DC USA. [Gunnar, William] Vet Hlth Adm, Off Patient Care Serv, Washington, DC USA. [Harada, Nancy D.] Veteran Affairs Greater Los Angeles Healthcare Sy, Off Grad Med Educ & Geriatr Res, Educ & Clin Ctr, Los Angeles, CA USA. [Harada, Nancy D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Helfrich, Christian D.] Vet Affairs Puget Sound Hlth Care Syst, HSR & D Northwest Outcomes Res Older Adults, Seattle, WA USA. [Helfrich, Christian D.; Ralston, James D.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Houston, Thomas K.] Edith Nourse Rogers Mem Vet Hosp, HSR & D Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Houston, Thomas K.] Univ Massachusetts, Sch Med, Dept Qualitat Hlth Sci, Worcester, MA USA. [Klobucar, Thomas F.] Cent Reg, Vet Rural Hlth Resource Ctr, Iowa City, IA USA. [Nazi, Kim M.] Vet Hlth Adm, Vet & Consumers Hlth Informat Off, Off Hlth Informat, Washington, DC USA. [Poropatich, Ronald K.] Telemed & Adv Technol Res Ctr, Ft Detrick, MD USA. [Ralston, James D.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA. RP Jackson, GL (reprint author), Durham Vet Affairs Med Ctr, Hlth Serv Res & Dev HSR& D Ctr Hlth Serv Res Prim, Durham, NC 27705 USA. EM george.l.jackson@duke.edu RI Krein, Sarah/E-2742-2014; Helfrich, Christian/D-2382-2016 OI Krein, Sarah/0000-0003-2111-8131; Helfrich, Christian/0000-0002-9827-4768 FU VA HSR&D Career Scientist Award [08-027] FX This paper summarizes deliberations of the Adoption and Implementation of IT Workgroup at the VA Health Services Research & Development (HSR&D) State of the Art Conference on Improving Access to VA Care held September 21-22 2010 in Arlington, VA. In addition to the authors, the following individuals were part of the workgroup: Leigh Anderson, MD; David Atkins, MD, MPH; Nancy Maher, Ph.D.; Kevin Vigilante, MD, MPH; and Kenneth R. Wingart, Ph.D. The last author was supported by a VA HSR&D Career Scientist Award (08-027). NR 50 TC 7 Z9 7 U1 5 U2 11 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 NOV PY 2011 VL 26 SU 2 BP S623 EP S627 DI 10.1007/s11606-011-1789-3 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JP UT WOS:000208812600002 PM 21989613 ER PT J AU Kramer, BJ Jouldjian, S Wang, MM Dang, J Mitchell, MN Finke, B Saliba, D AF Kramer, B. Josea Jouldjian, Stella Wang, Mingming Dang, Jeff Mitchell, Michael N. Finke, Bruce Saliba, Debra TI Do Correlates of Dual Use by American Indian and Alaska Native Veterans Operate Uniformly Across the Veterans Health Administration and the Indian Health Service? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE access; underserved populations; health services research AB OBJECTIVE: To determine if the combined effects of patient-level (demographic and clinical characteristics) and organizational-level (structure and strategies to improve access) factors are uniformly associated with utilization of Indian Health Service (IHS) and/or Veterans Health Administration (VHA) by American Indian and Alaska Native (AIAN) Veterans to inform policy which promotes dual use. METHODS: We estimated correlates and compared two separate multilevel logistic regression models of VHA-IHS dual versus IHS-only and VHA-IHS dual versus VHA-only in a sample of 18,892 AIAN Veterans receiving care at 201 VHA and IHS facilities during FY02 and FY03. Demographic, diagnostic, eligibility, and utilization data were drawn from administrative records. A survey of VHA and IHS facilities defined availability of services and strategies to enhance access to healthcare for AIAN Veterans. RESULTS: Facility level strategies that are generally associated with enhancing access to healthcare (e. g., population-based services and programs, transportation or co-location) were not significant factors associated with dual use. In both models the common variable of dual use was related to medical need, defined as the number of diagnoses per patient. Other significant demographic, medical need and organizational factors operated in opposing manners. For instance, age increased the likelihood of dual use versus IHS-only but decreased the likelihood of dual use versus VHA-only. CONCLUSIONS: Efforts to enhance access through population-based and consumer-driven strategies may add value but be less important to utilization than availability of healthcare resources needed by this population. Sharing health records and co-management strategies would improve quality of care while policies allow and promote dual use. C1 [Kramer, B. Josea; Jouldjian, Stella; Saliba, Debra] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ Clin Ctr, Sepulveda, CA 91343 USA. [Kramer, B. Josea; Saliba, Debra] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr Med, Los Angeles, CA 90095 USA. [Wang, Mingming; Mitchell, Michael N.; Saliba, Debra] VA Greater Los Angeles Healthcare Syst, Hlth Serv Res Ctr Excellence, Sepulveda, CA USA. [Dang, Jeff] Consulting Measurement Grp Inc, Torrance, CA USA. [Finke, Bruce] Indian Hlth Serv, Nashville, TN USA. [Saliba, Debra] Univ Calif Los Angeles, Jewish Home Borun Ctr Gerontol Res, Los Angeles, CA USA. [Saliba, Debra] RAND Corp, Santa Monica, CA USA. RP Kramer, BJ (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ Clin Ctr, 16111 Plummer St 11E, Sepulveda, CA 91343 USA. EM Josea.Kramer@va.gov FU VA Health Services Research and Development [ACC 03-304] FX This research was supported by a grant from the VA Health Services Research and Development, ACC 03-304. This report presents findings and conclusions of the authors; it does not necessarily reflect the opinions or policies of the Department of Veterans Affairs or the Indian Health Service. An earlier version of this paper was presented in a paper session at the Gerontological Society of America, annual scientific meetings in New Orleans, November 2010. NR 23 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2011 VL 26 SU 2 BP S662 EP S668 DI 10.1007/s11606-011-1834-2 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JP UT WOS:000208812600008 PM 21989619 ER PT J AU Washington, DL Bean-Mayberry, B Riopelle, D Yano, EM AF Washington, Donna L. Bean-Mayberry, Bevanne Riopelle, Deborah Yano, Elizabeth M. TI Access to Care for Women Veterans: Delayed Healthcare and Unmet Need SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE access to care; women veterans; VA healthcare; health services need; health services utilization AB BACKGROUND: Timely access to healthcare is essential to ensuring optimal health outcomes, and not surprisingly, is at the heart of healthcare reform efforts. While the Veterans Health Administration (VA) has made improved access a priority, women veterans still under-utilize VA healthcare relative to men. Eliminating access disparities requires a better understanding of the barriers to care that women veterans' experience. OBJECTIVE: We examined the association of general and veteran-specific barriers on access to healthcare among women veterans. DESIGN AND PARTICIPANTS: Cross-sectional, population-based national telephone survey of 3,611 women veterans. MAIN MEASURE: Delayed healthcare or unmet healthcare need in the prior 12 months. KEY RESULTS: Of women veterans, 19% had delayed healthcare or unmet need, with higher rates in younger age groups (36%, 29%, 16%, 7%, respectively, in 18-34, 35-49, 50-64, and 65-plus age groups; p<0.001). Among those delaying or going without care, barriers that varied by age group were: unaffordable healthcare (63% of 18-34 versus 12% of 65-plus age groups); inability to take off from work (39% of those <50); and transportation difficulties (36% of 65-plus). Controlling for age, race/ethnicity, regular source of care, and health status, being uninsured (OR=6.5; confidence interval [CI] 3.0-14.0), knowledge gaps about VA care (OR=2.1; 95% CI 1.1-4.0), perception that VA providers are not gender-sensitive (OR=2.4; CI 1.2-4.7), and military sexual assault history (OR=2.1; CI 1.1-4.0) predicted delaying or foregoing care, whereas VA use and enrollment priority did not. CONCLUSIONS: Both general and veteran-specific factors impact women veterans' access to needed services. Many of the identified access barriers are potentially modifiable through expanded VA healthcare and social services. Health reform efforts should address these barriers for VA nonusers. Efforts are also warranted to improve women veterans' knowledge of availability and affordability of VA healthcare, and to enhance the gender-sensitivity of this care. C1 [Washington, Donna L.; Bean-Mayberry, Bevanne; Riopelle, Deborah; Yano, Elizabeth M.] VA Greater Los Angeles Hlth Serv Res & Dev HSR &, 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.] Univ Calif Los Angeles, Dept Hlth Serv, ServicesUCLA Sch Publ Hlth, Los Angeles, CA USA. [Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 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 FU Department of Veterans Affairs (VA) Office of Public Health and Environmental Hazards, Women Veterans Health Strategic Healthcare Group; VA Health Services Research and Development (HSRD) Service [SDR-08-270]; VA HSR&D Research Career Scientist award [RCS-05-195]; VA HSR&D Research Career Development Transition award [RCD 02-039] FX This study was funded by the Department of Veterans Affairs (VA) Office of Public Health and Environmental Hazards, Women Veterans Health Strategic Healthcare Group, and the VA Health Services Research and Development (HSR&D) Service (#SDR-08-270). Dr. Yano is supported by a VA HSR&D Research Career Scientist award (#RCS-05-195). Dr. Bean-Mayberry was supported by a VA HSR&D Research Career Development Transition award (#RCD 02-039) during this study. Dr. Washington had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors gratefully acknowledge Mark Canning for project management, Julia Yosef, MA for assistance with survey fieldwork, Su Sun, MPH for assistance with data management, and Michael Mitchell, PhD, for statistical assistance. The views expressed within are solely those of the authors, and do not necessarily represent the views of the Department of Veterans Affairs or the United States government. NR 30 TC 51 Z9 51 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2011 VL 26 SU 2 BP S655 EP S661 DI 10.1007/s11606-011-1772-z PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JP UT WOS:000208812600007 PM 21989618 ER PT J AU Khodyakov, D Stockdale, S Jones, F Ohito, E Jones, A Lizaola, E Mango, J AF Khodyakov, Dmitry Stockdale, Susan Jones, Felica Ohito, Elizabeth Jones, Andrea Lizaola, Elizabeth Mango, Joseph TI An Exploration of the Effect of Community Engagement in Research on Perceived Outcomes of Partnered Mental Health Services Projects SO SOCIETY AND MENTAL HEALTH LA English DT Article DE CBPR; community-based mental health; mental health; community engagement in research; community-academic partnerships AB Mental health research projects address sensitive issues for vulnerable populations and are implemented in complex environments. Community-based participatory research approaches are recommended for health research on vulnerable populations, but little is known about how variation in participation affects outcomes of partnered research projects. We developed a conceptual model demonstrating the impact of community engagement in research on outcomes of partnered projects. We collected data on key constructs from community and academic leaders of 21 sampled partnered research projects in two cycles of a research center funded by the National Institute of Mental Health. We conducted empirical analyses to test the model. Our findings suggest that community engagement in research is positively associated with perceived professional development as well as political and community impact. C1 [Khodyakov, Dmitry] RAND Corp, Santa Monica, CA 90407 USA. [Stockdale, Susan] US Dept Vet Affairs, Los Angeles, CA USA. [Stockdale, Susan; Lizaola, Elizabeth; Mango, Joseph] Univ Calif Los Angeles, Los Angeles, CA USA. [Jones, Felica; Jones, Andrea] Hlth African Amer Families, Los Angeles, CA USA. [Ohito, Elizabeth] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Jones, Andrea] Charles Drew Univ Med & Sci, Los Angeles, CA USA. RP Khodyakov, D (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA. EM dkhodyak@rand.org FU NIMH NIH HHS [P30 MH068639, P30 MH068639-05, P30 MH082760, P30 MH082760-01] NR 45 TC 11 Z9 11 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2156-8693 EI 2156-8731 J9 SOC MENT HEALTH JI Soc. Ment. Health PD NOV PY 2011 VL 1 IS 3 BP 185 EP 199 DI 10.1177/2156869311431613 PG 15 WC Sociology SC Sociology GA V36AA UT WOS:000209184800004 PM 22582144 ER PT J AU Hoyer, D Boyko, E McNeely, M Leonetti, D Kahn, S Fujimoto, W AF Hoyer, D. Boyko, E. J. McNeely, M. J. Leonetti, D. L. Kahn, S. E. Fujimoto, W. Y. TI Subcutaneous thigh fat area is unrelated to risk of type 2 diabetes in a prospective study of Japanese Americans SO DIABETOLOGIA LA English DT Article DE Adiposity; Computed tomography; Diabetes mellitus; Epidemiology; Japanese American; Prospective study; Thigh circumference; Thigh subcutaneous fat; Visceral fat; Waist circumference ID ADIPOSE-TISSUE DISTRIBUTION; IMPAIRED GLUCOSE-TOLERANCE; BODY-FAT; POSTMENOPAUSAL WOMEN; INSULIN-RESISTANCE; MEN; OBESE; MASS; DYSLIPIDEMIA; ASSOCIATIONS AB Cross-sectional research has reported a negative association between subcutaneous thigh fat (STF) and type 2 diabetes prevalence but no prospective research on this association exists using direct measurements of STF obtained from imaging studies while adjusting for other fat depots. We studied the independent associations of intra-abdominal fat (IAF), subcutaneous abdominal fat (SAF) and STF with future risk of diabetes. We prospectively followed 489 non-diabetic Japanese Americans (BMI 25.0-29.9 kg/m(2) 32.7%, a parts per thousand yen30.0 kg/m(2) 5.4%) over 10 years for the development of diabetes defined by use of hypoglycaemic medication or a fasting plasma glucose a parts per thousand yen7.0 mmol/l or 2 h a parts per thousand yen11.1 mmol/l during an OGTT. STF, SAF and IAF area were measured by computed tomography scan and mid-thigh circumference (TC) by tape measure at baseline. Over 10 years, 103 people developed diabetes. STF area was not independently associated with the odds of developing diabetes in a univariate or multiple logistic regression model (OR for a 1 SD increase 0.8 [95% CI 0.5, 1.2]) adjusted for age, sex, BMI, IAF and SAF. The only fat depot associated with diabetes odds in this model was IAF. TC was borderline significantly associated with a lower odds of developing diabetes (0.7 [95% CI 0.5, 1.0], p = 0.052). Similar to other research, TC was negatively associated with diabetes risk, whereas STF was not, arguing that the negative association between TC and diabetes observed in other research is not due to STF mass. IAF area emerged as the only measured fat depot that was independently associated with type 2 diabetes risk. C1 [Boyko, E. J.; Kahn, S. E.] VA Puget Sound Hlth Care Syst, Seattle, WA 98101 USA. [Hoyer, D.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Boyko, E. J.; McNeely, M. J.; Kahn, S. E.; Fujimoto, W. Y.] Univ Washington, Dept Med, Seattle, WA USA. [Leonetti, D. L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Boyko, E (reprint author), VA Puget Sound Hlth Care Syst, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM eboyko@uw.edu OI Kahn, Steven/0000-0001-7307-9002; Boyko, Edward/0000-0002-3695-192X FU National Institutes of Health [DK-31170, HL-49293, DK-02654]; VA Puget Sound Health Care System FX This work was supported by National Institutes of Health Grants DK-31170, HL-49293 and DK-02654; by facilities and services provided by the Diabetes and Endocrinology Research Center (DK-17047), Clinical Nutrition Research Unit (DK-35816), and the General Clinical Research Center (RR-00037) at the University of Washington. VA Puget Sound Health Care System provided support for the involvement of E.J. Boyko and S.E. Kahn in this research. We are grateful to the King County Japanese-American community for their support and cooperation. NR 20 TC 7 Z9 7 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 2011 VL 54 IS 11 BP 2795 EP 2800 DI 10.1007/s00125-011-2275-5 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 830TJ UT WOS:000295679800008 PM 21837509 ER PT J AU Hochman, M McCormick, D AF Hochman, Michael McCormick, Danny TI Endpoint Selection and Relative (Versus Absolute) Risk Reporting in Published Medication Trials SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE surrogate endpoints; composite endpoints; disease-specific mortality; relative risk reduction ID RANDOMIZED CONTROLLED-TRIALS; CLINICAL-TRIALS; COMPOSITE OUTCOMES; USERS GUIDES; INTERVENTION; ASSOCIATION; CONCLUSIONS; PREVENTION; BENEFITS; ARTICLE AB The use of surrogate and composite endpoints, disease-specific mortality as an endpoint, and relative (rather than absolute) risk reporting in clinical trials may produce results that are misleading or difficult to interpret. To describe the prevalence of these endpoints and of relative risk reporting in medication trials. We analyzed all randomized medication trials published in the six highest impact general medicine journals between June 1, 2008 and September 30, 2010 and determined the percentage using these endpoints and the percentage reporting results in the abstract exclusively in relative terms. We identified 316 medication trials, of which 116 (37%) used a surrogate primary endpoint and 106 (34%) used a composite primary endpoint. Among 118 trials in which the primary endpoint involved mortality, 32 (27%) used disease-specific mortality rather than all-cause mortality. Among 157 trials with positive results, 69 (44%) reported these results in the abstract exclusively in relative terms. Trials using surrogate endpoints and disease-specific mortality as an endpoint were more likely to be exclusively commercially funded (45% vs. 29%, difference 15% [95% CI 5%-26%], P = 0.004, and 39% vs. 16%, difference 22% [95% CI 6%-37%], P = 0.007, respectively). Trials using surrogate endpoints were more likely to report positive results (66% vs. 49%, difference 17% [95% CI 5%-28%], P = 0.006) while those using mortality endpoints were less likely to be positive (46% vs. 62%, difference -16% [95% CI -27%--4%], P = 0.01). The use of surrogate and composite endpoints, endpoints involving disease-specific mortality, and relative risk reporting is common. Articles should highlight the limitations of these endpoints and should report results in absolute terms. C1 [Hochman, Michael] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90024 USA. [Hochman, Michael] US Dept Vet Affairs, Los Angeles, CA 90024 USA. [McCormick, Danny] Cambridge Hlth Alliance, Dept Med, Cambridge, MA USA. [McCormick, Danny] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hochman, M (reprint author), Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, 911 Broxton Ave,3rd Floor, Los Angeles, CA 90024 USA. EM Meh1979@gmail.com NR 32 TC 3 Z9 3 U1 0 U2 4 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 NOV PY 2011 VL 26 IS 11 BP 1246 EP 1252 DI 10.1007/s11606-011-1813-7 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 830UU UT WOS:000295683500007 PM 21842324 ER PT J AU Bass, MG Korthuis, PT Cofrancesco, J Berkenblit, GV Sullivan, LE Asch, SM Bashook, PG Edison, M Sosman, JM Cook, RL AF Bass, Michael G. Korthuis, P. Todd Cofrancesco, Joseph, Jr. Berkenblit, Gail V. Sullivan, Lynn E. Asch, Steve M. Bashook, Philip G. Edison, Marcia Sosman, James M. Cook, Robert L. TI Provider and Practice Characteristics Associated with Use of Rapid HIV Testing by General Internists SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE testing; rapid HIV testing; HIV/AIDS; general internal medicine physicians; HIV prevention; medical practice setting ID HEALTH-CARE SETTINGS; EMERGENCY-DEPARTMENT; SCREENING-PROGRAM; ROUTINE; PHYSICIANS; VIRUS; RECOMMENDATIONS; ADOLESCENTS; PREVALENCE AB Rapid HIV testing could increase routine HIV testing. Most previous studies of rapid testing were conducted in acute care settings, and few described the primary care providers' perspective. To identify characteristics of general internal medicine physicians with access to rapid HIV testing, and to determine whether such access is associated with differences in HIV-testing practices or perceived HIV-testing barriers. Web-based cross-sectional survey conducted in 2009. A total of 406 physician members of the Society of General Internal Medicine who supervise residents or provide care in outpatient settings. Surveys assessed provider and practice characteristics, HIV-testing types, HIV-testing behavior, and potential barriers to HIV testing. Among respondents, 15% had access to rapid HIV testing. In multivariable analysis, physicians were more likely to report access to rapid testing if they were non-white (OR 0.45, 95% CI 0.22, 0.91), had more years since completing training (OR 1.06, 95% CI 1.02, 1.10), practiced in the northeastern US (OR 2.35; 95% CI 1.28, 4.32), or their practice included a higher percentage of uninsured patients (OR 1.03; 95% CI 1.01, 1.04). Internists with access to rapid testing reported fewer barriers to HIV testing. More respondents with rapid than standard testing reported at least 25% of their patients received HIV testing (51% versus 35%, p = 0.02). However, access to rapid HIV testing was not significantly associated with the estimated proportion of patients receiving HIV testing within the previous 30 days (7.24% vs. 4.58%, p = 0.06). Relatively few internists have access to rapid HIV testing in outpatient settings, with greater availability of rapid testing in community-based clinics and in the northeastern US. Future research may determine whether access to rapid testing in primary care settings will impact routinizing HIV testing. C1 [Cook, Robert L.] Univ Florida, Dept Epidemiol, Gainesville, FL 32610 USA. [Cook, Robert L.] Univ Florida, Dept Med, Gainesville, FL 32610 USA. [Bass, Michael G.; Bashook, Philip G.; Edison, Marcia] Univ Illinois, Coll Med, Dept Med Educ, Chicago, IL 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. [Cofrancesco, Joseph, Jr.; Berkenblit, Gail V.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Sullivan, Lynn E.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Asch, Steve M.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Sosman, James M.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. RP Cook, RL (reprint author), Univ Florida, Dept Epidemiol, CB 100231, Gainesville, FL 32610 USA. EM cookrl@ufl.edu FU Centers for Disease Control and Prevention; Centers for Disease Control (CDC) [1 U22 PS00551-02]; Robert Wood Johnson Foundation; Health Resources Services Administration for the Midwest AIDS Education and Training Center; National Institutes of Health, National Institute on Drug Abuse [K23 DA019809] FX We want to thank our colleagues at the Society for General Internal Medicine for responding to our survey, and providing thoughtful feedback. We appreciate the funding we received from the Centers for Disease Control and Prevention, and our respective agencies, which allowed us to carry on this work. We wish to especially thank Leslie Dunne, our SGIM project manager, who facilitated this effort to completion.; This work was supported by a grant from the Centers for Disease Control (CDC grant number 1 U22 PS00551-02 HIV Prevention with National Medical Associations), in conjunction with the Society of General Internal Medicine, HIV/AIDS Task Force. Dr. Sullivan was supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program during the conduct of this work. Drs. Bashook and Edison were supported by a grant from the Health Resources Services Administration for the Midwest AIDS Education and Training Center during the conduct of this work. Dr. Korthuis was supported by the National Institutes of Health, National Institute on Drug Abuse (K23 DA019809) during the conduct of this work. NR 36 TC 4 Z9 4 U1 2 U2 5 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 NOV PY 2011 VL 26 IS 11 BP 1258 EP 1264 DI 10.1007/s11606-011-1764-z PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 830UU UT WOS:000295683500009 PM 21710314 ER PT J AU Joo, MJ Au, DH Fitzgibbon, ML McKell, J Lee, TA AF Joo, Min J. Au, David H. Fitzgibbon, Marian L. McKell, Joanne Lee, Todd A. TI Determinants of Spirometry Use and Accuracy of COPD Diagnosis in Primary Care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE chronic disease; diagnosis; health care delivery; chronic obstructive pulmonary disease; spirometry; quality of care ID OBSTRUCTIVE PULMONARY-DISEASE; INHALED CORTICOSTEROID USE; LUNG-FUNCTION; SALMETEROL/FLUTICASONE PROPIONATE; FLUTICASONE PROPIONATE; SALMETEROL; METAANALYSIS; TIOTROPIUM; FORMOTEROL; EFFICACY AB It is unclear if primary care physicians are following guidelines or using other patient characteristics and factors to determine when to perform spirometry in patients at risk for COPD. It is also unclear to what degree a diagnosis of COPD is accurately reflected by spirometry results. To examine characteristics associated with use of spirometry in primary care for patients with increased risk for COPD and to determine the accuracy of COPD diagnosis in patients with spirometry. Retrospective cohort study. A cohort that met the following criteria was identified: a parts per thousand yen35 years of age; a parts per thousand yen 2 primary care visits in internal medicine clinic in 2007; at least one respiratory or smoking cessation medication, or diagnosis of COPD or shortness of breath or dyspnea in 2007. Medical records of all primary care physician visits prior to the time of inclusion in 2007 were reviewed. Data on patient demographics, co-morbidities, respiratory medication use, presence of symptoms, history of tobacco use, and pulmonary function tests were extracted. A total 1052 patients were identified. Dyspnea on exertion (Adjusted odds ratio (AOR) 1.52 [95% CI 1.06-2.18]) and chronic cough (AOR 1.71 [1.07-2.72]) were the only chronic symptoms associated with use of spirometry. Current (AOR 1.54 [0.99-2.40]) or past smoking (AOR 1.09 [0.72-1.65]) status were not associated with use of spirometry. Of the 159 patients with a diagnosis of COPD, 93 (58.5%) met GOLD criteria and 81(50.9%) met lower limit of normal (LLN) criteria for COPD. Clinicians use spirometry more often among patients with symptoms suggestive of COPD but not more often among patients with current or past tobacco use. For patients who had a spirometry and a diagnosis of COPD, primary care physicians were accurate in their diagnosis only half of the time. C1 [Joo, Min J.; Fitzgibbon, Marian L.] Univ Illinois, Dept Med, Sect Hlth Promot Res, Chicago, IL 60612 USA. [Joo, Min J.; McKell, Joanne] Univ Illinois, Dept Med, Sect Pulm Crit Care Sleep & Allergy Med, Chicago, IL 60612 USA. [Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Au, David H.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Lee, Todd A.] Hines VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA. [Lee, Todd A.] Univ Illinois, Dept Pharm Practice, Ctr Pharmacoecon Res, Chicago, IL 60612 USA. RP Joo, MJ (reprint author), Univ Illinois, Dept Med, Sect Hlth Promot Res, 840 S Wood St,M-C 719, Chicago, IL 60612 USA. EM joo@uic.edu FU National Heart, Lung, and Blood Institute [K23HL094461] FX This work was supported by the National Heart, Lung, and Blood Institute [K23HL094461]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NHLBI, the National Institutes. The views expressed in this manuscript reflect those of the authors and not necessarily those of the Department of Veterans Affairs. NR 33 TC 16 Z9 16 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2011 VL 26 IS 11 BP 1272 EP 1277 DI 10.1007/s11606-011-1770-1 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 830UU UT WOS:000295683500011 PM 21713542 ER PT J AU Axon, RN Gebregziabher, M Echols, C Gilbert, G Egede, LE AF Axon, R. Neal Gebregziabher, Mulugeta Echols, Carrae Gilbert, Gregory Egede, Leonard E. TI Racial and Ethnic Differences in Longitudinal Blood Pressure Control in Veterans with Type 2 Diabetes Mellitus SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE blood pressure control; diabetes; epidemiology; race/ethnicity ID CARDIOVASCULAR-DISEASE RISK; SYSTOLIC HYPERTENSION; AFRICAN-AMERICANS; DISPARITIES; CARE; STROKE; RACE; PREVALENCE; MORTALITY; OUTCOMES AB Few studies have examined racial/ethnic differences in blood pressure (BP) control over time, especially in an equal access system. We examined racial/ethnic differences in longitudinal BP control in Veterans with type 2 diabetes. We collected data on a retrospective cohort of 5,319 Veterans with type 2 diabetes and initially uncontrolled BP followed from 1996 to 2006 at a Veterans Administration (VA) facility in the southeastern United States. The mean blood pressure value for each subject for each year was used for the analysis with BP control defined as < 140/< 90 mmHg. The primary outcome measure was proportion with controlled BP. The main predictor variable was race/ethnicity categorized as non-Hispanic White (NHW), non-Hispanic Black (NHB), or Hispanic/Other (H/O). Other covariates included age, gender, employment, marital status, service connectedness, and ICD-9 coded medical and psychiatric comorbidities. Generalized linear mixed models were used to assess the relationship between race/ethnicity and BP control after adjusting for covariates. Mean follow-up was 5.0 years. The sample was 46% NHW, 26% NHB, 19% H/O, and 9% unknown. The average age was 68 years. In the final model, after adjusting for covariates, NHB race (OR = 1.38, 95%CI: 1.2, 1.6) and H/O race (OR = 1.57, 95% CI: 1.3, 1.8) were associated with increased likelihood of poor BP control (> 140/> 90 mmHg) over time compared to NHW patients. Ethnic minority Veterans with type 2 diabetes have significantly increased odds of poor BP control over similar to 5 years of follow-up compared to their non-Hispanic White counterparts independent of sociodemographic factors and comorbidity patterns. C1 [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Axon, R. Neal; Gebregziabher, Mulugeta; Echols, Carrae; Gilbert, Gregory; Egede, Leonard E.] Ralph H Johnson VAMC, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Axon, R. Neal; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu RI Gilbert, Gregory/C-7735-2016 OI Gilbert, Gregory/0000-0003-0879-5496; Gebregziabher, Mulugeta/0000-0002-4826-481X FU Center for Disease Prevention and Health Interventions for Diverse Populations [REA 08-261]; Veterans Affairs Health Services Research and Development FX This study was supported by Grant # REA 08-261, Center for Disease Prevention and Health Interventions for Diverse Populations funded by Veterans Affairs Health Services Research and Development (PI - Leonard Egede). NR 37 TC 10 Z9 10 U1 0 U2 5 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 NOV PY 2011 VL 26 IS 11 BP 1278 EP 1283 DI 10.1007/s11606-011-1752-3 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 830UU UT WOS:000295683500012 PM 21671132 ER PT J AU Lee, CA Chang, A Chou, CL Boscardin, C Hauer, KE AF Lee, Christina A. Chang, Anna Chou, Calvin L. Boscardin, Christy Hauer, Karen E. TI Standardized Patient-Narrated Web-Based Learning Modules Improve Students' Communication Skills on a High-stakes Clinical Skills Examination SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE medical education; clinical skills; standardized patient; communication ID MEDICAL-STUDENTS; HEALTH-PROFESSIONS; PERFORMANCE; SCORES; EDUCATION; CARE; METAANALYSIS; STRATEGIES; MOTIVATION; RESIDENTS AB BACKGROUND: Use of web-based standardized patient (SP) modules is associated with improved medical student history-taking and physical examination skills on clinical performance examinations (CPX), but a benefit for communication skills has not been shown. AIM: We describe an innovative web-based SP module using detailed SP and faculty commentary to teach communication skills. SETTING: A public medical school in 2008-2009. PARTICIPANTS: Fourth-year medical students. PROGRAM DESCRIPTION: A 90-minute web-based module with three simulated clinical encounters was narrated by an expert clinician and SP to explain expected history-taking, physical examination, and communication skills behaviors. All 147 students were encouraged to review the module one month before the CPX. PROGRAME VALUATION: One hundred and six students (72%) viewed the web-based module. Students who watched the module performed significantly higher on the CPX communication score (+2.67%, p < 0.01) and overall score (+2.12%, p = 0.03), even after controlling for USMLE Step 1 and clerkship summary ratings. Use of the module did not significantly affect history/physical examination scores (+1.89%, p = 0.12). DISCUSSION: Students who watched an optional web-based SP module prior to the CPX performed higher than those who did not on communication skills. The web-based module appears to be an effective CPX preparatory activity to enhance communication performance. C1 [Lee, Christina A.] Palo Alto Med Fdn, Palo Alto, CA 94301 USA. [Chang, Anna; Chou, Calvin L.; Boscardin, Christy; Hauer, Karen E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Chang, Anna; Chou, Calvin L.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Lee, CA (reprint author), Palo Alto Med Fdn, 795 El Camino Real, Palo Alto, CA 94301 USA. EM christinaaudreylee@gmail.com OI Boscardin, Christy/0000-0002-9070-8859 FU University of California, San Francisco Academy of Medical Educators FX We thank Bernie Miller and Jewel Smally for assistance with module creation and examination administration and Christian Burke for technical assistance. This study was supported by a University of California, San Francisco Academy of Medical Educators Innovations Grant. NR 34 TC 9 Z9 9 U1 1 U2 4 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 NOV PY 2011 VL 26 IS 11 BP 1374 EP 1377 DI 10.1007/s11606-011-1809-3 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 830UU UT WOS:000295683500027 PM 21769506 ER PT J AU Tantawy, MN Peterson, TE Jones, CK Johnson, K Rook, JM Conn, PJ Baldwin, RM Ansari, MS Kessler, RM AF Tantawy, Mohammed N. Peterson, Todd E. Jones, Carrie K. Johnson, Kari Rook, Jerri M. Conn, P. Jeffrey Baldwin, Ronald M. Ansari, M. Sib Kessler, Robert M. TI Impact of Isoflurane Anesthesia on D2 Receptor Occupancy by [F-18]fallypride Measured by MicroPET With a Modified Logan Plot SO SYNAPSE LA English DT Article DE [F-18]fallypride; dopamine (DA) receptors; isoflurane; graphical analysis; microPET ID POSITRON-EMISSION-TOMOGRAPHY; DOPAMINE RELEASE; RAT-BRAIN; NONHUMAN-PRIMATES; IN-VIVO; BINDING; PET; RADIOLIGAND; STRIATUM; REGIONS AB In the previous work, we reported a method that utilized imaging data collected from 60 to 120 min following [F-18] fallypride administration to estimate the distribution volume ratio DVR' (DVR' proportional to DVR; DVR = 1 + BPND, where BPND is a measure of receptor density, DA D2 in this case). In this work, we use this method to assess the effects of isoflurane anesthesia on [F-18] fallypride DVR'. Methods: Rats were injected with [F-18] fallypride either unconsciously under similar to 1.5% isoflurane via the tail vein (Group 1) or consciously via a catheter inserted either in the jugular vein (Group 2) or the tail vein (Group 3). After about 1 h of free access to food and water the rats were anesthetized with 1.5% isoflurane and imaged in a microPET for 60 min. The rats that were injected consciously (Groups 2 and 3) were placed in a rat restrainer during [F-18]fallypride injection. They were habituated in that restrainer for 3 days prior to the experiment day to minimize restraint-related stress. For comparison, a control group of rats was imaged for 120 min simultaneously with the administration of [F-18]fallypride i.v. while under 1.5% isoflurane. The DVR' estimates from the 60 min acquisitions were compared with the DVR' from the last 60 min of the 120 min acquisitions (after neglecting the first 60 min). In addition, the striatal time-activity curves were fit with a 2-tissue + plasma compartment model using an arbitrary simulated plasma input function to obtain k(3)/k(4) (approximate to BPND) for the 60 and 120 min acquisitions. Results: Isoflurane anesthesia caused a significant reduction, up to 22%, in the DVR' estimates, which were 15.7 +/- 0.3 (mean +/- SE) for the controls, 17.7 +/- 0.3 for Group 1, 19.2 +/- 0.4 for Group 2, and 18.8 +/- 0.7 for Group 3. The compartmental model fit produced similar results, similar to 30% reduction in k(3)/k(4) for the 120-min acquisitions compared with the 60-min acquisitions (initial conscious uptake of the radiotracer). Conclusion: The results of this study demonstrate that isoflurane anesthesia significantly decreases striatal [F-18] fallypride BPND in rats. Of similar importance, this work demonstrates the effectiveness of delayed scans following radiotracer injection and the implication that different types of studies can be conducted simultaneously with this method, including studies of behavioral and environmental impact on brain receptors. Synapse 65:1173-1180, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Tantawy, Mohammed N.; Peterson, Todd E.; Baldwin, Ronald M.; Ansari, M. Sib; Kessler, Robert M.] Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA. [Tantawy, Mohammed N.; Peterson, Todd E.; Baldwin, Ronald M.] Vanderbilt Univ, Med Ctr, Inst Imaging Sci, Nashville, TN 37232 USA. [Jones, Carrie K.; Johnson, Kari; Rook, Jerri M.; Conn, P. Jeffrey] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Jones, Carrie K.; Johnson, Kari; Rook, Jerri M.; Conn, P. Jeffrey] Vanderbilt Univ, Med Ctr, Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA. [Jones, Carrie K.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. EM n.tantawy@vanderbilt.edu RI Conn, Peter/D-7848-2012 FU NCRR [1S10 RR17858]; Burroughs Welcome Fund FX Contract grant sponsor: NCRR; Contract grant number: 1S10 RR17858; The authors thank Jarrod True, Zou Yue, and Silvia Cambronero for their assistance with the animal handling and injections. The research of Todd E. Peterson, Ph.D. is supported by a Career Award at the Scientific Interface from the Burroughs Welcome Fund. NR 35 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0887-4476 J9 SYNAPSE JI Synapse PD NOV PY 2011 VL 65 IS 11 BP 1173 EP 1180 DI 10.1002/syn.20955 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 827UU UT WOS:000295455100007 PM 21584868 ER PT J AU Doyle, SR Donovan, DM Simpson, TL AF Doyle, Suzanne R. Donovan, Dennis M. Simpson, Tracy L. TI Validation of a nine-dimensional measure of drinking motives for use in clinical applications: The desired effects of drinking scale SO ADDICTIVE BEHAVIORS LA English DT Article DE Drinking motives; Confirmatory factor analysis; Concurrent validity; Predictive validity ID ALCOHOL-RELATED PROBLEMS; COLLEGE-STUDENTS; YOUNG-PEOPLE; REASONS; EXPECTANCIES; SAMPLE; QUESTIONNAIRE; DRINKERS; BEHAVIOR; INSTRUMENT AB The Desired Effects of Drinking (DEOD) is a 36-item, 9-subscale, self-report measure assessing reasons for drinking, concerning three general motives for alcohol use: Coping, Social, and Enhancement. These subscales include Negative Feelings, Self-esteem, Relief, Positive Feelings, Social Facilitation, Assertion, Drug Effects, Sexual Enhancement, and Mental effects. As part of the COMBINE study, scores from the nine DEOD subscales, along with additional information about alcohol consumption and consequences, were incorporated into personalized client feedback as part of a motivational enhancement intervention and as a guide for the development of a plan for treatment and change. With responses from a clinical sample of 572 individuals seeking alcohol treatment, the 9-subscale structure of the instrument was substantiated through a second-order confirmatory factor analysis, revealing moderately large to large factor loadings and good indices of model fit. A third-order factor analysis indicated these nine subscales adequately represented the three drinking motives. It is suggested these three general motives for alcohol use, which may be more distinctly delineated into the nine dimensions reflected in the DEOD structure, can be used clinically to help plan appropriate interventions and facilitate behavior change. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Doyle, Suzanne R.; Donovan, Dennis M.] Univ Washington, Alcohol & Drug Abuse Inst, Seattle, WA 98105 USA. [Donovan, Dennis M.; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Doyle, SR (reprint author), Univ Washington, Alcohol & Drug Abuse Inst, 1107 NE 45th St,Suite 120, Seattle, WA 98105 USA. EM srdoyle@u.washington.edu FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [U10AA11715, 11716, 11721, 11727, 11756, 11768, 11773, 11776, 11777, 11783, 11787, 11799]; Combine Study Research Group; [U10AA011799] FX The authors gratefully acknowledge support of the COMBINE study by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) through Cooperative Agreements U10AA11715, 11716, 11721, 11727, 11756, 11768, 11773, 11776, 11777, 11783, 11787, 11799, and 11773.; Data presented in this report were collected as part of the multisite COMBINE trial Sponsored by the National Institute on Alcohol Abuse and Alcoholism, in collaboration with the Combine Study Research Group. Preparation of this report was supported in part by grant U10AA011799. A full listing of the staff of the COMBINE study can be found at http://www.cscc.unc.edu/combine/. NR 64 TC 13 Z9 13 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD NOV PY 2011 VL 36 IS 11 BP 1052 EP 1060 DI 10.1016/j.addbeh.2011.06.012 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 821OM UT WOS:000294984300005 PM 21782346 ER PT J AU Furuno, JP Johnson, JK Schweizer, ML Uche, A Stine, OC Shurland, SM Forrest, GN AF Furuno, Jon P. Johnson, Jennifer K. Schweizer, Marin L. Uche, Anayochukwu Stine, Oscar C. Shurland, Simone M. Forrest, Graeme N. TI Community-associated Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis among HIV Patients: A cohort study SO BMC INFECTIOUS DISEASES LA English DT Article ID INJECTION-DRUG USERS; INFECTIVE ENDOCARDITIS; RISK-FACTORS; ANTIRETROVIRAL THERAPY; ANTIBIOTIC-THERAPY; MRSA BACTEREMIA; UNITED-STATES; MORTALITY; USA300; STRAINS AB Background: HIV patients are at increased risk of development of infections and infection-associated poor health outcomes. We aimed to 1) assess the prevalence of USA300 community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) among HIV-infected patients with S. aureus bloodstream infections and. 2) determine risk factors for infective endocarditis and in-hospital mortality among patients in this population. Methods: All adult HIV-infected patients with documented S. aureus bacteremia admitted to the University of Maryland Medical Center between January 1, 2003 and December 31, 2005 were included. CA-MRSA was defined as a USA300 MRSA isolate with the MBQBLO spa-type motif and positive for both the arginine catabolic mobile element and Panton-Valentin Leukocidin. Risk factors for S. aureus-associated infective endocarditis and mortality were determined using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Potential risk factors included demographic variables, comorbid illnesses, and intravenous drug use. Results: Among 131 episodes of S. aureus bacteremia, 85 (66%) were MRSA of which 47 (54%) were CA-MRSA. Sixty-three patients (48%) developed endocarditis and 10 patients (8%) died in the hospital on the index admission Patients with CA-MRSA were significantly more likely to develop endocarditis (OR = 2.73, 95% CI = 1.30, 5.71). No other variables including comorbid conditions, current receipt of antiretroviral therapy, pre-culture severity of illness, or CD4 count were significantly associated with endocarditis and none were associated with in-hospital mortality. Conclusions: CA-MRSA was significantly associated with an increased incidence of endocarditis in this cohort of HIV patients with MRSA bacteremia. In populations such as these, in which the prevalence of intravenous drug use and probability of endocarditis are both high, efforts must be made for early detection, which may improve treatment outcomes. C1 [Forrest, Graeme N.] Portland VA Med Ctr, Div Infect Dis, Portland, OR USA. [Forrest, Graeme N.] Oregon Hlth & Sci Univ, Portland, OR USA. [Furuno, Jon P.] Oregon State Univ, Oregon Hlth & Sci Coll Pharm, Dept Pharm Practice, Portland, OR USA. [Johnson, Jennifer K.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Schweizer, Marin L.] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. [Furuno, Jon P.; Stine, Oscar C.; Shurland, Simone M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Uche, Anayochukwu] Oro Valley Hosp, Oro Valley, AZ USA. [Shurland, Simone M.] US FDA, Silver Spring, MD USA. RP Forrest, GN (reprint author), Portland VA Med Ctr, Div Infect Dis, Portland, OR USA. EM forrestg@ohsu.edu FU National Institutes of Health [M01 RR16500]; University of Maryland General Clinical Research Center [1K01AI071015-03, 1K12RR023250-04]; Southern Medical Association; Cubist Pharmaceuticals, Inc.; Pfizer Inc. FX National Institutes of Health Grants M01 RR16500, University of Maryland General Clinical Research Center, 1K01AI071015-03 (J.P.F.) and 1K12RR023250-04 (J.K.J.) and a grant from the Southern Medical Association (A.U.).; In the past 5 years J.P.F. and M.L.S. have served as consults for Cubist Pharmaceuticals, Inc. Also, G.N.F. has received research funding and honoraria from Cubist Pharmaceuticals, Inc. and Pfizer Inc. M.L.S. has received research funding from Pfizer, Inc. NR 43 TC 21 Z9 22 U1 1 U2 1 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 OCT 31 PY 2011 VL 11 AR 298 DI 10.1186/1471-2334-11-298 PG 7 WC Infectious Diseases SC Infectious Diseases GA 846MX UT WOS:000296909000001 PM 22040268 ER PT J AU Ellis, LZ Liu, WM Luo, YC Okamoto, M Qu, D Dunn, JH Fujita, M AF Ellis, Lixia Z. Liu, Weimin Luo, Yuchun Okamoto, Miyako Qu, Dovina Dunn, Jeffrey H. Fujita, Mayumi TI Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1 beta secretion SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Green tea; Epigallocatechin-3-gallate; Melanoma; IL-1; Inflammasome; NLRP1 ID NF-KAPPA-B; CELLS; (-)-EPIGALLOCATECHIN-3-GALLATE; ACTIVATION; MICE; CANCER; PHARMACOKINETICS; METABOLITES; APOPTOSIS; CATECHINS AB Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, has been demonstrated to possess anti-inflammatory, antioxidant, anti-mutagenic and anti-carcinogenic properties. The anti-melanoma effect of EGCG has been previously suggested, but no clear mechanism of action has been established. In this study, we demonstrated that EGCG inhibits melanoma cell growth at physiological doses (0.1-1 mu M). In the search for mechanisms of EGCG-mediated melanoma cell suppression, we found that NF-kappa B was inhibited, and that reduced NF-kappa B activity was associated with decreased IL-1 beta secretion from melanoma cells. Since inflammasomes are involved in IL-1 beta secretion, we investigated whether IL-1 beta suppression was mediated by inflammasomes, and found that EGCG treatment led to downregulation of the inflammasome component, NLRP1, and reduced caspase-1 activation. Furthermore, silencing the expression of NLRP1 abolished EGCG-induced inhibition of tumor cell proliferation both in vitro and in vivo, suggesting a key role of inflammasomes in EGCG efficacy. This paper provides a novel mechanism for EGCG-induced melanoma inhibition: inflammasome downregulation -> decreased IL-1 beta secretion -> decreased NF-kappa B activities -> decreased cell growth. In addition, it suggests inflammasomes and IL-1 beta could be potential targets for future melanoma therapeutics. Published by Elsevier Inc. C1 [Ellis, Lixia Z.; Liu, Weimin; Luo, Yuchun; Okamoto, Miyako; Qu, Dovina; Dunn, Jeffrey H.; Fujita, Mayumi] Univ Colorado, Sch Med, Dept Dermatol, Aurora, CO 80045 USA. [Fujita, Mayumi] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Fujita, M (reprint author), Univ Colorado, Sch Med, Dept Dermatol, Mail Stop 8127,12801 E 17th Ave,Room 4124, Aurora, CO 80045 USA. EM mayumi.fujita@ucdenver.edu RI Luo, Yuchun/B-8683-2014 FU Dermatology Foundation; Tadamitsu Cancer Research Fund; NIH [CA125833, 5T32AR007411]; Wendy Will Cancer Center FX This work was supported by Grants from the Dermatology Foundation (to M.F.), the Tadamitsu Cancer Research Fund (to M.F.), NIH Grants CA125833 (to M.F.), and the Wendy Will Cancer Center Fund (to M.F.). W.L. and M.O. were supported by a training grant from NIH (5T32AR007411). NR 32 TC 42 Z9 46 U1 9 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 28 PY 2011 VL 414 IS 3 BP 551 EP 556 DI 10.1016/j.bbrc.2011.09.115 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 868JL UT WOS:000298519500019 PM 21982776 ER PT J AU Chaney, EF Rubenstein, LV Liu, CF Yano, EM Bolkan, C Lee, M Simon, B Lanto, A Felker, B Uman, J AF Chaney, Edmund F. Rubenstein, Lisa V. Liu, Chuan-Fen Yano, Elizabeth M. Bolkan, Cory Lee, Martin Simon, Barbara Lanto, Andy Felker, Bradford Uman, Jane TI Implementing collaborative care for depression treatment in primary care: A cluster randomized evaluation of a quality improvement practice redesign SO IMPLEMENTATION SCIENCE LA English DT Article ID MENTAL-HEALTH; QUERI SERIES; VETERANS; OUTCOMES; INTERVENTIONS; MANAGEMENT; PROGRAMS; IMPACT; ORGANIZATIONS; GUIDELINES AB Background: Meta-analyses show collaborative care models (CCMs) with nurse care management are effective for improving primary care for depression. This study aimed to develop CCM approaches that could be sustained and spread within Veterans Affairs (VA). Evidence-based quality improvement (EBQI) uses QI approaches within a research/clinical partnership to redesign care. The study used EBQI methods for CCM redesign, tested the effectiveness of the locally adapted model as implemented, and assessed the contextual factors shaping intervention effectiveness. Methods: The study intervention is EBQI as applied to CCM implementation. The study uses a cluster randomized design as a formative evaluation tool to test and improve the effectiveness of the redesign process, with seven intervention and three non-intervention VA primary care practices in five different states. The primary study outcome is patient antidepressant use. The context evaluation is descriptive and uses subgroup analysis. The primary context evaluation measure is naturalistic primary care clinician (PCC) predilection to adopt CCM. For the randomized evaluation, trained telephone research interviewers enrolled consecutive primary care patients with major depression in the evaluation, referred enrolled patients in intervention practices to the implemented CCM, and re-surveyed at seven months. Results: Interviewers enrolled 288 CCM site and 258 non-CCM site patients. Enrolled intervention site patients were more likely to receive appropriate antidepressant care (66% versus 43%, p = 0.01), but showed no significant difference in symptom improvement compared to usual care. In terms of context, only 40% of enrolled patients received complete care management per protocol. PCC predilection to adopt CCM had substantial effects on patient participation, with patients belonging to early adopter clinicians completing adequate care manager follow-up significantly more often than patients of clinicians with low predilection to adopt CCM (74% versus 48%%, p = 0.003). Conclusions: Depression CCM designed and implemented by primary care practices using EBQI improved antidepressant initiation. Combining QI methods with a randomized evaluation proved challenging, but enabled new insights into the process of translating research-based CCM into practice. Future research on the effects of PCC attitudes and skills on CCM results, as well as on enhancing the link between improved antidepressant use and symptom outcomes, is needed. C1 [Chaney, Edmund F.; Liu, Chuan-Fen; Felker, Bradford] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Rubenstein, Lisa V.; Yano, Elizabeth M.; Lee, Martin; Simon, Barbara; Lanto, Andy] VA Greater Los Angeles Healthcare Syst, VA Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. [Rubenstein, Lisa V.] RAND Hlth Program, Santa Monica, CA USA. [Rubenstein, Lisa V.; Yano, Elizabeth M.; Lee, Martin] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rubenstein, Lisa V.; Yano, Elizabeth M.; Lee, Martin] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Liu, Chuan-Fen; Uman, Jane] VA Puget Sound Hlth Care Syst, HSR&D NW Ctr Excellence Outcomes Res Older Adults, Seattle, WA USA. [Bolkan, Cory] Washington State Univ, Dept Human Dev, Vancouver, WA USA. RP Chaney, EF (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. EM chaney@u.washington.edu FU Department of Veterans Affairs (VA) Health Services Research and Development (HSRD) Service [MHI-99-375]; VA HSR&D Research Career Scientist award [RCS 09-095] FX Funding was provided by Department of Veterans Affairs (VA) Health Services Research and Development (HSR&D) Service (grant number MHI-99-375). The VA HSR&D Mental Health Quality Enhancement Research Initiative (QUERI) staff provided critical assistance and oversight. Dr. Yano's salary support during a portion of this work was provided by a VA HSR&D Research Career Scientist award (grant number RCS 09-095). We would like to specifically acknowledge the contributions of Laura Bonner, Duncan Campbell, Jonathan Kanter, Debbie Mittman, Carol Oken, Carol Simons, Susan Vivell and all other WAVES project research staff. The study would not have been possible without the active partnership and leadership of Randy Petzel, Scott Ober, Kathy Henderson, Joanne Kirchner, Mike Davies, and all other participating administrators and clinicians of VA VISNs 10, 16, and 23. Finally we thank VA Nursing Service and more specifically Karen Vollen and Barbara Revay, pioneering TIDES DCMs and the first TIDES nurse trainers. There are no contractual rights to review the manuscript before submission, but there is a requirement that Health Services Research and Development, Department of Veterans Affairs, be given a copy of the accepted manuscript NR 61 TC 27 Z9 29 U1 0 U2 7 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 OCT 27 PY 2011 VL 6 AR 121 DI 10.1186/1748-5908-6-121 PG 15 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 849LX UT WOS:000297128100001 PM 22032247 ER PT J AU McGregor, R Wu, MF Barber, G Ramanathan, L Siegel, JM AF McGregor, Ronald Wu, Ming-Fung Barber, Grace Ramanathan, Lalini Siegel, Jerome M. TI Highly Specific Role of Hypocretin (Orexin) Neurons: Differential Activation as a Function of Diurnal Phase, Operant Reinforcement versus Operant Avoidance and Light Level SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PARKINSONS-DISEASE; SLEEP-DEPRIVATION; HUMAN NARCOLEPSY; FOS EXPRESSION; KNOCKOUT MICE; MUSCLE TONE; RATS; CATAPLEXY; AROUSAL; LESIONS AB Hypocretin (Hcrt) cell loss is responsible for narcolepsy, but Hcrt's role in normal behavior is unclear. We found that Hcrt knock-out mice were unable to work for food or water reward during the light phase. However, they were unimpaired relative to wild-type (WT) mice when working for reward during the dark phase or when working to avoid shock in the light or dark phase. In WT mice, expression of Fos in Hcrt neurons occurs only in the light phase when working for positive reinforcement. Expression was seen throughout the mediolateral extent of the Hcrt field. Fos was not expressed when expected or unexpected unearned rewards were presented, when working to avoid negative reinforcement, or when given or expecting shock, even though these conditions elicit maximal electroencephalogram (EEG) arousal. Fos was not expressed in the light phase when light was removed. This may explain the lack of light-induced arousal in narcoleptics and its presence in normal individuals. This is the first demonstration of such specificity of arousal system function and has implications for understanding the motivational and circadian consequences of arousal system dysfunction. The current results also indicate that comparable and complementary specificities must exist in other arousal systems. C1 [McGregor, Ronald; Wu, Ming-Fung; Barber, Grace; Ramanathan, Lalini; Siegel, Jerome M.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [McGregor, Ronald; Wu, Ming-Fung; Barber, Grace; Ramanathan, Lalini; Siegel, Jerome M.] Vet Adm Greater Los Angeles Healthcare Syst, North Hills, CA 91343 USA. [McGregor, Ronald; Wu, Ming-Fung; Barber, Grace; Ramanathan, Lalini; Siegel, Jerome M.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. EM JSiegel@ucla.edu FU National Institutes of Health [NS14610, MH64109, NS069640]; Medical Research Service of the Department of Veteran Affairs FX This work was supported by Grants NS14610, MH64109, and NS069640 from the National Institutes of Health and the Medical Research Service of the Department of Veteran Affairs. We thank Masashi Yanagisawa for providing us with the orexin KO mice, and Lisa Boehmer and Krystal Abordo for genotyping the mice. A preliminary report of some of these data was previously presented in abstract form (McGregor et al., 2007). NR 62 TC 33 Z9 33 U1 2 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 26 PY 2011 VL 31 IS 43 BP 15455 EP 15467 DI 10.1523/JNEUROSCI.4017-11.2011 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 840MZ UT WOS:000296446200025 PM 22031892 ER PT J AU Covinsky, KE Pierluissi, E Johnston, CB AF Covinsky, Kenneth E. Pierluissi, Edgar Johnston, C. Bree TI Hospitalization-Associated Disability "She Was Probably Able to Ambulate, but I'm Not Sure" SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PREDICTS FUNCTIONAL DECLINE; ACUTE MEDICAL ILLNESS; ILL OLDER PATIENTS; LONG-TERM-CARE; RANDOMIZED-TRIAL; LOW MOBILITY; MULTICOMPONENT INTERVENTION; GERIATRIC ASSESSMENT; RESTRICTED ACTIVITY; ELDERLY PATIENTS AB In older patients, acute medical illness that requires hospitalization is a sentinel event that often precipitates disability. This results in the subsequent inability to live independently and complete basic activities of daily living (ADLs). This hospitalization-associated disability occurs in approximately one-third of patients older than 70 years of age and may be triggered even when the illness that necessitated the hospitalization is successfully treated. In this article, we describe risk factors and risk stratification tools that identify older adults at highest risk of hospitalization-associated disability. We describe hospital processes that may promote hospitalization-associated disability and models of care that have been developed to prevent it. Since recognition of functional status problems is an essential prerequisite to preventing and managing disability, we also describe a pragmatic approach toward functional status assessment in the hospital focused on evaluation of ADLs, mobility, and cognition. Based on studies of acute geriatric units, we describe interventions hospitals and clinicians can consider to prevent hospitalization-associated disability in patients. Finally, we describe approaches clinicians can implement to improve the quality of life of older adults who develop hospitalization-associated disability and that of their caregivers. JAMA. 2011;306(16):1782-1793 C1 [Covinsky, Kenneth E.; Pierluissi, Edgar; Johnston, C. Bree] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. [Covinsky, Kenneth E.; Pierluissi, Edgar; Johnston, C. Bree] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Pierluissi, Edgar] San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA. [Pierluissi, Edgar] San Francisco Gen Hosp, Div Hosp Med, San Francisco, CA 94110 USA. [Covinsky, Kenneth E.; Johnston, C. Bree] San Francisco VA Med Ctr, Sect Geriatr & Palliat Care, San Francisco, CA USA. RP Covinsky, KE (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement St 181G, San Francisco, CA 94121 USA. EM ken.covinsky@ucsf.edu FU National Institute on Aging; SCAN Foundation FX This work was supported in part by a K24 midcareer investigator award from the National Institute on Aging (Covinsky). The Care of the Aging Patient series is made possible by funding from The SCAN Foundation. NR 72 TC 151 Z9 153 U1 4 U2 25 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 OCT 26 PY 2011 VL 306 IS 16 BP 1782 EP 1793 DI 10.1001/jama.2011.1556 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 837HH UT WOS:000296181600023 PM 22028354 ER PT J AU Kangovi, S Grande, D AF Kangovi, Shreya Grande, David TI Hospital Readmissions-Not Just a Measure of Quality SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID INSURANCE STATUS; FOLLOW-UP; CARE; ACCESS; IMPACT C1 [Kangovi, Shreya] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Grande, David] Univ Penn, Perelman Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Kangovi, Shreya; Grande, David] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Kangovi, Shreya] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Kangovi, S (reprint author), Univ Penn, Robert Wood Johnson Clin Scholars Program, 423 Guardian Dr,13th Floor,Blockley Hall, Philadelphia, PA 19104 USA. EM kangovi@mail.med.upenn.edu NR 10 TC 62 Z9 62 U1 0 U2 6 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 OCT 26 PY 2011 VL 306 IS 16 BP 1796 EP 1797 DI 10.1001/jama.2011.1562 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 837HH UT WOS:000296181600025 PM 22028356 ER PT J AU Piller, LB Baraniuk, S Simpson, LM Cushman, WC Massie, BM Einhorn, PT Oparil, S Ford, CE Graumlich, JF Dart, RA Parish, DC Retta, TM Cuyjet, AB Jafri, SZ Furberg, CD Saklayen, MG Thadani, U Probstfield, JL Davis, BR AF Piller, Linda B. Baraniuk, Sarah Simpson, Lara M. Cushman, William C. Massie, Barry M. Einhorn, Paula T. Oparil, Suzanne Ford, Charles E. Graumlich, James F. Dart, Richard A. Parish, David C. Retta, Tamrat M. Cuyjet, Aloysius B. Jafri, Syed Z. Furberg, Curt D. Saklayen, Mohammad G. Thadani, Udho Probstfield, Jeffrey L. Davis, Barry R. CA ALLHAT Collaborative Res Grp TI Long-Term Follow-Up of Participants With Heart Failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) SO CIRCULATION LA English DT Article DE heart failure; hypertension; diuretics; mortality; ejection fraction ID CONVERTING-ENZYME-INHIBITOR; CARDIOVASCULAR EVENTS; SURVIVAL; HYPERTENSION; RISK; BLOCKER; TRENDS; OLDER AB Background-In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in high-risk hypertensive participants, risk of new-onset heart failure (HF) was higher in the amlodipine (2.5-10 mg/d) and lisinopril (10-40 mg/d) arms compared with the chlorthalidone (12.5-25 mg/d) arm. Similar to other studies, mortality rates following new-onset HF were very high (>= 50% at 5 years), and were similar across randomized treatment arms. After the randomized phase of the trial ended in 2002, outcomes were determined from administrative databases. Methods and Results-With the use of national databases, posttrial follow-up mortality through 2006 was obtained on participants who developed new-onset HF during the randomized (in-trial) phase of ALLHAT. Mean follow-up for the entire period was 8.9 years. Of 1761 participants with incident HF in-trial, 1348 died. Post-HF all-cause mortality was similar across treatment groups, with adjusted hazard ratios (95% confidence intervals) of 0.95 (0.81-1.12) and 1.05 (0.89-1.25), respectively, for amlodipine and lisinopril compared with chlorthalidone, and 10-year adjusted rates of 86%, 87%, and 83%, respectively. All-cause mortality rates were also similar among those with reduced ejection fractions (84%) and preserved ejection fractions (81%), with no significant differences by randomized treatment arm. Conclusions-Once HF develops, risk of death is high and consistent across randomized treatment groups. Measures to prevent the development of HF, especially blood pressure control, must be a priority if mortality associated with the development of HF is to be addressed. C1 [Piller, Linda B.; Baraniuk, Sarah; Simpson, Lara M.; Ford, Charles E.; Davis, Barry R.] Univ Texas Sch Publ Hlth, Houston, TX 77030 USA. [Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Einhorn, Paula T.] NHLBI, Bethesda, MD 20892 USA. [Oparil, Suzanne] Univ Alabama Birmingham, Birmingham, AL USA. [Graumlich, James F.] Univ Illinois, Coll Med, Peoria, IL 61656 USA. [Dart, Richard A.] Marshfield Clin Res Fdn, Marshfield, WI USA. [Parish, David C.] Mercer Univ, Sch Med, Macon, GA 31207 USA. [Retta, Tamrat M.] Howard Univ, Coll Med, Washington, DC USA. [Cuyjet, Aloysius B.] Nassau Univ, Med Ctr, E Meadow, NY USA. [Jafri, Syed Z.] Fargo Vet Affairs Med Ctr, Fargo, ND USA. [Furberg, Curt D.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Saklayen, Mohammad G.] Vet Affairs Med Ctr, Dayton, OH USA. [Saklayen, Mohammad G.] Wright State Univ, Dayton, OH 45435 USA. [Thadani, Udho] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Thadani, Udho] Dept Vet Affairs Med Ctr, Oklahoma City, OK USA. [Probstfield, Jeffrey L.] Univ Washington, Seattle, WA 98195 USA. RP Piller, LB (reprint author), Univ Texas Sch Publ Hlth, 1200 Pressler St,W-906, Houston, TX 77030 USA. EM Linda.B.Piller@uth.tmc.edu FU National Heart, Lung, and Blood Institute [NO1-HC-35130]; Pfizer, Inc.; GlaxoSmithKline; Merck; Novartis; Corthera; Takeda; Amgen; Daiichi Sankyo; Gilead; Omron Healthcare; Pfizer; Schering Plough; Abbot Laboratories; Boehringer Ingelheim; Sanofi-aventis; Bristol-Myers Squibb; Eisai Medical Research; Eli Lilly; NIH; Schering-Plough FX This study was supported by contract NO1-HC-35130 with the National Heart, Lung, and Blood Institute. The ALLHAT investigators acknowledge study medications contributed by Pfizer, Inc. (amlodipine and doxazosin), AstraZeneca (atenolol and lisinopril), and Bristol-Myers Squibb (pravastatin), and financial support provided by Pfizer, Inc.; Dr Cushman has consulted for Daiichi Sankyo, Novartis, Noven, Sanofi-aventis, Takeda, and Theravance; has received honoraria from Bristol-Myers Squibb, and has received research grants from GlaxoSmithKline, Merck, and Novartis. Dr Davis has consulted for Amgen and Takeda. Dr. Massie has consulted for Averion, Bristol-Myers Squibb, Gilead, Merck, Nile Therapeutics, Novartis, and Sanofi-aventis, and has received payments for serving on the DSMB from Corthera and Takeda. Dr Oparil has consulted for Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Forest Pharmaceuticals, NicOx, and Novartis, and has received research grants from Amgen, Daiichi Sankyo, Gilead, Omron Healthcare, Pfizer, Schering Plough, and Takeda. Dr Probstfield has received research grants from Abbot Laboratories, Boehringer Ingelheim, GlaxoSmithKline, and Sanofi-aventis. Dr Thadani has consulted for Forest Laboratories, Gilead Colorado, Lilly/ICOS, and Merck; has received honoraria from Daiichi Sankyo and Eli Lilly; and has received research grants from Bristol-Myers Squibb, Eisai Medical Research, Eli Lilly, NIH, Novartis, Pfizer, and Schering-Plough. The other authors report no conflicts. NR 29 TC 17 Z9 19 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD OCT 25 PY 2011 VL 124 IS 17 BP 1811 EP U88 DI 10.1161/CIRCULATIONAHA.110.012575 PG 14 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 842EY UT WOS:000296576500012 PM 21969009 ER PT J AU Tsai, TT Messenger, JC Brennan, M Patel, UD Dai, D Piana, RN Anstrom, KJ Eisenstein, EL Dokholyan, RS Peterson, ED Douglas, PS AF Tsai, Thomas T. Messenger, John C. Brennan, Matthew Patel, Uptal D. Dai, David Piana, Robert N. Anstrom, Kevin J. Eisenstein, Eric L. Dokholyan, Rachel S. Peterson, Eric D. Douglas, Pamela S. TI Safety and Efficacy of Drug-Eluting Stents in Older Patients With Chronic Kidney Disease A Report From the Linked CathPCI Registry-CMS Claims Database SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE comparative effectiveness research; drug-eluting stent(s); renal insufficiency ID CHRONIC RENAL-INSUFFICIENCY; BARE-METAL STENTS; PERCUTANEOUS CORONARY REVASCULARIZATION; CARDIOVASCULAR DATA REGISTRY; LONG-TERM OUTCOMES; TAXUS-IV TRIAL; OFF-LABEL USE; AMERICAN-COLLEGE; MYOCARDIAL-INFARCTION; CLINICAL-OUTCOMES AB Objectives The purpose of this study was to determine the safety and efficacy of drug-eluting stents (DES) compared with bare-metal stents (BMS) in older patients with chronic kidney disease (CKD). Background DES may be associated with late death and myocardial infarction (MI) secondary to stent thrombosis. However, data on outcomes in older patients with CKD are limited. Methods We estimated the glomerular filtration rate (GFR) of 283,593 patients 65 years of age and older who underwent stent implantation between 2004 and 2007. In propensity-matched cohorts grouped by GFR, the association between DES and BMS and the risk of death, MI, revascularization, and major bleeding was examined. Results A total of 121,446 patients (42.8%) had CKD (GFR <60 ml/min/1.73 m(2)). The 30-month mortality rate for patients on long-term dialysis was 52.0%. In propensity-matched pairs, placement of a DES compared with a BMS in patients with normal renal function was associated with significant reductions in 30-month revascularization (hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.86 to 0.95), MI (HR: 0.77; 95% CI: 0.71 to 0.83), and death (HR: 0.73; 95% CI: 0.69 to 0.77), but no difference in bleeding (HR: 0.89; 95% CI: 0.79 to 1.00). Lower MI and mortality rates were also observed after DES compared with BMS implantation in all CKD subgroups with the exception of MI in the long-term dialysis group. Decreased rates of revascularization did not extend to any subgroup of patients with CKD. Conclusions The safety of DES compared with BMS is observed in all patients regardless of renal function and is associated with reduced rates of MI and death in some subsets of patients with CKD. (J Am Coll Cardiol 2011; 58: 1859-69) (C) 2011 by the American College of Cardiology Foundation C1 [Tsai, Thomas T.] Denver VA Med Ctr, Cardiol Sect 111B, Denver, CO 80220 USA. [Tsai, Thomas T.; Messenger, John C.] Univ Colorado, Aurora, CO USA. [Brennan, Matthew; Patel, Uptal D.; Dai, David; Anstrom, Kevin J.; Eisenstein, Eric L.; Dokholyan, Rachel S.; Peterson, Eric D.; Douglas, Pamela S.] Duke Univ Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Piana, Robert N.] Vanderbilt Univ Sch Med, Nashville, TN USA. RP Tsai, TT (reprint author), Denver VA Med Ctr, Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80220 USA. EM Thomas.Tsai@va.gov FU Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) [HHSA29020050032I]; Medtronic Cardiovascular; Eli Lilly Co.; Bristol-Myers Squibb/Sanofi; Merck; Lilly; Johnson Johnson FX This project was funded under contract no. HHSA29020050032I Task Order No. 4 from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program. The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services. Dr. Eisenstein has received grant support from Medtronic Cardiovascular and Eli Lilly & Co. Dr. Peterson has received research support from Bristol-Myers Squibb/Sanofi, Merck, Lilly, and Johnson & Johnson. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 43 TC 44 Z9 45 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 OCT 25 PY 2011 VL 58 IS 18 BP 1859 EP 1869 DI 10.1016/j.jacc.2011.06.056 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 841UM UT WOS:000296540200005 PM 22018296 ER PT J AU Deswal, A AF Deswal, Anita TI Obesity, Leptin, and Incident Heart Failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE heart failure; leptin; obesity ID RAT VENTRICULAR MYOCYTES; ATHEROSCLEROSIS; RISK; MICE; HYPERTROPHY; APOPTOSIS; DISEASE C1 [Deswal, Anita] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Cardiol Sect, Houston, TX 77030 USA. [Deswal, Anita] Baylor Coll Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. RP Deswal, A (reprint author), Michael E DeBakey VA Med Ctr 111B, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM adeswal@bcm.edu NR 19 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 25 PY 2011 VL 58 IS 18 BP 1878 EP 1880 DI 10.1016/j.jacc.2011.07.030 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 841UM UT WOS:000296540200007 PM 22018298 ER PT J AU Pau, VPT Smith, FJ Taylor, AB Parfenova, LV Samakai, E Callaghan, MM Abarca-Heidemann, K Hart, PJ Rothberg, BS AF Pau, Victor P. T. Smith, Frank J. Taylor, Alexander B. Parfenova, Liubov V. Samakai, Elsie Callaghan, Matthew M. Abarca-Heidemann, Karin Hart, P. John Rothberg, Brad S. TI Structure and function of multiple Ca2+-binding sites in a K+ channel regulator of K+ conductance (RCK) domain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE calcium; lipid bilayer; cooperativity ID POTASSIUM CHANNEL; GATING RING; CRYSTAL-STRUCTURES; SLO FAMILY; MTHK; MECHANISM; COMPLEX; BINDING; ACTIVATION; PROTEINS AB Regulator of K+ conductance (RCK) domains control the activity of a variety of K+ transporters and channels, including the human large conductance Ca2+-activated K+ channel that is important for blood pressure regulation and control of neuronal firing, and MthK, a prokaryotic Ca2+-gated K+ channel that has yielded structural insight toward mechanisms of RCK domain-controlled channel gating. In MthK, a gating ring of eight RCK domains regulates channel activation by Ca2+. Here, using electrophysiology and X-ray crystallography, we show that each RCK domain contributes to three different regulatory Ca2+-binding sites, two of which are located at the interfaces between adjacent RCK domains. The additional Ca2+-binding sites, resulting in a stoichiometry of 24 Ca2+ ions per channel, is consistent with the steep relation between [Ca2+] and MthK channel activity. Comparison of Ca2+-bound and unliganded RCK domains suggests a physical mechanism for Ca2+-dependent conformational changes that underlie gating in this class of channels. C1 [Pau, Victor P. T.; Smith, Frank J.; Samakai, Elsie; Callaghan, Matthew M.; Abarca-Heidemann, Karin; Rothberg, Brad S.] Temple Univ, Sch Med, Dept Biochem, Philadelphia, PA 19140 USA. [Taylor, Alexander B.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78240 USA. [Taylor, Alexander B.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Xray Crystallog Core Lab, San Antonio, TX 78240 USA. [Parfenova, Liubov V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78240 USA. [Hart, P. John] S Texas Vet Hlth Care Syst, Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78240 USA. RP Rothberg, BS (reprint author), Temple Univ, Sch Med, Dept Biochem, 3400 N Broad St, Philadelphia, PA 19140 USA. EM rothberg@temple.edu OI Rothberg, Brad/0000-0003-1982-2269 FU National Institutes of Health [GM068523]; Robert A. Welch Foundation [AQ1399]; American Heart Association FX We thank Daniel Yang and Andrew Thomson for helpful discussions, and the X-ray Core Facility of University of Texas Health Science Center at San Antonio for technical support. This research was supported by National Institutes of Health Grant GM068523 (to B. S. R) and Robert A. Welch Foundation Grant AQ1399 (to P.J.H.). V. P. P. has been supported by a postdoctoral fellowship from the American Heart Association, Great Rivers Affiliate. NR 29 TC 13 Z9 15 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 25 PY 2011 VL 108 IS 43 BP 17684 EP 17689 DI 10.1073/pnas.1107229108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 839OU UT WOS:000296378100033 PM 21997217 ER PT J AU Lim, PY Keating, JA Hoover, S Striker, R Bernard, KA AF Lim, Pei-Yin Keating, Julie A. Hoover, Spencer Striker, Rob Bernard, Kristen A. TI A Thiopurine Drug Inhibits West Nile Virus Production in Cell Culture, but Not in Mice SO PLOS ONE LA English DT Article ID DEPENDENT RNA-POLYMERASES; HEPATITIS-C VIRUS; 6-METHYLMERCAPTOPURINE RIBOSIDE; LIVER-TRANSPLANTATION; MYCOPHENOLIC-ACID; CHAIN-TERMINATORS; CRYSTAL-STRUCTURE; VIRAL LOAD; CDNA-CLONE; RIBAVIRIN AB Many viruses within the Flavivirus genus cause significant disease in humans; however, effective antivirals against these viruses are not currently available. We have previously shown that a thiopurine drug, 6-methylmercaptopurine riboside (6MMPr), inhibits replication of distantly related viruses within the Flaviviridae family in cell culture, including bovine viral diarrhea virus and hepatitis C virus replicon. Here we further examined the potential antiviral effect of 6MMPr on several diverse flaviviruses. In cell culture, 6MMPr inhibited virus production of yellow fever virus, dengue virus-2 (DENV-2) and West Nile virus (WNV) in a dose-dependent manner, and DENV-2 was significantly more sensitive to 6MMPr treatment than WNV. We then explored the use of 6MMPr as an antiviral against WNV in an immunocompetent mouse model. Once a day treatment of mice with 0.5 mg 6MMPr was just below the toxic dose in our mouse model, and this dose was used in subsequent studies. Mice were treated with 6MMPr immediately after subcutaneous inoculation with WNV for eight consecutive days. Treatment with 6MMPr exacerbated weight loss in WNV-inoculated mice and did not significantly affect mortality. We hypothesized that 6MMPr has low bioavailability in the central nervous system (CNS) and examined the effect of pre-treatment with 6MMPr on viral loads in the periphery and CNS. Pre-treatment with 6MMPr had no significant effect on viremia or viral titers in the periphery, but resulted in significantly higher viral loads in the brain, suggesting that the effect of 6MMPr is tissue-dependent. In conclusion, despite being a potent inhibitor of flaviviruses in cell culture, 6MMPr was not effective against West Nile disease in mice; however, further studies are warranted to reduce the toxicity and/or improve the bioavailability of this potential antiviral drug. C1 [Lim, Pei-Yin; Bernard, Kristen A.] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA. [Lim, Pei-Yin; Bernard, Kristen A.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Striker, Rob] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Keating, Julie A.; Hoover, Spencer; Striker, Rob] Univ Wisconsin, Dept Med, Madison, WI USA. RP Lim, PY (reprint author), Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA. EM kbernard@vetmed.wisc.edu FU National Institute of Allergy and Infectious Diseases; National Institutes of Health (NIH) [1U01-AI061193, 2T32AI007414]; Northeast Biodefence Center [U54-AI057158] FX This work was partially supported by federal funds from the National Institute of Allergy and Infectious Diseases, and the National Institutes of Health (NIH) under 1U01-AI061193. The BSL-3 animal core, which is funded in part by the Northeast Biodefence Center (U54-AI057158), was used for the animal studies conducted at the Wadsworth Center. JAK was supported by the NIH-funded Cellular and Molecular Parasitology Training Program (2T32AI007414). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 2 Z9 2 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 24 PY 2011 VL 6 IS 10 AR e26697 DI 10.1371/journal.pone.0026697 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 841MA UT WOS:000296515200043 PM 22039536 ER PT J AU Grady, D Berkowitz, SA AF Grady, Deborah Berkowitz, Seth A. TI Why Is a Good Clinical Prediction Rule So Hard to Find? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID IMPACT C1 [Grady, Deborah; Berkowitz, Seth A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94115 USA. [Grady, Deborah] San Francisco VA Med Ctr, San Francisco, CA USA. RP Grady, D (reprint author), Univ Calif San Francisco, Dept Med, 1635 Divisadero St,Ste 600, San Francisco, CA 94115 USA. EM Deborah.Grady@ucsf.edu NR 10 TC 17 Z9 18 U1 0 U2 8 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 OCT 24 PY 2011 VL 171 IS 19 BP 1701 EP 1702 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 837JX UT WOS:000296198200001 PM 22025427 ER PT J AU Deo, R Vittinghoff, E Lin, F Tseng, ZH Hulley, SB Shlipak, MG AF Deo, Rajat Vittinghoff, Eric Lin, Feng Tseng, Zian H. Hulley, Stephen B. Shlipak, Michael G. TI Risk Factor and Prediction Modeling for Sudden Cardiac Death in Women With Coronary Artery Disease SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; ANTIARRHYTHMIC-DRUG THERAPY; HEART-DISEASE; ESTROGEN/PROGESTIN REPLACEMENT; VENTRICULAR-ARRHYTHMIAS; POSTMENOPAUSAL WOMEN; EJECTION FRACTION; UNEXPECTED DEATH; RANDOMIZED-TRIAL; PREVENTION AB Background: To our knowledge, the risk of sudden cardiac death (SCD) and the assessment of risk factors in prediction models have not been evaluated in women with coronary artery disease (CAD). We sought to evaluate the incidence of SCD as well as its risk factors and their predictive accuracy among a population of women with CAD. Methods: The Heart and Estrogen/progestin Replacement Study evaluated the effects of hormone replacement therapy on cardiovascular events among 2763 postmenopausal women with CAD. Sudden cardiac death was defined as death resulting from a cardiac origin that occurred within 1 hour of symptom onset. The associations between candidate predictor variables and SCD were evaluated in a Cox proportional hazards model. The C-index was used to compare the predictive value of the clinical risk factors with left ventricular ejection fraction (LVEF) alone and in combination. The net reclassification improvement was also computed. Results: Over a mean follow-up of 6.8 years, SCD comprised 136 of the 254 cardiac deaths. The annual SCD event rate was 0.79% (95% confidence interval, 0.67-0.94). The following variables were independently associated with SCD in the multivariate model: myocardial infarction, heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m(2), atrial fibrillation, physical inactivity, and diabetes. The incidences of SCD among women with 0 (n = 683), 1 (n = 1224), 2 (n = 610), and 3 plus (n = 246) risk factors at baseline were 0.3%, 0.5%, 1.2%, and 2.9% per year, respectively. The combination of clinical risk factors and LVEF (C-index, 0.681) were better predictors of SCD than LVEF alone (C-index, 0.600) and resulted in a net reclassification improvement of 0.20 (P < .001). Conclusions: Sudden cardiac death comprised the majority of cardiac deaths among postmenopausal women with CAD. Independent predictors of SCD, including myocardial infarction, congestive heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m(2), atrial fibrillation, physical inactivity, and diabetes, improved SCD prediction when they were considered in addition to LVEF. C1 [Deo, Rajat] Univ Penn, Sect Electrophysiol, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Vittinghoff, Eric; Lin, Feng; Hulley, Stephen B.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Tseng, Zian H.] Univ Calif San Francisco, Cardiac Electrophysiol Sect, Div Cardiol, Dept Med, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Div Gen Internal Med, Dept Med, San Francisco, CA USA. RP Deo, R (reprint author), Univ Penn, Sect Electrophysiol, Div Cardiovasc Med, 3400 Spruce St,9 Founders Cardiol, Philadelphia, PA 19104 USA. EM Rajat.Deo@uphs.upenn.edu FU National Institutes of Health (NIH) [K23DK089118, R01 HL102090]; National Center for Research Resources, NIH [KL2 RR024132]; NIH Roadmap for Medical Research; Kynett-FOCUS Junior Faculty Investigator Award for Research in Women's Cardiovascular Health; Edna G. Kynett Memorial Foundation at the University of Pennsylvania School of Medicine FX Dr Deo was supported by grants K23DK089118 from the National Institutes of Health (NIH) and KL2 RR024132 from the National Center for Research Resources, a component of the NIH and NIH Roadmap for Medical Research. Additional grant support was obtained from a Kynett-FOCUS Junior Faculty Investigator Award for Research in Women's Cardiovascular Health funded by the Edna G. Kynett Memorial Foundation at the University of Pennsylvania School of Medicine. Dr Tseng is supported by grant R01 HL102090 from the NIH. NR 40 TC 16 Z9 16 U1 0 U2 3 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 OCT 24 PY 2011 VL 171 IS 19 BP 1703 EP 1709 DI 10.1001/archinternmed.2011.328 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 837JX UT WOS:000296198200002 PM 21788534 ER PT J AU Butt, AA Justice, AC Freiberg, MS AF Butt, Adeel A. Justice, Amy C. Freiberg, Matthew S. TI Risk of Heart Failure With Human Immunodeficiency Virus Is Greater Than Hypertension? Reply SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID INFECTION; DISEASE C1 [Butt, Adeel A.; Freiberg, Matthew S.] Univ Pittsburgh, Dept Med, Sch Med, Pittsburgh, PA 15213 USA. [Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. [Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. RP Butt, AA (reprint author), Univ Pittsburgh, Dept Med, Sch Med, 3601 5th Ave,Ste 3A, Pittsburgh, PA 15213 USA. EM butta@dom.pitt.edu NR 4 TC 0 Z9 0 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 OCT 24 PY 2011 VL 171 IS 19 BP 1773 EP 1774 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 837JX UT WOS:000296198200022 ER PT J AU Torterolo, P Ramos, OV Sampogna, S Chase, MH AF Torterolo, Pablo Ramos, Oscar V. Sampogna, Sharon Chase, Michael H. TI Hypocretinergic neurons are activated in conjunction with goal-oriented survival-related motor behaviors SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Orexin; Sleep; Motivation; Reward; Hypothalamus ID MESENCEPHALIC LOCOMOTOR REGION; HYPOTHALAMIC OREXIN NEURONS; SLEEP-WAKING CYCLE; C-FOS; SEXUAL-BEHAVIOR; LATERAL HYPOTHALAMUS; CANINE NARCOLEPSY; SELF-STIMULATION; LOCUS-COERULEUS; KNOCKOUT MICE AB Hypocretinergic neurons are located in the area of the lateral hypothalamus which is responsible for mediating goal-directed, survival-related behaviors. Consequently, we hypothesize that the hypocretinergic system functions to promote these behaviors including those patterns of somatomotor activation upon which they are based. Further, we hypothesize that the hypocretinergic system is not involved with repetitive motor activities unless they occur in conjunction with the goal-oriented behaviors that are governed by the lateral hypothalamus. In order to determine the veracity of these hypotheses, we examined Fos immunoreactivity (as a marker of neuronal activity) in hypocretinergic neurons in the cat during: a) Exploratory Motor Activity; b) Locomotion without Reward; c) Locomotion with Reward; and d) Wakefulness without Motor Activity. Significantly greater numbers of hypocretinergic neurons expressed c-fos when the animals were exploring an unknown environment during Exploratory Motor Activity compared with all other paradigms. In addition, a larger number of Hcrt + Fos + neurons were activated during Locomotion with Reward than during Wakefulness without Motor Activity. Finally, very few hypocretinergic neurons were activated during Locomotion without Reward and Wakefulness without Motor Activity, wherein there was an absence of goal-directed activities. We conclude that the hypocretinergic system does not promote wakefulness per se or motor activity per se but is responsible for mediating specific goal-oriented behaviors that take place during wakefulness. Accordingly, we suggest that the hypocretinergic system is responsible for controlling the somatomotor system and coordinating its activity with other systems in order to produce successful goal-oriented survival-related behaviors that are controlled by the lateral hypothalamus. (C) 2011 Elsevier Inc. All rights reserved. C1 [Ramos, Oscar V.; Sampogna, Sharon; Chase, Michael H.] WebSci Int, Los Angeles, CA 90024 USA. [Torterolo, Pablo; Chase, Michael H.] Univ Republica, Fac Med, Dept Fisiol, Montevideo, Uruguay. [Chase, Michael H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Chase, Michael H.] UCLA Sch Med, Dept Physiol, Los Angeles, CA USA. [Chase, Michael H.] UCLA Sch Med, Brain Res Inst, Los Angeles, CA USA. RP Chase, MH (reprint author), WebSci Int, 1251 Westwood Blvd, Los Angeles, CA 90024 USA. EM mchase@websciences.org FU USPHS [NS09999]; Brain Sciences Foundation FX This work was supported by USPHS Grant NS09999 and the Brain Sciences Foundation. NR 74 TC 10 Z9 11 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD OCT 24 PY 2011 VL 104 IS 5 BP 823 EP 830 DI 10.1016/j.physbeh.2011.07.032 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 837MP UT WOS:000296208200024 PM 21839102 ER PT J AU Arjomandi, M Frelinger, J Donde, A Wong, H Yellamilli, A Raymond, W AF Arjomandi, Mehrdad Frelinger, Jessica Donde, Aneesh Wong, Hofer Yellamilli, Amritha Raymond, Wilfred TI Secreted Osteopontin Is Highly Polymerized in Human Airways and Fragmented in Asthmatic Airway Secretions SO PLOS ONE LA English DT Article ID RHEUMATOID-ARTHRITIS; POSTTRANSLATIONAL MODIFICATIONS; STRUCTURAL REQUIREMENTS; INTEGRIN ALPHA-9-BETA-1; NEUTROPHIL INFILTRATION; TISSUE TRANSGLUTAMINASE; BOVINE OSTEOPONTIN; DEFICIENT MICE; CROSS-LINKING; MURINE MODEL AB Background: Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family and a cytokine with diverse biologic roles. OPN undergoes extensive post-translational modifications, including polymerization and proteolytic fragmentation, which alters its biologic activity. Recent studies suggest that OPN may contribute to the pathogenesis of asthma. Methodology: To determine whether secreted OPN (sOPN) is polymerized in human airways and whether it is qualitatively different in asthma, we used immunoblotting to examine sOPN in bronchoalveolar lavage (BAL) fluid samples from 12 healthy and 21 asthmatic subjects (and in sputum samples from 27 healthy and 21 asthmatic subjects). All asthmatic subjects had mild to moderate asthma and abstained from corticosteroids during the study. Furthermore, we examined the relationship between airway sOPN and cellular inflammation. Principal Findings: We found that sOPN in BAL fluid and sputum exists in polymeric, monomeric, and cleaved forms, with most of it in polymeric form. Compared to healthy subjects, asthmatic subjects had proportionately less polymeric sOPN and more monomeric and cleaved sOPN. Polymeric sOPN in BAL fluid was associated with increased alveolar macrophage counts in airways in all subjects. Conclusions: These results suggest that sOPN in human airways (1) undergoes extensive post-translational modification by polymerization and proteolytic fragmentation, (2) is more fragmented and less polymerized in subjects with mild to moderate asthma, and (3) may contribute to recruitment or survival of alveolar macrophages. C1 [Arjomandi, Mehrdad; Frelinger, Jessica] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. [Arjomandi, Mehrdad; Frelinger, Jessica; Donde, Aneesh; Wong, Hofer; Yellamilli, Amritha] Univ Calif San Francisco, Dept Med, Human Exposure Lab, San Francisco, CA USA. [Raymond, Wilfred] Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, San Francisco, CA 94143 USA. [Arjomandi, Mehrdad; Frelinger, Jessica; Raymond, Wilfred] San Francisco VA Med Ctr, Pulm Res Grp, San Francisco, CA USA. RP Arjomandi, M (reprint author), Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. EM mehrdad.arjomandi@ucsf.edu FU National Institutes of Health (NIH) [K23 HL083099, NIH P01 HL024136]; NIH/NCRR/OD [KL2 RR024130]; Northern California Institute for Research and Education; University of California San Francisco Cardiovascular Research Institute FX Funding: This work was supported by National Institutes of Health (NIH) K23 HL083099, NIH P01 HL024136, NIH/NCRR/OD UCSF-CTSI Grant Number KL2 RR024130, Northern California Institute for Research and Education, and University of California San Francisco Cardiovascular Research Institute Faculty Development Funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 69 TC 5 Z9 6 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 21 PY 2011 VL 6 IS 10 AR e25678 DI 10.1371/journal.pone.0025678 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 841LG UT WOS:000296513200005 PM 22031818 ER PT J AU Egede, LE Strom, JL Fernandes, J Knapp, RG Rojugbokan, A AF Egede, Leonard E. Strom, Joni L. Fernandes, Jyotika Knapp, Rebecca G. Rojugbokan, Adebola TI Effectiveness of technology-assisted case management in low income adults with Type 2 diabetes (TACM-DM): study protocol for a randomized controlled trial SO TRIALS LA English DT Article ID NURSE CASE-MANAGEMENT; PSYCHOMETRIC PROPERTIES; GLYCEMIC CONTROL; CARE MANAGEMENT; BLOOD-PRESSURE; SCALE; INTERVENTIONS; VETERANS; VALIDITY; OUTCOMES AB Background: An estimated 1 in 3 American adults will have diabetes by the year 2050. Nationally, South Carolina ranks 10(th) in cases of diagnosed diabetes compared to other states. In adults, type 2 diabetes (T2DM) accounts for approximately 90-95% of all diagnosed cases of diabetes. Clinically, provider and health system factors account for < 10% of the variance in major diabetes outcomes including hemoglobin A1c (HbA1c), lipid control, and resource use. Use of telemonitoring systems offer new opportunities to support patients with T2DM while waiting to be seen by their health care providers at actual office visits. A variety of interventions testing the efficacy of telemedicine interventions have been conducted, but the outcomes have yielded equivocal results, emphasizing the shortage of controlled, randomized trials in this area. This study provides a unique opportunity to address this gap in the literature by optimizing two strategies that have been shown to improve glycemic control, while simultaneously implementing clinical outcomes measures, using a sufficient sample size, and offering health care delivery to rural, underserved and low income communities with T2DM who are seen at Federally Qualified Health Centers (FQHCs) in coastal South Carolina. Methods: We describe a four-year prospective, randomized clinical trial, which will test the effectiveness of technology-assisted case management in low income rural adults with T2DM. Two-hundred (200) male and female participants, 18 years of age or older and with an HbA1c >= 8%, will be randomized into one of two groups: (1) an intervention arm employing the innovative FORA system coupled with nurse case management or (2) a usual care group. Participants will be followed for 6-months to ascertain the effect of the interventions on glycemic control. Our primary hypothesis is that among indigent, rural adult patients with T2DM treated in FQHC's, participants randomized to the technology-assisted case management intervention will have significantly greater reduction in HbA1c at 6 months of follow-up compared to usual care. Discussion: Results from this study will provide important insight into the effectiveness of technology-assisted case management intervention (TACM) for optimizing diabetes care in indigent, rural adult patients with T2DM treated in FQHC's. C1 [Egede, Leonard E.; Knapp, Rebecca G.] Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC 29401 USA. [Egede, Leonard E.; Strom, Joni L.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Dept Med, Charleston, SC 29425 USA. [Egede, Leonard E.; Strom, Joni L.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Fernandes, Jyotika] Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29425 USA. [Knapp, Rebecca G.] Med Univ S Carolina, Div Biostat & Epidemiol, Dept Med, Charleston, SC 29425 USA. [Rojugbokan, Adebola] Franklin C Fetter Family Hlth Ctr Inc, Charleston, SC 29403 USA. RP Egede, LE (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, 109 Bee St, Charleston, SC 29401 USA. EM egedel@musc.edu FU Department of Defense [W81XWH-10-2-0057]; Telemedicine & Advanced Technology Research Center (TATRC), Fort Detrick, Maryland [W81XWH-10-2-0057] FX The study is funded by Grant # W81XWH-10-2-0057 from the Department of Defense. This research and development project was conducted by the Medical University of South Carolina and is made possible by a cooperative agreement that was awarded and administered by the U.S. Army Medical Research and Material Command (USAMRMC) and the Telemedicine & Advanced Technology Research Center (TATRC), Fort Detrick, Maryland 21702, under Contract Number: W81XWH-10-2-0057. NR 41 TC 6 Z9 6 U1 0 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD OCT 20 PY 2011 VL 12 AR 231 DI 10.1186/1745-6215-12-231 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 849OF UT WOS:000297134200001 PM 22014122 ER PT J AU Kansagara, D Englander, H Salanitro, A Kagen, D Theobald, C Freeman, M Kripalani, S AF Kansagara, Devan Englander, Honora Salanitro, Amanda Kagen, David Theobald, Cecelia Freeman, Michele Kripalani, Sunil TI Risk Prediction Models for Hospital Readmission A Systematic Review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID QUALITY-OF-CARE; GENERAL MEDICINE PATIENTS; HEART-FAILURE; STATISTICAL-MODELS; PATIENT PREDICTORS; 30-DAY READMISSION; FOLLOW-UP; TRANSITIONS; PERFORMANCE; VALIDATION AB Context Predicting hospital readmission risk is of great interest to identify which patients would benefit most from care transition interventions, as well as to risk-adjust readmission rates for the purposes of hospital comparison. Objective To summarize validated readmission risk prediction models, describe their performance, and assess suitability for clinical or administrative use. Data Sources and Study Selection The databases of MEDLINE, CINAHL, and the Cochrane Library were searched from inception through March 2011, the EMBASE database was searched through August 2011, and hand searches were performed of the retrieved reference lists. Dual review was conducted to identify studies published in the English language of prediction models tested with medical patients in both derivation and validation cohorts. Data Extraction Data were extracted on the population, setting, sample size, follow-up interval, readmission rate, model discrimination and calibration, type of data used, and timing of data collection. Data Synthesis Of 7843 citations reviewed, 30 studies of 26 unique models met the inclusion criteria. The most common outcome used was 30-day readmission; only 1 model specifically addressed preventable readmissions. Fourteen models that relied on retrospective administrative data could be potentially used to risk-adjust readmission rates for hospital comparison; of these, 9 were tested in large US populations and had poor discriminative ability (c statistic range: 0.55-0.65). Seven models could potentially be used to identify high-risk patients for intervention early during a hospitalization (c statistic range: 0.56-0.72), and 5 could be used at hospital discharge (c statistic range: 0.68-0.83). Six studies compared different models in the same population and 2 of these found that functional and social variables improved model discrimination. Although most models incorporated variables for medical comorbidity and use of prior medical services, few examined variables associated with overall health and function, illness severity, or social determinants of health. Conclusions Most current readmission risk prediction models that were designed for either comparative or clinical purposes perform poorly. Although in certain settings such models may prove useful, efforts to improve their performance are needed as use becomes more widespread. JAMA. 2011;306(15):1688-1698 C1 [Kansagara, Devan; Freeman, Michele] Portland VA Med Ctr, VA Evidence Based Synth Program, Portland, OR 97239 USA. [Kansagara, Devan; Kagen, David] Portland VA Med Ctr, Dept Gen Internal Med, Portland, OR 97239 USA. [Kansagara, Devan; Englander, Honora; Kagen, David] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA. [Salanitro, Amanda] VA Tennessee Valley Healthcare Syst, Ctr Geriatr Res Educ & Clin, Nashville, TN USA. [Salanitro, Amanda; Theobald, Cecelia; Kripalani, Sunil] Vanderbilt Univ, Dept Med, Div Gen Internal Med & Publ Hlth, Sect Hosp Med, Nashville, TN USA. RP Kansagara, D (reprint author), Portland VA Med Ctr, VA Evidence Based Synth Program, Mailcode RD71,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM kansagar@ohsu.edu FU Department of Veterans Affairs; Veterans Health Administration, Office of Research and Development, Health Services Research and Development; National Center for Research Resources, National Institutes of Health [1 UL1 RR024976] FX This report is based on research conducted by the Evidence-Based Synthesis Program Center located at the Portland VA Medical Center, and funded by the Department of Veterans Affairs and the Veterans Health Administration, Office of Research and Development, Health Services Research and Development. The research also was funded in part by Vanderbilt CTSA grant 1 UL1 RR024976 from the National Center for Research Resources, National Institutes of Health. NR 62 TC 459 Z9 460 U1 8 U2 88 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 OCT 19 PY 2011 VL 306 IS 15 BP 1688 EP 1698 DI 10.1001/jama.2011.1515 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 834MA UT WOS:000295963200028 PM 22009101 ER PT J AU Kerlikowske, K Hubbard, RA Miglioretti, DL Geller, BM Yankaskas, BC Lehman, CD Taplin, SH Sickles, EA AF Kerlikowske, Karla Hubbard, Rebecca A. Miglioretti, Diana L. Geller, Berta M. Yankaskas, Bonnie C. Lehman, Constance D. Taplin, Stephen H. Sickles, Edward A. CA Breast Canc Surveillance Consortiu TI Comparative Effectiveness of Digital Versus Film-Screen Mammography in Community Practice in the United States A Cohort Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CANCER SURVEILLANCE CONSORTIUM; CARCINOMA IN-SITU; BREAST-CANCER; THERAPY USE; POPULATION; ACCURACY; DENSITY; PROGRAM; PERFORMANCE; WOMEN AB Background: Few studies have examined the comparative effectiveness of digital versus film-screen mammography in U. S. community practice. Objective: To determine whether the interpretive performance of digital and film-screen mammography differs. Design: Prospective cohort study. Setting: Mammography facilities in the Breast Cancer Surveillance Consortium. Participants: 329 261 women aged 40 to 79 years underwent 869 286 mammograms (231 034 digital; 638 252 film-screen). Measurements: Invasive cancer or ductal carcinoma in situ diagnosed within 12 months of a digital or film-screen examination and calculation of mammography sensitivity, specificity, cancer detection rates, and tumor outcomes. Results: Overall, cancer detection rates and tumor characteristics were similar for digital and film-screen mammography, but the sensitivity and specificity of each modality varied by age, tumor characteristics, breast density, and menopausal status. Compared with film-screen mammography, the sensitivity of digital mammography was significantly higher for women aged 60 to 69 years (89.9% vs. 83.0%; P = 0.014) and those with estrogen receptor-negative cancer (78.5% vs. 65.8%; P = 0.016); borderline significantly higher for women aged 40 to 49 years (82.4% vs. 75.6%; P = 0.071), those with extremely dense breasts (83.6% vs. 68.1%; P = 0.051), and pre- or perimenopausal women (87.1% vs. 81.7%; P = 0.057); and borderline significantly lower for women aged 50 to 59 years (80.5% vs. 85.1%; P = 0.097). The specificity of digital and film-screen mammography was similar by decade of age, except for women aged 40 to 49 years (88.0% vs. 89.7%; P < 0.001). Limitation: Statistical power for subgroup analyses was limited. Conclusion: Overall, cancer detection with digital or film-screen mammography is similar in U. S. women aged 50 to 79 years undergoing screening mammography. Women aged 40 to 49 years are more likely to have extremely dense breasts and estrogen receptor-negative tumors; if they are offered mammography screening, they may choose to undergo digital mammography to optimize cancer detection. C1 [Kerlikowske, Karla] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Washington, Sch Publ Hlth & Community Med, Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98195 USA. Univ Washington, Sch Med, Seattle, WA USA. Univ Vermont, Coll Med, Burlington, VT USA. Univ N Carolina, Chapel Hill, NC USA. NCI, Appl Res Program, Rockville, MD USA. RP Kerlikowske, K (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM Karla.Kerlikowske@ucsf.edu OI Hubbard, Rebecca/0000-0003-0879-0994 FU National Cancer Institute [U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040, R03CA150007, RC2CA148577] FX By the National Cancer Institute-funded BCSC cooperative agreement (grants U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, and U01CA70040) and National Cancer Institute grants R03CA150007 and RC2CA148577. The collection of cancer data used in this study was supported in part by several state public health departments and cancer registries throughout the United States; for a full description of these sources, see http://breastscreening.cancer.gov/work/acknowledgement.html. NR 30 TC 95 Z9 96 U1 1 U2 14 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 OCT 18 PY 2011 VL 155 IS 8 BP 493 EP U64 DI 10.7326/0003-4819-155-8-201110180-00005 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 835WB UT WOS:000296066300014 PM 22007043 ER PT J AU Chen, BB Glasser, JR Coon, TA Mallampalli, RK AF Chen, Bill B. Glasser, Jennifer R. Coon, Tiffany A. Mallampalli, Rama K. TI FBXL2 is a ubiquitin E3 ligase subunit that triggers mitotic arrest SO CELL CYCLE LA English DT Article DE F-box protein; centrosome; mitosis; cyclin D3; Aurora A ID CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; PROTEIN-KINASE; F-BOX; CHROMOSOMAL STABILITY; REGULATORY ENZYME; CYCLIN D3; DEGRADATION; EXPRESSION; IDENTIFICATION; CYTOKINESIS AB Mitotic progression is regulated by ubiquitin E3 ligase complexes to carefully orchestrate eukaryotic cell division. Here, we show that a relatively new E3 ligase component belonging to the SCF (Skip-Cullin1-F-box protein) E3 ligase family, SCF(FBXL2), impairs cell proliferation by mediating cyclin D3 polyubiquitination and degradation. Both cyclin D3 and FBXL2 colocalize within the centrosome. FBXL2 overexpression led to G(2)/M-phase arrest in transformed epithelia, resulting in the appearance of supernumerary centrosomes, tetraploidy and nuclei where condensed chromosomes are arranged on circular monopolar spindles typical of mitotic arrest. RNAi-mediated knockdown of cyclin D3 recapitulated effects of SCF(FBXL2) expression. SCF(FBXL2) impaired the ability of cyclin D3 to associate with centrosomal assembly proteins [ Aurora A, polo-like kinase 4 (Plk4), CDK11]. Thus, these results suggest a role for SCF(FBXL2) in regulating the fidelity of cellular division. C1 [Chen, Bill B.; Glasser, Jennifer R.; Coon, Tiffany A.; Mallampalli, Rama K.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. [Chen, Bill B.; Glasser, Jennifer R.; Coon, Tiffany A.; Mallampalli, Rama K.] Univ Pittsburgh, Acute Lung Injury Ctr Excellence, Pittsburgh, PA USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. RP Chen, BB (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. EM chenb@upmc.edu FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; US Department of Veterans Affairs; National Institutes of Health [HL096376, HL097376, HL098174] FX We thank A. F. Stewart for critical review of the manuscript and helpful suggestions. This material is based upon work supported, in part, by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. This work was supported by a Merit Review Award from the US Department of Veterans Affairs and National Institutes of Health R01 grants HL096376, HL097376 and HL098174 (to R. K. M.). The contents presented do not represent the views of the Department of Veterans Affairs or the United States Government. NR 36 TC 20 Z9 20 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 15 PY 2011 VL 10 IS 20 BP 3487 EP 3494 DI 10.4161/cc.10.20.17742 PG 8 WC Cell Biology SC Cell Biology GA 842DR UT WOS:000296570700026 PM 22024926 ER PT J AU Coldren, CD Miller, YE AF Coldren, Christopher D. Miller, York E. TI Progressive Endobronchial Premalignancy: Marked by Original CIN SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID LUNG-CANCER; PRENEOPLASTIC LESIONS; CHROMOSOMAL ANEUSOMY; FLUORESCENCE; EPITHELIUM C1 [Coldren, Christopher D.; Miller, York E.] Univ Colorado, Sch Med, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA. [Miller, York E.] Eastern Colorado Hlth Care Syst, Denver Vet Affairs Med Ctr, Denver, CO USA. RP Coldren, CD (reprint author), Univ Colorado, Sch Med, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA. FU NCI NIH HHS [CA 58187, P50 CA058187] NR 15 TC 1 Z9 1 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 15 PY 2011 VL 184 IS 8 BP 869 EP 870 DI 10.1164/rccm.201108-1476ED PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 835PG UT WOS:000296047700005 PM 22003147 ER PT J AU Rosales, KR Singh, G Wu, K Chen, J Janes, MR Lilly, MB Peralta, ER Siskind, LJ Bennett, MJ Fruman, DA Edinger, AL AF Rosales, Kimberly Romero Singh, Gurpreet Wu, Kevin Chen, Jie Janes, Matthew R. Lilly, Michael B. Peralta, Eigen R. Siskind, Leah J. Bennett, Michael J. Fruman, David A. Edinger, Aimee L. TI Sphingolipid-based drugs selectively kill cancer cells by down-regulating nutrient transporter proteins SO BIOCHEMICAL JOURNAL LA English DT Article DE AAL-149; autophagy; bioenergetics; FTY720; leukaemia; nutrient limitation ID SPHINGOSINE 1-PHOSPHATE; AEROBIC GLYCOLYSIS; ENDOTHELIAL-CELLS; CELLULAR-ENERGY; PROSTATE-CANCER; HEART-RATE; FTY720; APOPTOSIS; KINASE; GROWTH AB Cancer cells are hypersensitive to nutrient limitation because oncogenes constitutively drive glycolytic and TCA (tricarboxylic acid) cycle intermediates into biosynthetic pathways. As the anaplerotic reactions that replace these intermediates are fueled by imported nutrients, the cancer cell's ability to generate ATP becomes compromised under nutrient-limiting conditions. In addition, most cancer cells have defects in autophagy, the catabolic process that provides nutrients from internal sources when external nutrients are unavailable. Normal cells, in contrast, can adapt to the nutrient stress that kills cancer cells by becoming quiescent and catabolic. In the present study we show that FFY720, a water-soluble sphingolipid drug that is effective in many animal cancer models, selectively starves cancer cells to death by down-regulating nutrient transporter proteins. Consistent with a bioenergetic mechanism of action, FTY720 induced homoeostatic autophagy. Cells were protected from FTY720 by cell-permeant nutrients or by reducing nutrient demand, but blocking apoptosis was ineffective. Importantly, AAL-149, a FTY720 analogue that lacks FTY720's dose-limiting toxicity, also triggered transporter loss and killed patient-derived leukaemias while sparing cells isolated from normal donors. As they target the metabolic profile of cancer cells rather than specific oncogenic mutations, FTY720 analogues such as AAL-149 should be effective against many different tumour types, particularly in combination with drugs that inhibit autophagy. C1 [Rosales, Kimberly Romero; Singh, Gurpreet; Wu, Kevin; Peralta, Eigen R.; Edinger, Aimee L.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. [Chen, Jie; Bennett, Michael J.] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Janes, Matthew R.; Fruman, David A.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. [Janes, Matthew R.; Fruman, David A.] Univ Calif Irvine, Inst Immunol, Irvine, CA 92697 USA. [Lilly, Michael B.] Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 92697 USA. [Siskind, Leah J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Siskind, Leah J.] Med Univ S Carolina, Dept Med, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA. RP Edinger, AL (reprint author), Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. EM aedinger@uci.edu FU National Institutes for Health [F31 CA126494, P20 RR17677, K08 CA100526, R01 GM089919]; Gabrielle's Angel Foundation; University of California; Cancer Research Coordinating Committee (UC CRCC); University of California, Irvine; Council on Research Computing and Libraries (UCI CORCL); VA [CDA-2]; VA REAP; ACS [IRG 97-219-11] FX This work was supported by the National Institutes for Health [grant numbers F31 CA126494 (to K.R.R.), P20 RR17677, K08 CA100526 and R01 GM089919], the Gabrielle's Angel Foundation, the University of California, Cancer Research Coordinating Committee (UC CRCC), a Single Investigator Innovation Grant from the University of California, Irvine, Council on Research Computing and Libraries (UCI CORCL) to A.L.E., VA CDA-2, VA REAP and ACS [grant number IRG 97-219-11 (to L.J.S.)]. NR 66 TC 17 Z9 18 U1 0 U2 13 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 15 PY 2011 VL 439 BP 299 EP 311 DI 10.1042/BJ20110853 PN 2 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 836PO UT WOS:000296123800012 ER PT J AU Brody, AL Cook, IA AF Brody, Arthur L. Cook, Ian A. TI Manipulation of Cigarette Craving with Transcranial Magnetic Stimulation SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID BRAIN C1 [Brody, Arthur L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Greater Los Angeles Vet Affairs Smoking Cessat Pr, Los Angeles, CA 90095 USA. [Brody, Arthur L.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Greater Los Angeles Vet Affairs Smoking Cessat Pr, 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu FU NIDA NIH HHS [R01 DA20872, R01 DA020872] NR 10 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 2011 VL 70 IS 8 BP 702 EP 703 DI 10.1016/j.biopsych.2011.08.001 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 835HG UT WOS:000296026600003 PM 21967985 ER PT J AU Ito, H Pacold, IV Durazo-Arvizu, R Liu, K Shilipak, MG Goff, DC Tracy, RP Kramer, H AF Ito, Hiroki Pacold, Ivan V. Durazo-Arvizu, Ramon Liu, Kiang Shilipak, Michael G. Goff, David C., Jr. Tracy, Russell P. Kramer, Holly CA Multiethnic Study Atherosclerosis TI The Effect of Including Cystatin C or Creatinine in a Cardiovascular Risk Model for Asymptomatic Individuals SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cardiovascular diseases; creatinine; cystatin C; risk model ID CHRONIC KIDNEY-DISEASE; CORONARY-HEART-DISEASE; REACTIVE PROTEIN; MORTALITY; ASSOCIATION; PREDICTION; OLDER; ATHEROSCLEROSIS; STRATIFICATION; CLASSIFICATION AB The authors studied the incremental value of adding serum cystatin C or creatinine to the Framingham risk score variables (FRSVs) for the prediction of incident cardiovascular disease (CVD) among 6,653 adults without clinical CVD utilizing the Multi-Ethnic Study of Atherosclerosis (2000-2008). CVD events included coronary heart disease, heart failure, stroke, and peripheral arterial disease. Variables were transformed to yield optimal prediction of 6-year CVD events in sex-stratified models with FRSVs alone, FRSVs + cystatin C, and FRSVs + creatinine. Risk prediction in the 3 models was assessed by using the C statistic, and net reclassification improvement was calculated. The mean ages were 61.9 and 64.6 years for individuals with and without diabetes, respectively. After 6 years of follow-up, 447 (7.2%) CVD events occurred. In the total cohort, no significant change in the C statistic was noted with FRSVs + cystatin C and FRSVs + creatinine compared with FRSVs alone, and net reclassification improvement for CVD risk was extremely small and not significant with the addition of cystatin C or creatinine to FRSVs. Similar findings were noted after stratifying by baseline presence of diabetes. In conclusion, the addition of cystatin C or serum creatinine to FRSVs does not improve CVD risk prediction among adults without clinical CVD. C1 [Ito, Hiroki; Pacold, Ivan V.] Loyola Univ, Med Ctr, Div Cardiol, Dept Med, Maywood, IL 60153 USA. [Durazo-Arvizu, Ramon; Kramer, Holly] Loyola Univ, Med Ctr, Dept Prevent Med, Maywood, IL 60153 USA. [Liu, Kiang] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Shilipak, Michael G.] San Francisco VA Med Ctr, Dept Epidemiol & Biostat, San Francisco, CA USA. [Goff, David C., Jr.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol & Lab Med, Burlington, VT USA. RP Ito, H (reprint author), Loyola Univ, Med Ctr, Div Cardiol, Dept Med, 2160 S 1st Ave, Maywood, IL 60153 USA. EM itohiroki@gmail.com OI Kramer, Holly/0000-0002-6374-837X FU National Heart, Lung, and Blood Institute, Bethesda, Maryland [N01-HC-95159, N01-HC-95165, N01-HC-95167] FX This research was supported by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95167 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. NR 29 TC 13 Z9 14 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 15 PY 2011 VL 174 IS 8 BP 949 EP 957 DI 10.1093/aje/kwr185 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 830TI UT WOS:000295679700010 PM 21880578 ER PT J AU Tin, A Woodward, OM Kao, WHL Liu, CT Lu, XN Nalls, MA Shriner, D Semmo, M Akylbekova, EL Wyatt, SB Hwang, SJ Yang, Q Zonderman, AB Adeyemo, AA Palmer, C Meng, Y Reilly, M Shlipak, MG Siscovick, D Evans, MK Rotimi, CN Flessner, MF Kottgen, M Cupples, LA Fox, CS Kottgen, A AF Tin, Adrienne Woodward, Owen M. Kao, Wen Hong Linda Liu, Ching-Ti Lu, Xiaoning Nalls, Michael A. Shriner, Daniel Semmo, Mariam Akylbekova, Ermeg L. Wyatt, Sharon B. Hwang, Shih-Jen Yang, Qiong Zonderman, Alan B. Adeyemo, Adebowale A. Palmer, Cameron Meng, Yan Reilly, Muredach Shlipak, Michael G. Siscovick, David Evans, Michele K. Rotimi, Charles N. Flessner, Michael F. Koettgen, Michael Cupples, L. Adrienne Fox, Caroline S. Koettgen, Anna CA CARe & CHARGE Consortia TI Genome-wide association study for serum urate concentrations and gout among African Americans identifies genomic risk loci and a novel URAT1 loss-of-function allele SO HUMAN MOLECULAR GENETICS LA English DT Article ID URIC-ACID; CARDIOVASCULAR-DISEASE; GENETIC-LOCI; POPULATION; DESIGN; TRANSPORTER; FRAMINGHAM; GLUCOSE; SLC2A9; HEART AB Serum urate concentrations are highly heritable and elevated serum urate is a key risk factor for gout. Genome-wide association studies (GWAS) of serum urate in African American (AA) populations are lacking. We conducted a meta-analysis of GWAS of serum urate levels and gout among 5820 AA and a large candidate gene study among 6890 AA and 21 708 participants of European ancestry (EA) within the Candidate Gene Association Resource Consortium. Findings were tested for replication among 1996 independent AA individuals, and evaluated for their association among 28 283 EA participants of the CHARGE Consortium. Functional studies were conducted using (14)C-urate transport assays in mammalian Chinese hamster ovary cells. In the discovery GWAS of serum urate, three loci achieved genome-wide significance (P < 5.0 x 10(-8)): a novel locus near SGK1/SLC2A12 on chromosome 6 (rs9321453, P = 1.0 x 10(-9)), and two loci previously identified in EA participants, SLC2A9 (P = 3.8 x 10(-32)) and SLC22A12 (P = 2.1 x 10(-10)). A novel rare non-synonymous variant of large effect size in SLC22A12, rs12800450 (minor allele frequency 0.01, G65W), was identified and replicated (beta -1.19 mg/dl, P = 2.7 x 10(-16)). (14)C-urate transport assays showed reduced urate transport for the G65W URAT1 mutant. Finally, in analyses of 11 loci previously associated with serum urate in EA individuals, 10 of 11 lead single-nucleotide polymorphisms showed direction-consistent association with urate among AA. In summary, we identified and replicated one novel locus in association with serum urate levels and experimentally characterize the novel G65W variant in URAT1 as a functional allele. Our data support the importance of multi-ethnic GWAS in the identification of novel risk loci as well as functional variants. C1 [Koettgen, Anna] Freiburg Univ Hosp, Dept Med 4, Div Renal, D-79110 Freiburg, Germany. [Tin, Adrienne; Kao, Wen Hong Linda; Koettgen, Anna] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Woodward, Owen M.] Johns Hopkins Univ, Dept Physiol, Sch Med, Baltimore, MD 21205 USA. [Liu, Ching-Ti; Lu, Xiaoning; Cupples, L. Adrienne] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02118 USA. [Shriner, Daniel; Adeyemo, Adebowale A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Shriner, Daniel; Koettgen, Michael] Natl Human Genome Res Inst, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. [Akylbekova, Ermeg L.] Jackson State Univ, Jackson, MS 39213 USA. [Wyatt, Sharon B.] Univ Mississippi, Med Ctr, Sch Nursing, Jackson, MS 39216 USA. [Wyatt, Sharon B.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Hwang, Shih-Jen; Cupples, L. Adrienne; Fox, Caroline S.] NHLBI Framingham Heart Study, Framingham, MA 01702 USA. [Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Zonderman, Alan B.] NIA, Lab Personal & Cognit, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Reilly, Muredach] Univ Penn, Med Ctr, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Reilly, Muredach] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. [Siscovick, David] Univ Washington, Dept Med, Seattle, WA 98101 USA. [Evans, Michele K.] NIA, Hlth Dispar Res Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Palmer, Cameron] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Palmer, Cameron] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Palmer, Cameron] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Palmer, Cameron] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Palmer, Cameron; Meng, Yan] Broad Inst Harvard & MIT, Metab Dis Initiat, Cambridge, MA USA. [Flessner, Michael F.] NIDDK, KUH, NIH, Bethesda, MD 20892 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. RP Kottgen, A (reprint author), Freiburg Univ Hosp, Dept Med 4, Div Renal, Berliner Allee 29, D-79110 Freiburg, Germany. EM akottgen@jhsph.edu RI ; Kottgen, Anna/D-2920-2012; Yang, Qiong/G-5438-2014 OI Zonderman, Alan B/0000-0002-6523-4778; Cupples, L. Adrienne/0000-0003-0273-7965; Adeyemo, Adebowale/0000-0002-3105-3231 FU National Heart, Lung and Blood Institute; NIH, National Institute on Aging; National Center on Minority Health and Health Disparities [Z01-AG000513, 2009-149]; National Institutes of Health [S06GM008016-320107, S06GM008016-380111, 2M01RR010284]; Center for Research on Genomics and Global Health; National Human Genome Research Institute; National Institute of Diabetes and Digestive and Kidney Diseases; Center for Information Technology; Office of the Director at the National Institutes of Health [Z01HG200362]; NIDDK [DK032753-25A1]; German Research Foundation FX The authors wish to acknowledge the support of the National Heart, Lung and Blood Institute and the contributions of the research institutions, study investigators, field staff and study participants in creating this resource for biomedical research. We would like to thank Dr Yohannes Hagos who kindly provided the URAT1 plasmid, Dr H. Endou for the permission to use it, as well as Dr William B. Guggino for contributing experimental resources.; Healthy Aging in Neighborhoods of Diversity across the Life Span Study (HANDLS): this research was supported by the Intramural Research Program of the NIH, National Institute on Aging and the National Center on Minority Health and Health Disparities (intramural project # Z01-AG000513 and human subjects protocol # 2009-149). Data analyses for the HANDLS study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, Md. (http://biowulf.nih.gov).; Howard University Family Study (HUFS): The Howard University Family Study was supported by National Institutes of Health grants S06GM008016-320107 and S06GM008016-380111. Enrollment was carried out at the Howard University General Clinical Research Center, supported by National Institutes of Health grant 2M01RR010284. This research was supported in part by the Intramural Research Program of the Center for Research on Genomics and Global Health. The Center for Research on Genomics and Global Health is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology and the Office of the Director at the National Institutes of Health (Z01HG200362). Genotyping support was provided by the Coriell Institute for Medical Research. We thank the participants of the Howard University Family Study. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health.; Individual support: O.M.W. was supported by NIDDK: DK032753-25A1, A.K. was supported by the Emmy Noether Programme of the German Research Foundation. NR 53 TC 36 Z9 42 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 15 PY 2011 VL 20 IS 20 BP 4056 EP 4068 DI 10.1093/hmg/ddr307 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 824AN UT WOS:000295171200015 PM 21768215 ER PT J AU Cohen, DM Mittalhenkle, A Scott, DL Young, CJ Norman, DJ AF Cohen, David M. Mittalhenkle, Anuja Scott, David L. Young, Carlton J. Norman, Douglas J. TI African American Living-Kidney Donors Should Be Screened for APOL1 Risk Alleles SO TRANSPLANTATION LA English DT Article DE Genetics; Allele; Kidney ID STAGE RENAL-DISEASE; MYH9; TRANSPLANTATION; OUTCOMES; GENE AB The adjusted rate of end-stage kidney disease (ESKD) among African Americans is markedly increased relative to European Americans. African Americans are overrepresented on the kidney transplantation waiting list and experience longer wait times. In aggregate, these pressures drive recommendations for living donor transplantation. Genovese et al. recently implicated the APOL1 gene in ESKD risk among African Americans (Genovese et al. Science 2010; 329: 841). The presence of two APOL1 risk alleles doubles the relative risk for ESKD; moreover, the alleles are prevalent among African Americans. We propose a strategy for screening for the presence of APOL1 risk alleles among African American living kidney donors and for living-related donors for African American recipients. C1 [Cohen, David M.] Portland VA Med Ctr, Nephrol Sect, Portland, OR 97239 USA. [Cohen, David M.; Mittalhenkle, Anuja; Norman, Douglas J.] Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97201 USA. [Scott, David L.] Oregon Hlth & Sci Univ, Dept Surg, Div Liver & Pancreas Transplantat, Portland, OR 97201 USA. [Young, Carlton J.] Univ Alabama, Sch Med, Dept Surg, Div Transplantat, Birmingham, AL 35294 USA. RP Cohen, DM (reprint author), Portland VA Med Ctr, Nephrol Sect, Mailcode R&D 10,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM cohend@ohsu.edu FU Department of Veterans Affairs; National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health FX This work was supported by the Department of Veterans Affairs (D. M. C., A. M., and D. L. S.) and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (D.M.C.). NR 17 TC 26 Z9 26 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 15 PY 2011 VL 92 IS 7 BP 722 EP 725 DI 10.1097/TP.0b013e31822eec39 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 825YY UT WOS:000295319500006 PM 21878839 ER PT J AU Stenzel, D Lundkvist, A Sauvaget, D Busse, M Graupera, M van der Flier, A Wijelath, ES Murray, J Sobel, M Costell, M Takahashi, S Fassler, R Yamaguchi, Y Gutmann, DH Hynes, RO Gerhardt, H AF Stenzel, Denise Lundkvist, Andrea Sauvaget, Dominique Busse, Marta Graupera, Mariona van der Flier, Arjan Wijelath, Errol S. Murray, Jacqueline Sobel, Michael Costell, Mercedes Takahashi, Seiichiro Faessler, Reinhard Yamaguchi, Yu Gutmann, David H. Hynes, Richard O. Gerhardt, Holger TI Integrin-dependent and -independent functions of astrocytic fibronectin in retinal angiogenesis SO DEVELOPMENT LA English DT Article DE Angiogenesis; Tip cells; Extracellular matrix; Cell migration; Endothelial guidance ID ENDOTHELIAL-CELL MIGRATION; HEPARAN-SULFATE; EXTRACELLULAR-MATRIX; VASCULAR DEVELOPMENT; BIOLOGICAL-ACTIVITY; PRECURSOR CELLS; IN-VIVO; VEGF; EXPRESSION; GRADIENTS AB Fibronectin (FN) is a major component of the extracellular matrix and functions in cell adhesion, cell spreading and cell migration. In the retina, FN is transiently expressed and assembled on astrocytes (ACs), which guide sprouting tip cells and deposit a provisional matrix for sprouting angiogenesis. The precise function of FN in retinal angiogenesis is largely unknown. Using genetic tools, we show that astrocytes are the major source of cellular FN during angiogenesis in the mouse retina. Deletion of astrocytic FN reduces radial endothelial migration during vascular plexus formation in a gene dose-dependent manner. This effect correlates with reduced VEGF receptor 2 and PI3K/AKT signalling, and can be mimicked by selectively inhibiting VEGF-A binding to FN through intraocular injection of blocking peptides. By contrast, AC-specific replacement of the integrin-binding RGD sequence with FN-RGE or endothelial deletion of itga5 shows little effect on migration and PI3K/AKT signalling, but impairs filopodial alignment along AC processes, suggesting that FN-integrin alpha 5 beta 1 interaction is involved in filopodial adhesion to the astrocytic matrix. AC FN shares its VEGF-binding function and cell-surface distribution with heparan-sulfate (HS), and genetic deletion of both FN and HS together greatly enhances the migration defect, indicating a synergistic function of FN and HS in VEGF binding. We propose that in vivo the VEGF-binding properties of FN and HS promote directional tip cell migration, whereas FN integrin-binding functions to support filopodia adhesion to the astrocytic migration template. C1 [Stenzel, Denise; Lundkvist, Andrea; Sauvaget, Dominique; Busse, Marta; Gerhardt, Holger] London Res Inst Canc Res UK, Vasc Biol Lab, London WC2A 3PX, England. [Graupera, Mariona] Hosp Duran i Reynals 3 Planta, Oncol Mol Lab, Grp Angiogenesi, Inst Invest Biomed Bellvitge IDIBELL, Barcelona 08907, Spain. [van der Flier, Arjan; Hynes, Richard O.] MIT, Howard Hughes Med Inst, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Wijelath, Errol S.; Murray, Jacqueline; Sobel, Michael] Vet Affairs Puget Sound Hlth Care Syst, Div Vasc Surg, Dept Surg, Seattle, WA 98195 USA. [Wijelath, Errol S.; Murray, Jacqueline; Sobel, Michael] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Costell, Mercedes] Univ Valencia, Dept Bioquim & Biol Mol, E-46100 Burjassot, Spain. [Takahashi, Seiichiro; Faessler, Reinhard] Max Planck Inst Biochem, Dept Mol Med, D-82152 Martinsried, Germany. [Yamaguchi, Yu] Sanford Childrens Hlth Res Ctr, Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA. [Gutmann, David H.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Gerhardt, Holger] VIB, Vesalius Res Ctr, Vasc Patterning Lab, B-3000 Louvain, Belgium. RP Gerhardt, H (reprint author), London Res Inst Canc Res UK, Vasc Biol Lab, London WC2A 3PX, England. EM holger.gerhardt@cancer.org.uk RI Gerhardt, Holger/G-4610-2011 OI Gerhardt, Holger/0000-0001-9228-7472; Graupera, Mariona/0000-0003-4608-4185; Gerhardt, Holger/0000-0002-3030-0384 FU Cancer Research UK; EMBO; Lister Institute of Preventive Medicine; Leducq Transatlantic Network ARTEMIS; DFG; Max-Planck Society; National Institutes of Health [RO1 HL079182, PO1-HL66105]; NIGMS Cell Migration Consortium [GC11451.126452] FX This work was funded by Cancer Research UK, EMBO Young Investigator Program, The Lister Institute of Preventive Medicine, the Leducq Transatlantic Network ARTEMIS (H. G.), DFG and Max-Planck Society. This work was further supported by grants from the National Institutes of Health (RO1 HL079182 to M. S. and E. S. W., PO1-HL66105 and the NIGMS Cell Migration Consortium, GC11451.126452; A. F. Horwitz is the P. I.) and by the Howard Hughes Medical Institute of which R.O.H. is an Investigator. Deposited in PMC for release after 6 months. NR 47 TC 54 Z9 55 U1 0 U2 9 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT 15 PY 2011 VL 138 IS 20 BP 4451 EP 4463 DI 10.1242/dev.071381 PG 13 WC Developmental Biology SC Developmental Biology GA 822YD UT WOS:000295085600013 PM 21880786 ER PT J AU Liu, XH Yao, S Qiao, RF Levine, AC Kirschenbaum, A Pan, JP Wu, Y Qin, WP Bauman, WA Cardozo, CP AF Liu, Xin-Hua Yao, Shen Qiao, Rui-Fang Levine, Alice C. Kirschenbaum, Alexander Pan, Jiangping Wu, Yong Qin, Weiping Bauman, William A. Cardozo, Christopher P. TI Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Anabolic steroids; Muscle atrophy; Notch; Numb; Androgens; Nandrolone ID SKELETAL-MUSCLE; SATELLITE CELLS; TESTOSTERONE SUPPLEMENTATION; POSTNATAL MYOGENESIS; FIBER HYPERTROPHY; MEN; DIFFERENTIATION; KINASE; MOUSE; MODEL AB Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy. (C) 2011 Published by Elsevier Inc. C1 [Liu, Xin-Hua; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.] James J Peter VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C.; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Kirschenbaum, Alexander] Mt Sinai Sch Med, Dept Urol, New York, NY 10029 USA. RP Cardozo, CP (reprint author), James J Peter VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM chris.cardozo@mssm.edu FU Veterans Health Administration, Rehabilitation Research and Development Service [B4162C, B4616R, B3347 K] FX This work was supported by the Veterans Health Administration, Rehabilitation Research and Development Service (Grants B4162C, B4616R and B3347 K). NR 26 TC 6 Z9 8 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 14 PY 2011 VL 414 IS 1 BP 165 EP 169 DI 10.1016/j.bbrc.2011.09.048 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 837PH UT WOS:000296215200030 PM 21945932 ER PT J AU Kovac, A Erickson, MA Banks, WA AF Kovac, Andrej Erickson, Michelle A. Banks, William A. TI Brain microvascular pericytes are immunoactive in culture: cytokine, chemokine, nitric oxide, and LRP-1 expression in response to lipopolysaccharide SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE mouse brain pericytes; LPS; neurovascular unit; cytokines; chemokines; LRP-1; Alzheimers disease; nitric oxide ID RECEPTOR-RELATED PROTEIN-1; IL-12 P40 HOMODIMER; BLOOD-BRAIN; ALZHEIMERS-DISEASE; ENDOTHELIAL-CELLS; MICROGLIAL CELLS; CNS; BARRIER; MACROPHAGES; SURVIVAL AB Background: Brain microvascular pericytes are important constituents of the neurovascular unit. These cells are physically the closest cells to the microvascular endothelial cells in brain capillaries. They significantly contribute to the induction and maintenance of the barrier functions of the blood-brain barrier. However, very little is known about their immune activities or their roles in neuroinflammation. Here, we focused on the immunological profile of brain pericytes in culture in the quiescent and immune-challenged state by studying their production of immune mediators such as nitric oxide (NO), cytokines, and chemokines. We also examined the effects of immune challenge on pericyte expression of low density lipoprotein receptor-related protein-1 (LRP-1), a protein involved in the processing of amyloid precursor protein and the brain-to-blood efflux of amyloid-beta peptide. Methods: Supernatants were collected from primary cultures of mouse brain pericytes. Release of nitric oxide (NO) was measured by the Griess reaction and the level of S-nitrosylation of pericyte proteins measured with a modified "biotin-switch" method. Specific mitogen-activated protein kinase (MAPK) pathway inhibitors were used to determine involvement of these pathways on NO production. Cytokines and chemokines were analyzed by multianalyte technology. The expression of both subunits of LRP-1 was analyzed by western blot. Results: Lipopolysaccharide (LPS) induced release of NO by pericytes in a dose-dependent manner that was mediated through MAPK pathways. Nitrative stress resulted in S-nitrosylation of cellular proteins. Eighteen of twenty-three cytokines measured were released constitutively by pericytes or with stimulation by LPS, including interleukin (IL)-12, IL-13, IL-9, IL-10, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, eotaxin, chemokine (C-C motif) ligand (CCL)-3, and CCL-4. Pericyte expressions of both subunits of LRP-1 were upregulated by LPS. Conclusions: Our results show that cultured mouse brain microvascular pericytes secrete cytokines, chemokines, and nitric oxide and respond to the innate immune system stimulator LPS. These immune properties of pericytes are likely important in their communication within the neurovascular unit and provide a mechanism by which they participate in neuroinflammatory processes in brain infections and neurodegenerative diseases. C1 [Erickson, Michelle A.; Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Kovac, Andrej; Banks, William A.] Univ Washington, Div Gerontol & Geriatr Med, Dept Internal Med, Seattle, WA 98195 USA. [Erickson, Michelle A.; Banks, William A.] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA. [Kovac, Andrej] Slovak Acad Sci, Inst Neuroimmunol, Bratislava, Slovakia. RP Banks, WA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. EM wabanks1@uw.edu FU VA Merit Review [RO1 AG029839, R01 DK083485] FX Supported by VA Merit Review, RO1 AG029839, and R01 DK083485. NR 47 TC 56 Z9 56 U1 1 U2 13 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 OCT 13 PY 2011 VL 8 AR 139 DI 10.1186/1742-2094-8-139 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 841SF UT WOS:000296532700001 PM 21995440 ER PT J AU Singh, T Katiyar, SK AF Singh, Tripti Katiyar, Santosh K. TI Green Tea Catechins Reduce Invasive Potential of Human Melanoma Cells by Targeting COX-2, PGE(2) Receptors and Epithelial-to-Mesenchymal Transition SO PLOS ONE LA English DT Article ID NF-KAPPA-B; GRAPE SEED PROANTHOCYANIDINS; LUNG-CANCER; INFLAMMATORY RESPONSES; GUANYLATE-CYCLASE; PROSTAGLANDIN E-2; CARCINOMA-CELLS; NITRIC-OXIDE; SKIN-CANCER; DNA-REPAIR AB Melanoma is the most serious type of skin disease and a leading cause of death from skin disease due to its highly metastatic ability. To develop more effective chemopreventive agents for the prevention of melanoma, we have determined the effect of green tea catechins on the invasive potential of human melanoma cells and the molecular mechanisms underlying these effects using A375 (BRAF-mutated) and Hs294t (Non-BRAF-mutated) melanoma cell lines as an in vitro model. Employing cell invasion assays, we found that the inhibitory effects of green tea catechins on the cell migration were in the order of (-)-epigallocatechin-3-gallate (EGCG)>(-)-epigallocatechin >(-)-epicatechin-3-gallate >(-)-gallocatechin >(-)-epicatechin. Treatment of A375 and Hs294t cells with EGCG resulted in a dose-dependent inhibition of cell migration or invasion of these cells, which was associated with a reduction in the levels of cyclooxygenase (COX)-2, prostaglandin (PG) E-2 and PGE(2) receptors (EP2 and EP4). Treatment of cells with celecoxib, a COX-2 inhibitor, also inhibited melanoma cell migration. EGCG inhibits 12-O-tetradecanoylphorbol-13-acetate-, an inducer of COX-2, and PGE(2)-induced cell migration of cells. EGCG decreased EP2 agonist (butaprost)- and EP4 agonist (Cay10580)-induced cell migration ability. Moreover, EGCG inhibited the activation of NF-kappa B/p65, an upstream regulator of COX-2, in A375 melanoma cells, and treatment of cells with caffeic acid phenethyl ester, an inhibitor of NF-kappa B, also inhibited cell migration. Inhibition of melanoma cell migration by EGCG was associated with transition of mesenchymal stage to epithelial stage, which resulted in an increase in the levels of epithelial biomarkers (E-cadherin, cytokeratin and desmoglein 2) and a reduction in the levels of mesenchymal biomarkers (vimentin, fibronectin and N-cadherin) in A375 melanoma cells. Together, these results indicate that EGCG, a major green tea catechin, has the ability to inhibit melanoma cell invasion/migration, an essential step of metastasis, by targeting the endogenous expression of COX-2, PGE2 receptors and epithelial-to-mesenchymal transition. C1 [Singh, Tripti; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Nutr Obes Res Ctr, Birmingham, AL USA. [Katiyar, Santosh K.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Singh, T (reprint author), Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU National Center for Complementary and Alternative Medicine, NCCAM/NIH [5RO1 AT002536]; Veterans Administration FX This work was supported by funds from the 5RO1 AT002536 by National Center for Complementary and Alternative Medicine, NCCAM/NIH (SKK) (http//www.cancer.gov), and 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 37 TC 40 Z9 44 U1 2 U2 24 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 OCT 13 PY 2011 VL 6 IS 10 AR e25224 DI 10.1371/journal.pone.0025224 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 834QT UT WOS:000295978600011 PM 22022384 ER PT J AU Singh, JA Sperling, JW Cofield, RH AF Singh, Jasvinder A. Sperling, John W. Cofield, Robert H. TI Ninety day mortality and its predictors after primary shoulder arthroplasty: an analysis of 4,019 patients from 1976-2008 SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article DE mortality; shoulder arthroplasty; humeral head replacement; shoulder hemiarthroplasty ID BODY-MASS INDEX; TOTAL HIP-ARTHROPLASTY; 30-DAY MORTALITY; OBESITY PARADOX; OUTCOMES; REGISTRY; SURGERY; EVENTS; RISK AB Background: Examine 90-day postoperative mortality and its predictors following shoulder arthroplasty Methods: We identified vital status of all adults who underwent primary shoulder arthroplasty (Total shoulder arthroplasty (TSA) or humeral head replacement (HHR)) at the Mayo Clinic from 1976-2008, using the prospectively collected information from Total Joint Registry. We used univariate logistic regression models to assess the association of gender, age, body mass index, American Society of Anesthesiologist (ASA) class, Deyo-Charlson comorbidity index, an underlying diagnosis and implant fixation with odds of 90-day mortality after TSA or HHR. Multivariable models additionally adjusted for the type of surgery (TSA versus HHR). Adjusted Odds ratio (OR) with 95% confidence interval (CI) were calculated. Results: Twenty-eight of the 3, 480 patient operated died within 90-days of shoulder arthroplasty (0.8%). In multivariable-adjusted analyses, the following factors were associated with significantly higher odds of 90-day mortality: higher Deyo-Charlson index (OR, 1.54; 95% CI: 1.39, 1.70; p < 0.001); a diagnosis of tumor (OR, 16.2; 95% CI: 7.1, 36.7); and ASA class III (OR, 3.57; 95% CI: 1.29, 9.91; p = 0.01) or class IV (OR, 13.4; 95% CI: 2.44, 73.86; p = 0.003). BMI >= 30 was associated with lower risk of 90-day mortality (OR, 0.25; 95% CI: 0.08, 0.78). In univariate analyses, patients undergoing TSA had significantly lower 90-day mortality of 0.4% (8/2, 580) compared to 1% in HHR (20/1, 411) (odds ratio, 0.22 (95% CI: 0.10, 0.50); p = 0.0003). Conclusions: 90-day mortality following shoulder arthroplasty was low. An underlying diagnosis of tumor, higher comorbidity and higher ASA class were risk factors for higher 90-day mortality, while higher BMI was protective. Pre-operative comorbidity management may impact 90-day mortality following shoulder arthroplasty. A higher unadjusted mortality in patients undergoing TSA versus HHR may indicate the underlying differences in patients undergoing these procedures. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Sperling, John W.; Cofield, Robert H.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU National Institute of Health (NIH) (Mayo Clinic Center for Clinical and Translational Research) [1 KL2 RR024151-01] FX This material is the result of work supported with National Institute of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) and the resources and the use of facilities at the Birmingham VA Medical Center, Alabama, USA. We thank Scott Harmsen, MS and Cathy Schleck, BS for performing statistical analyses and Youlonda Lochler for providing the study cohort. NR 21 TC 23 Z9 23 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2474 J9 BMC MUSCULOSKEL DIS JI BMC Musculoskelet. Disord. PD OCT 12 PY 2011 VL 12 AR 231 DI 10.1186/1471-2474-12-231 PG 7 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 839OE UT WOS:000296376400002 PM 21992475 ER PT J AU Ehrlich, ME Gandy, S AF Ehrlich, Michelle E. Gandy, Sam TI Chromatin plasticity and the pathogenesis of Huntington disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID PROTEIN-1; ROLES C1 [Gandy, Sam] Mt Sinai Sch Med, Alzheimers Dis Res Ctr, Dept Neurol, New York, NY 10029 USA. Mt Sinai Sch Med, Alzheimers Dis Res Ctr, Dept Pediat, New York, NY 10029 USA. Mt Sinai Sch Med, Alzheimers Dis Res Ctr, Dept Psychiat, New York, NY 10029 USA. James J Peters VA Med Ctr, New York, NY 10029 USA. RP Gandy, S (reprint author), Mt Sinai Sch Med, Alzheimers Dis Res Ctr, Dept Neurol, New York, NY 10029 USA. EM samuel.gandy@mssm.edu FU NINDS NIH HHS [R01 NS059936] NR 16 TC 2 Z9 2 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 11 PY 2011 VL 108 IS 41 BP 16867 EP 16868 DI 10.1073/pnas.1113321108 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 834PD UT WOS:000295973800006 PM 21969556 ER PT J AU O'Hare, AM Choi, AI Boscardin, WJ Clinton, WL Zawadzki, I Hebert, PL Tamura, MK Taylor, L Larson, EB AF O'Hare, Ann M. Choi, Andy I. Boscardin, W. John Clinton, Walter L. Zawadzki, Ilan Hebert, Paul L. Tamura, Manjula Kurella Taylor, Leslie Larson, Eric B. TI LESS IS MORE Trends in Timing of Initiation of Chronic Dialysis in the United States SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CHRONIC KIDNEY-DISEASE; SURVIVAL; VALIDATION; MORTALITY; HARMFUL; GFR; AGE AB Background: During the past decade, a trend has been observed in the United States toward initiation of chronic dialysis at higher levels of estimated glomerular filtration rate. This likely reflects secular trends in the composition of the dialysis population and a tendency toward initiation of dialysis earlier in the course of kidney disease. Methods: The goal of this study was to generate model-based estimates of the magnitude of changes in the timing of dialysis initiation between 1997 and 2007. We used information from a national registry for end-stage renal disease on estimated glomerular filtration rate at initiation among patients who received their first chronic dialysis treatment in 1997 or 2007. We used information regarding predialysis estimated glomerular filtration rate slope from an integrated health care system. Results: After accounting for changes in the characteristics of new US dialysis patients from 1997 to 2007, we estimate that chronic dialysis was initiated a mean of 147 days earlier (95% confidence interval, 134-160) in the later compared with the earlier year. Differences in timing were consistent across a range of patient subgroups but were most pronounced for those aged 75 years or older; the mean difference in timing in that subgroup was 233 days (95% confidence interval, 206-267). Conclusions: Chronic dialysis appears to have been initiated substantially earlier in the course of kidney disease in 2007 compared with 1997. In the absence of strong evidence to suggest that earlier initiation of chronic dialysis is beneficial, these findings call for careful evaluation of contemporary dialysis initiation practices in the United States. C1 [O'Hare, Ann M.] Univ Washington, Dept Med, Seattle, WA USA. [Hebert, Paul L.] Univ Washington, Dept Hlth Sci, Seattle, WA USA. [O'Hare, Ann M.] Vet Affairs VA Med Ctr, Seattle, WA USA. [O'Hare, Ann M.] Renal Dialysis Unit, Seattle, WA USA. [Hebert, Paul L.; Taylor, Leslie] VA Puget Sound Healthcare Syst, VA Hlth Serv, Res & Dev Ctr Excellence, Seattle, WA USA. [O'Hare, Ann M.; Clinton, Walter L.; Zawadzki, Ilan; Larson, Eric B.] Grp Hlth Cooperat Puget Sound, Seattle, WA USA. [O'Hare, Ann M.; Clinton, Walter L.; Zawadzki, Ilan; Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA USA. [Choi, Andy I.; Boscardin, W. John] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Choi, Andy I.; Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Tamura, Manjula Kurella] Stanford Univ, Dept Med, San Francisco, CA USA. [Tamura, Manjula Kurella] VA Palo Alto Healthcare Syst, San Francisco, CA USA. [Choi, Andy I.] VA Med Ctr, VA No Calif Healthcare Syst, San Francisco, CA USA. RP O'Hare, AM (reprint author), Vet Affairs Med Ctr, Renal Dialysis Unit, 1660 S Columbian Way, Seattle, WA 98109 USA. EM ann.ohare@va.gov RI Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 FU American Federation for Aging Research [K23DK080645, K23AG028952]; National Institute on Aging; National Institutes of Health; Beeson Career Development Award [K23AG28980] FX Dr O'Hare serves as the principal investigator for an interagency agreement between the Centers for Disease Control and Prevention and the Veterans Affairs Puget Sound Healthcare System. Within the past year, she has received royalties from UpToDate, Inc. Dr Choi was supported by grant K23DK080645 and Dr Kurella Tamura was supported by grant K23AG028952 (a Paul B. Beeson Career Development Award) from the American Federation for Aging Research and the National Institute on Aging. Dr Larson has received research support from the National Institutes of Health; royalties from UpToDate, Inc; Springer Publishing Company; and Elsevier BV; and speaker honoraria from universities and other nonprofit organizations.; This study was supported by Beeson Career Development Award K23AG28980 (principal investigator: Dr O'Hare). NR 32 TC 30 Z9 30 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 OCT 10 PY 2011 VL 171 IS 18 BP 1663 EP 1669 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 830YL UT WOS:000295695600012 PM 21987197 ER PT J AU Rao, SV Kaltenbach, LA Weintraub, WS Roe, MT Brindis, RG Rumsfeld, JS Peterson, ED AF Rao, Sunil V. Kaltenbach, Lisa A. Weintraub, William S. Roe, Matthew T. Brindis, Ralph G. Rumsfeld, John S. Peterson, Eric D. TI Prevalence and Outcomes of Same-Day Discharge After Elective Percutaneous Coronary Intervention Among Older Patients SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SINGLE-CENTER EXPERIENCE; DAY HOME DISCHARGE; STENT IMPLANTATION; ANGIOPLASTY; OUTPATIENT; FEASIBILITY; SAFETY; STAY; TRENDS; BOLUS AB Context Patients undergoing elective percutaneous coronary intervention (PCI) are generally observed overnight in the hospital. The association between same-day discharge of older patients and death or readmission is unclear. Objective To evaluate the prevalence and outcomes of same-day discharge among older patients undergoing elective PCI in the United States. Design, Setting, and Participants Multicenter cohort study. Data were from 107 018 patients 65 years or older undergoing elective PCI procedures at 903 sites participating in the CathPCI Registry between November 2004 and December 2008 and were linked with Medicare Part A claims. Patients were divided into 2 groups based on their length of stay after PCI: same-day discharge or overnight stay. Main Outcome Measures Death or rehospitalization occurring within 2 days and by 30 days after PCI. Results The prevalence of same-day discharge was 1.25% (95% CI, 1.19%-1.32%; n = 1339 patients) with significant variation across facilities. Patient characteristics were similar between the 2 groups, although same-day discharge patients underwent shorter procedures with less multivessel intervention. There were no significant differences in the rates of death or rehospitalization at 2 days (same-day discharge, 0.37% [95% CI, 0.16%-0.87%] vs overnight stay, 0.50% [95% CI, 0.46%-0.54%]; P = .51) or at 30 days (same-day discharge, 9.63% [95% CI, 8.17%-11.33%] vs overnight stay, 9.70% [95% CI, 9.52%-9.88%]; P = .94). Among patients with adverse outcomes, the median time to death or rehospitalization did not differ significantly between the groups (same-day discharge, 13 days [interquartile range, 7.0-21.0] vs overnight stay, 14 days [interquartile range, 7.0-21.0]; P = .96). After adjustment for patient and procedure characteristics, same-day discharge was not significantly associated with 30-day death or rehospitalization (adjusted odds ratio, 0.95 [95% CI, 0.78-1.16]). Conclusion Among selected low-risk Medicare patients undergoing elective PCI, same-day discharge is rarely implemented but is not associated with death or rehospitalization compared with overnight observation. JAMA. 2011;306(13):1461-1467 C1 [Rao, Sunil V.; Kaltenbach, Lisa A.; Roe, Matthew T.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC 27705 USA. [Weintraub, William S.] Christiana Care Hosp, Newark, DE USA. [Brindis, Ralph G.] No Calif Kaiser Permanente, Oakland, CA USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. RP Rao, SV (reprint author), Duke Clin Res Inst, 508 Fulton St 111A, Durham, NC 27705 USA. EM sunil.rao@duke.edu FU Terumo Medical; Medicines Company; AstraZeneca; Zoll; Ikaria; sanofi-aventis; Otsuka; Bristol-Myers Squibb; Abbott; Eli Lilly; Shionogi; Cardionet; Daiichi-Sankyo; Roche; Novartis; Merck-Schering Plough; American College of Cardiology; American Heart Association; GlaxoSmithKline; KAI Pharmaceuticals; Orexigen; Helsinn Pharmaceuticals; Regeneron; Schering Plough/Merck; Johnson Johnson; St Jude Inc; Bayer; Pfizer; American College of Cardiology Foundation National Cardiovascular Data Registry (NCDR) FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Rao reported receiving consulting fees from Terumo Medical, The Medicines Company, AstraZeneca, and Zoll and research funding from Ikaria, sanofi-aventis, and Terumo Medical. Dr Weintraub reported receiving research grants from Otsuka, AstraZeneca, Bristol-Myers Squibb, sanofi-aventis, and Abbott; receiving consultant fees from Eli Lilly, Bristol-Myers Squibb, Shionogi, sanofi-aventis, Cardionet, and Daiichi-Sankyo; and providing expert testimony in cases involving Bayer and Pfizer. Dr Roe reported receiving research funding from Eli Lilly, Roche, Novartis, Merck-Schering Plough, Bristol-Myers Squibb, the American College of Cardiology, and the American Heart Association and consulting fees/honoraria from GlaxoSmithKline, KAI Pharmaceuticals, Novartis, Eli Lilly, Bristol-Myers Squibb, sanofi-aventis, Merck, Orexigen, Helsinn Pharmaceuticals, Regeneron, and AstraZeneca. Dr Rumsfeld reported being chief science officer for the National Cardiovascular Data Registry. Dr Peterson reported receiving research grants from Bristol-Myers Squibb, sanofi-aventis, Eli Lilly, Schering Plough/Merck, Johnson & Johnson, and St Jude Inc and consultant fees from Bayer and Pfizer. No other disclosures were reported.; This analysis was funded by the American College of Cardiology. This research was supported by the American College of Cardiology Foundation National Cardiovascular Data Registry (NCDR). NR 25 TC 41 Z9 43 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 5 PY 2011 VL 306 IS 13 BP 1461 EP 1467 DI 10.1001/jama.2011.1409 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 828MZ UT WOS:000295506900025 PM 21972308 ER PT J AU Lee, SJ Walter, LC AF Lee, Sei J. Walter, Louise C. TI Quality Indicators for Older Adults Preventing Unintended Harms SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID PRACTICE GUIDELINES; OF-CARE; CANCER; PERFORMANCE; LESSONS C1 [Lee, Sei J.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Lee, SJ (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement St,Bldg 1,Room 211A, San Francisco, CA 94121 USA. EM sei.lee@ucsf.edu FU NCI NIH HHS [1R01CA134425, R01 CA134425]; NCRR NIH HHS [KL2 RR024130-02, KL2 RR024130]; NIA NIH HHS [K23 AG040779] NR 10 TC 19 Z9 19 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 OCT 5 PY 2011 VL 306 IS 13 BP 1481 EP 1482 DI 10.1001/jama.2011.1418 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 828MZ UT WOS:000295506900028 PM 21972311 ER PT J AU Nery, FG Matsuo, K Nicoletti, MA Monkul, ES Zunta-Soares, GB Hatch, JP Lafer, B Soares, JC AF Nery, Fabiano G. Matsuo, Koji Nicoletti, Mark A. Monkul, E. Serap Zunta-Soares, Giovana B. Hatch, John P. Lafer, Beny Soares, Jair C. TI Association between prior alcohol use disorders and decreased prefrontal gray matter volumes in bipolar I disorder patients SO NEUROSCIENCE LETTERS LA English DT Article DE Bipolar disorder; Alcoholism; Comorbidity; Physiopathology; Cerebral cortex; Magnetic resonance imaging ID ORBITOFRONTAL CORTEX; BRAIN; ABNORMALITIES; COMORBIDITY; DEPENDENCE; COCAINE; MRI AB Up to 50% of bipolar disorder (BD) patients present a lifetime diagnosis of alcohol use disorders (AUD). BD patients with comorbid AUD, even when in remission from the AUD, have a poorer outcome and functional impairment than patients with BD alone. The neurobiological abnormalities that potentially characterize this severe subgroup of BD patients are unknown. Our goal was to investigate gray matter (GM) volume abnormalities in BD I patients with comorbid AUD. Twenty-one BD-AUD patients, 21 BD-nonAUD BD patients, and 25 healthy controls (HC), matched by age, gender, and handedness were studied. The BD-AUD patients were in remission from AUD on average for 6.8 years. 3D SPGR MRIs (TR = 25 ms, TE = 5 ms, slice thickness = 1.5 mm) were acquired from all subjects using a 1.5 T GE Signa Imaging System. We used an optimized voxel-based morphometry protocol to compare GM volumes among the groups. BD-AUD patients presented smaller GM volumes in the left medial frontal and the right anterior cingulate gyri compared to BD-nonAUD patients. BDnon-AUD patients did not present GM volume differences compared to HC. These findings provide evidence for an effect of comorbid AUD on regional brain structure of BD I patients and warrant further research on neurobiological aspects of this prevalent and severe comorbidity. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Nery, Fabiano G.; Monkul, E. Serap; Hatch, John P.; Lafer, Beny] Univ Sao Paulo, Sch Med, Bipolar Disorder Program PROMAN, Dept Psychiat, Sao Paulo, Brazil. [Nery, Fabiano G.; Matsuo, Koji; Monkul, E. Serap] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Nery, Fabiano G.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Matsuo, Koji] Yamaguchi Univ, Div Neuropsychiat, Dept Neurosci, Grad Sch Med, Yamaguchi, Japan. [Nicoletti, Mark A.; Zunta-Soares, Giovana B.; Soares, Jair C.] Univ Texas Med Sch, Dept Psychiat & Behav Sci, Houston, TX USA. [Hatch, John P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Orthodont, San Antonio, TX 78229 USA. RP Soares, JC (reprint author), UT Houston Med Sch, Dept Psychiat & Behav Sci, 1300 Moursund St, Houston, TX 77030 USA. EM jair.c.soares@uth.tmc.edu RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 FU UTHSCSA GCRC [M01-RR-01346]; Krus Endowed Chair in Psychiatry (UTHSCSA); Veterans Administration (VA Merit Review); KAKENHI-C [21591519]; [MH 01736]; [MH 068662]; [RR 020571] FX This research was partly supported, by grants MH 01736, MH 068662, RR 020571, UTHSCSA GCRC (M01-RR-01346), the Krus Endowed Chair in Psychiatry (UTHSCSA), the Veterans Administration (VA Merit Review), KAKENHI-C 21591519 (to K. Matsuo) and a private donation from Thompson Mottais family (to PROMAN). E. Serap Monkul is an employee of Eli Lilly Brazil. The other authors do not have any commercial associations that might pose a conflict of interest in connection with this manuscript. NR 32 TC 10 Z9 10 U1 1 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 3 PY 2011 VL 503 IS 2 BP 136 EP 140 DI 10.1016/j.neulet.2011.08.026 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 836NN UT WOS:000296118500012 PM 21884753 ER PT J AU Leong, JVB Boro, MS Winter, ME AF Leong, Julie V. B. Boro, Maureen S. Winter, Michael E. TI Vancomycin clearance in overweight and obese patients SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Letter ID PHARMACOKINETICS C1 [Leong, Julie V. B.; Boro, Maureen S.] San Francisco VA Med Ctr, Pharm Informat & Pharmacokinet Program, San Francisco, CA 94121 USA. [Winter, Michael E.] Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA. RP Leong, JVB (reprint author), San Francisco VA Med Ctr, Pharm Informat & Pharmacokinet Program, 4150 Clement St, San Francisco, CA 94121 USA. EM maureen.boro@va.gov NR 4 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD OCT 1 PY 2011 VL 68 IS 19 BP 1777 EP 1778 DI 10.2146/ajhp110286 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 941FG UT WOS:000303948500011 ER PT J AU Ioannou, GN Boyko, EJ AF Ioannou, George N. Boyko, Edward J. TI Metformin and Colorectal Cancer Risk in Diabetic Patients SO DIABETES CARE LA English DT Editorial Material ID BREAST-CANCER; EUROPEAN ASSOCIATION; CONSENSUS ALGORITHM; MEDICAL-MANAGEMENT; METABOLIC SYNDROME; TYPE-2; THERAPY; HYPERGLYCEMIA; METAANALYSIS; ADJUSTMENT C1 [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, Seattle, WA USA. [Ioannou, George N.; Boyko, Edward J.] Univ Washington, Seattle, WA 98195 USA. [Ioannou, George N.; Boyko, Edward J.] Vet Affaiis Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Div Internal Med, Dept Med, Seattle, WA USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, Seattle, WA USA. EM georgei@medicine.washington.edu OI Boyko, Edward/0000-0002-3695-192X NR 17 TC 7 Z9 7 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2011 VL 34 IS 10 BP 2336 EP 2337 DI 10.2337/dc11-1447 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 910AG UT WOS:000301609000040 PM 21949227 ER PT J AU Velayos-Baeza, A Holinski-Feder, E Neitzel, B Bader, B Critchley, EMR Monaco, AP Danek, A Walker, RH AF Velayos-Baeza, Antonio Holinski-Feder, Elke Neitzel, Birgit Bader, Benedikt Critchley, Edmund M. R. Monaco, Anthony P. Danek, Adrian Walker, Ruth H. TI Chorea-Acanthocytosis Genotype in the Original Critchley Kentucky Neuroacanthocytosis Kindred SO ARCHIVES OF NEUROLOGY LA English DT Article ID GENE; PROTEIN; DISEASE AB Objective: To determine the molecular nature of the neurological disease in the seminal family reported by Critchley et al in the 1960s, characterized by a hyperkinetic movement disorder and the appearance of acanthocytosis on peripheral blood smear. The eponym Levine-Critchley syndrome, subsequently termed neuroacanthocytosis, has been applied to symptomatically similar, but genetically distinct, disorders, resulting in clinical and diagnostic confusion. Design: DNA analysis. Setting: Molecular biology research laboratories. Participants: First- and second-degree relatives of the original Critchley et al proband from Kentucky. Main Outcome Measures: Mutations in the VPS13A gene. Results: A mutation was identified in the VPS13A gene, responsible for autosomal recessive chorea-acanthocytosis. Haplotype reconstruction suggested that this mutation was homozygous in the proband. Conclusion: These findings strongly support the diagnosis of chorea-acanthocytosis as the disorder described in the original report. C1 [Walker, Ruth H.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA. [Walker, Ruth H.] Mt Sinai Sch Med, New York, NY USA. [Velayos-Baeza, Antonio; Monaco, Anthony P.] Wellcome Trust Ctr Human Genet, Oxford, England. [Critchley, Edmund M. R.] Univ Cent Lancashire, Preston PR1 2HE, Lancs, England. [Holinski-Feder, Elke; Neitzel, Birgit] Med Genet Zentrum, Munich, Germany. [Bader, Benedikt; Danek, Adrian] Univ Munich, Neurol Klin & Poliklin, Munich, Germany. RP Walker, RH (reprint author), James J Peters Vet Affairs Med Ctr, Dept Neurol 127, Bronx, NY 10468 USA. EM ruth.walker@mssm.edu RI Danek, Adrian/G-7339-2011; Monaco, Anthony/A-4495-2010 OI Danek, Adrian/0000-0001-8857-5383; Monaco, Anthony/0000-0001-7480-3197 FU Mary Kinross Charitable Trust and the Chaney family; Wellcome Trust [075491/Z/04] FX This work was supported by a grant from the Advocacy for Neuroacanthocytosis Patients (the Mary Kinross Charitable Trust and the Chaney family) (Drs Velayos-Baeza and Monaco) and grant 075491/Z/04 from the Wellcome Trust (Drs Velayos-Baeza and Monaco). NR 14 TC 1 Z9 1 U1 0 U2 1 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 OCT PY 2011 VL 68 IS 10 BP 1330 EP 1333 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 830YV UT WOS:000295696700018 PM 21987550 ER PT J AU Bunchorntavakul, C Siripun, A Chavalitdhamrong, D AF Bunchorntavakul, Chalermrat Siripun, Aroon Chavalitdhamrong, Disaya TI Fluvastatin Monotherapy for the Treatment of Patients with Chronic Hepatitis C: A Randomized Double-Blinded Placebo-Controlled Study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 76th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 28-NOV 02, 2011 CL Washington, DC SP Amer Coll Gastroenterol C1 [Bunchorntavakul, Chalermrat; Siripun, Aroon] Rangsit Univ, Fac Med, Rajavithi Hosp, Bangkok, Thailand. [Chavalitdhamrong, Disaya] Mt Sinai Sch Med, James J Peters Vet Affairs Med Ctr, Bronx, NY USA. NR 0 TC 2 Z9 2 U1 0 U2 2 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 OCT PY 2011 VL 106 SU 2 MA 259 BP S102 EP S103 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 885II UT WOS:000299772000260 ER PT J AU Leung, F AF Leung, Felix TI Injection Treatment for Fecal Incontinence (FI) - Review of Impact on Quality-of-life (QoL) Measures SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 76th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 28-NOV 02, 2011 CL Washington, DC SP Amer Coll Gastroenterol C1 [Leung, Felix] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, North Hills, CA USA. [Leung, Felix] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 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 OCT PY 2011 VL 106 SU 2 MA 1319 BP S503 EP S503 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 885II UT WOS:000299772002162 ER PT J AU Okeke, F Korsten, M Shaw, S Hunt, K Rosman, A AF Okeke, Francis Korsten, Mark Shaw, Spencer Hunt, Kristel Rosman, Alan TI Safety of Propofol Used as a Rescue Agent During Colonoscopy SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 76th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 28-NOV 02, 2011 CL Washington, DC SP Amer Coll Gastroenterol C1 [Okeke, Francis; Korsten, Mark; Shaw, Spencer; Hunt, Kristel; Rosman, Alan] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 OCT PY 2011 VL 106 SU 2 MA 402 BP S157 EP S158 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 885II UT WOS:000299772000399 ER PT J AU Salazar, C Cardenas, V Reddy, R Graham, D AF Salazar, Cesar Cardenas, Victor Reddy, Rita Graham, David TI Helicobacter pylori Eradication Using a 14-day Bismuth Quadruple Therapy Among Hispanic Adults in El Paso, Texas: Preliminary Findings SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 76th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 28-NOV 02, 2011 CL Washington, DC SP Amer Coll Gastroenterol C1 [Cardenas, Victor] Univ Texas Sch Publ Hlth, El Paso, TX USA. [Reddy, Rita; Graham, David] DeBakey Vet Affairs Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 OCT PY 2011 VL 106 SU 2 MA 118 BP S47 EP S48 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 885II UT WOS:000299772000119 ER PT J AU Spiegel, B Poysophon, P Snyder, B Agarwal, N Yen, L Hodgkins, P Cohen, E Vu, M Kurzbard, N Atia, M Sheen, V Kaneshiro, M Fuller, G Bolus, R AF Spiegel, Brennan Poysophon, Poyrung Snyder, Bradley Agarwal, Nikhil Yen, Linette Hodgkins, Paul Cohen, Erica Vu, Michelle Kurzbard, Nicole Atia, Mary Sheen, Victoria Kaneshiro, Marc Fuller, Garth Bolus, Roger TI Direct Costs and Resource Utilization for Inpatient Diverticulitis Admissions SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 76th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 28-NOV 02, 2011 CL Washington, DC SP Amer Coll Gastroenterol C1 [Spiegel, Brennan] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Snyder, Bradley; Kurzbard, Nicole] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Yen, Linette; Hodgkins, Paul] Shire Dev Inc, Global Hlth Econ Outcomes Res & Epidemiol, Los Angeles, CA USA. [Agarwal, Nikhil; Cohen, Erica; Vu, Michelle; Atia, Mary; Sheen, Victoria; Kaneshiro, Marc; Fuller, Garth; Bolus, Roger] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ CORE, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 OCT PY 2011 VL 106 SU 2 MA 1149 BP S428 EP S428 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 885II UT WOS:000299772001711 ER PT J AU Alexander, KA Dovydaitis, T Beacham, B Bohinski, JM Brawner, BM Clements, CP Everett, JS Gomes, MM Harner, H McDonald, CC Pinkston, E Sommers, MS AF Alexander, Kamila A. Dovydaitis, Tiffany Beacham, Barbara Bohinski, Julia M. Brawner, Bridgette M. Clements, Carla P. Everett, Janine S. Gomes, Melissa M. Harner, Holly McDonald, Catherine C. Pinkston, Esther Sommers, Marilyn S. TI Learning Health Equity Frameworks within a Community of Scholars SO JOURNAL OF NURSING EDUCATION LA English DT Article AB Scholars in nursing science have long espoused the concept of health equity without specifically using the term or dialoguing about the social determinants of health and social justice. This article describes the development, implementation, and evaluation of a doctoral and postdoctoral seminar collective entitled "Health Equity: Conceptual, Linguistic, Methodological, and Ethical Issues." The course enabled scholars-in-training to consider the construct and its nuances and frame a personal philosophy of health equity. An example of how a group of emerging scholars can engage in the important, but difficult, discourse related to health equity is provided. The collective provided a forum for debate, intellectual growth, and increased insight for students and faculty. The lessons learned by all participants have the potential to enrich doctoral and postdoctoral scientific training in nursing science and may serve as a model for other research training programs in the health sciences. C1 [Alexander, Kamila A.; Dovydaitis, Tiffany; Beacham, Barbara; Bohinski, Julia M.; Brawner, Bridgette M.; Clements, Carla P.; Everett, Janine S.; McDonald, Catherine C.; Pinkston, Esther; Sommers, Marilyn S.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. [Harner, Holly] LaSalle Univ, MPH Program, Sch Nursing & Hlth Sci, Philadelphia, PA USA. [Gomes, Melissa M.] Virginia Commonwealth Univ, Sch Nursing, Richmond, VA USA. RP Alexander, KA (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, 418 Curie Blvd,Room 233L, Philadelphia, PA 19104 USA. EM kamilaa@nursing.upenn.edu FU National Institute of Nursing Research [T32NR007100, F31NR011524, 2R01NR005352, F31NR011106, F31NR011107]; University of Pennsylvania FX This work was supported by the Ruth L. Kirschstein NRSA Pre & Post doctoral Fellowship at the University of Pennsylvania School of Nursing, Research on Vulnerable Women, Children and Families T32NR007100 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 work was also supported by Award Number F31NR011524 (to Barbara Beacham) from the National Institute of Nursing Research; Offices of the Provost and School of Nursing Dean from the University of Pennsylvania (to Bridgette M. Brawner); Diversity Supplement to 2R01NR005352 (to Carla Clements) from the National Institute of Nursing Research; Award Number F31NR011106 (to Janine S. Everett) from the National Institute of Nursing Research; and Award Number F31NR011107 (to Catherine C. McDonald) from the National Institute of Nursing Research. NR 13 TC 2 Z9 2 U1 0 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0148-4834 J9 J NURS EDUC JI J. Nurs. Educ. PD OCT PY 2011 VL 50 IS 10 BP 569 EP 574 DI 10.3928/01484834-20110630-05 PG 6 WC Nursing SC Nursing GA 884VK UT WOS:000299736700005 PM 21710960 ER PT J AU Bailey, RR Stuckey, DR Norman, BA Duggan, AP Bacon, KM Connor, DL Lee, I Muder, RR Lee, BY AF Bailey, Rachel R. Stuckey, Dianna R. Norman, Bryan A. Duggan, Andrew P. Bacon, Kristina M. Connor, Diana L. Lee, Ingi Muder, Robert R. Lee, Bruce Y. TI Home-Based Preoperative Chlorhexidine Bathing Cloths to Prevent Surgical Site Infection Reply SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Letter C1 [Bailey, Rachel R.] Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR, Sect Decis Sci & Clin Syst Modeling, Pittsburgh, PA 15213 USA. [Bailey, Rachel R.; Stuckey, Dianna R.; Bacon, Kristina M.; Connor, Diana L.; Lee, Bruce Y.] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA 15213 USA. [Bailey, Rachel R.; Stuckey, Dianna R.; Bacon, Kristina M.; Connor, Diana L.; Lee, Bruce Y.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Norman, Bryan A.; Duggan, Andrew P.] Univ Pittsburgh, Dept Ind Engn, Pittsburgh, PA 15213 USA. [Lee, Ingi] Univ Penn, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Lee, Ingi] Univ Penn, Sch Med, Ctr Evidence Based Practice, Philadelphia, PA 19104 USA. [Muder, Robert R.] Vet Affairs Pittsburgh Healthcare Syst, Div Infect Dis, Pittsburgh, PA USA. RP Bailey, RR (reprint author), Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR, Sect Decis Sci & Clin Syst Modeling, 3520 Forbes Ave,1st Floor, Pittsburgh, PA 15213 USA. EM RRB16@pitt.edu NR 6 TC 0 Z9 0 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD OCT PY 2011 VL 32 IS 10 BP 1047 EP 1048 DI 10.1086/662024 PG 2 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 876BX UT WOS:000299083100016 ER PT J AU Folmer, RL Billings, CJ Diedesch-Rouse, AC Gallun, FJ Lew, HL AF Folmer, Robert L. Billings, Curtis J. Diedesch-Rouse, Anna C. Gallun, Frederick J. Lew, Henry L. TI Electrophysiological assessments of cognition and sensory processing in TBI: Applications for diagnosis, prognosis and rehabilitation SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Review DE Event-related potentials; Evoked potentials; EP; ERP; TBI; Traumatic brain injury ID TRAUMATIC BRAIN-INJURY; EVENT-RELATED POTENTIALS; SOMATOSENSORY-EVOKED POTENTIALS; CLOSED-HEAD-INJURY; CONTINGENT NEGATIVE VARIATION; TEMPORAL-PARIETAL LESIONS; AUDITORY ODDBALL TASK; SUBJECTS OWN NAME; MISMATCH NEGATIVITY; COMATOSE PATIENTS AB Traumatic brain injuries are often associated with damage to sensory and cognitive processing pathways. Because evoked potentials (EPs) and event-related potentials (ERPs) are generated by neuronal activity, they are useful for assessing the integrity of neural processing capabilities in patients with traumatic brain injury (TBI). This review of somatosensory, auditory and visual ERPs in assessments of TBI patients is provided with the hope that it will be of interest to clinicians and researchers who conduct or interpret electrophysiological evaluations of this population. Because this article reviews ERP studies conducted in three different sensory modalities, involving patients with a wide range of TBI severity ratings and circumstances, it is difficult to provide a coherent summary of findings. However, some general trends emerge that give rise to the following observations and recommendations: 1) bilateral absence of somatosensory evoked potentials (SEPs) is often associated with poor clinical prognosis and outcome; 2) the presence of normal ERPs does not guarantee favorable outcome; 3) ERPs evoked by a variety of sensory stimuli should be used to evaluate TBI patients, especially those with severe injuries; 4) time since onset of injury should be taken into account when conducting ERP evaluations of TBI patients or interpreting results; 5) because sensory deficits (e.g., vision impairment or hearing loss) affect ERP results, tests of peripheral sensory integrity should be conducted in conjunction with ERP recordings; and 6) patients' state of consciousness, physical and cognitive abilities to respond and follow directions should be considered when conducting or interpreting ERP evaluations. Published by Elsevier B.V. C1 [Folmer, Robert L.; Billings, Curtis J.; Diedesch-Rouse, Anna C.; Gallun, Frederick J.] Portland VA Med Ctr, NCRAR, Portland, OR 97239 USA. [Folmer, Robert L.; Billings, Curtis J.; Gallun, Frederick J.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. [Lew, Henry L.] DVBIC, Rockville, MD USA. [Lew, Henry L.] VCU, Sch Med, Dept Phys Med & Rehabil, Richmond, VA USA. RP Folmer, RL (reprint author), Portland VA Med Ctr, NCRAR, 3710 SM US Vet Hosp Rd, Portland, OR 97239 USA. EM Robert.Folmer@va.gov RI Gallun, Frederick/G-3792-2012 OI Gallun, Frederick/0000-0002-4145-2199 FU VA RR&D National Center for Rehabilitative Auditory Research FX Preparation of this manuscript was supported by the VA RR&D National Center for Rehabilitative Auditory Research, located in the Portland VA Medical Center, Portland, Oregon. NR 93 TC 18 Z9 18 U1 1 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD OCT PY 2011 VL 82 IS 1 SI SI BP 4 EP 15 DI 10.1016/j.ijpsycho.2011.03.005 PG 12 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 859PZ UT WOS:000297889600002 PM 21419179 ER PT J AU Woods, DL Phillips, LR Martin, JL AF Woods, Diana Lynn Phillips, Linda R. Martin, Jennifer L. TI Biological Basis for Sleep Disturbance and Behavioral Symptoms in Dementia A Biobehavioral Model SO RESEARCH IN GERONTOLOGICAL NURSING LA English DT Article ID NURSING-HOME RESIDENTS; MILD COGNITIVE IMPAIRMENT; APOLIPOPROTEIN-E GENOTYPE; CORTISOL SECRETORY ACTIVITY; PITUITARY-ADRENAL AXIS; LONG-TERM-CARE; ALZHEIMERS-DISEASE; SALIVARY CORTISOL; PSYCHOLOGICAL SYMPTOMS; APOE GENOTYPE AB Behavioral symptoms and sleep disturbance occur in more than 56% of older adults with mild to moderate dementia and are challenging and costly. This article proposes a biobehavioral causal model to explain sleep disturbances and behavioral symptoms in dementia (BSD) based on an integrative science perspective using the life cycle model of stress (chronic stress) integrating genetic, neuroendocrine, and personality factors. The model proposes that: (a) BSD are an outcome of sleep disturbance; (b) hypothalamic-pituitary-adrenal (HPA) axis dysregulation is key to sleep disturbances and BSD; (c) genotype influences response to stress hormones; (d) HPA is influenced by genotype; (e) trait anxiety moderates the relationship between HPA axis and BSD and/or sleep disturbances; and (f) trait anxiety is influenced by genotype. Examining these relationships simultaneously will advance our theoretical understanding of BSD and sleep disturbances, potentially providing a basis for the design of targeted interventions and prevention strategies with an understanding of risk. C1 [Woods, Diana Lynn; Phillips, Linda R.] Univ Calif Los Angeles, Sch Nursing, Ctr Adv Gerontol Nursing Sci, Los Angeles, CA 90095 USA. [Martin, Jennifer L.] Univ Calif Los Angeles, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90095 USA. [Martin, Jennifer L.] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. RP Woods, DL (reprint author), Univ Calif Los Angeles, Sch Nursing, Ctr Adv Gerontol Nursing Sci, 700 Tiverton Ave,Box 956919, Los Angeles, CA 90095 USA. EM lwoods@sonnet.ucla.edu FU University of California, Los Angeles, School of Nursing; National Institute on Aging [K23 AG028452] FX The authors disclose that they have no significant financial interests in any product or class of products discussed directly or indirectly in this activity. The authors acknowledge pilot study support from the University of California, Los Angeles, School of Nursing, Intramural Grant (D. L. Woods) and National Institute on Aging grant K23 AG028452 (L.R. Phillips). NR 125 TC 3 Z9 3 U1 3 U2 8 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1940-4921 J9 RES GERONTOL NURS JI Res. Gerontol. Nurs. PD OCT PY 2011 VL 4 IS 4 BP 281 EP 293 DI 10.3928/19404921-20110302-01 PG 13 WC Nursing SC Nursing GA 864YL UT WOS:000298276300007 PM 21417189 ER PT J AU Kehinde, JO Pope, C Amella, EJ AF Kehinde, Julius Oluwole Pope, Charlene Amella, Elaine J. TI Methodological Issues in Fall Prevention Research Involving Older Adults in Long-Term Care Facilities SO RESEARCH IN GERONTOLOGICAL NURSING LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; NURSING-HOME RESIDENTS; RISK ASSESSMENT-TOOL; TAI-CHI; STRATEGIES; PEOPLE; COSTS; INTERVENTION; PROGRAMS; CLUSTER AB The purpose of this study was to conduct a systematic review of the current fall prevention literature, examining methodological issues resulting from variations in fall definitions, methods of data collection, and standards for reporting fall rates in studies involving older adults in long-term care settings. This systematic review used the five stages of Whittemore and Knafl's review methodology to extract data from the databases, summarize, and synthesize the findings of the 10 studies included. The Critical Appraisal Skill Program checklist for randomized controlled trials criteria was used to appraise the methodological quality of the studies. Inconsistencies in fall definitions, methods of data collection, and standards for reporting fall rates were apparent across the studies reviewed. Standardized approaches to defining falls, collecting data, and reporting fall rates are necessary to interpret, make comparisons among, and disseminate the findings of studies. C1 [Kehinde, Julius Oluwole; Pope, Charlene; Amella, Elaine J.] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. [Pope, Charlene] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Kehinde, JO (reprint author), Med Univ S Carolina, Coll Nursing, 99 Jonathan Lucas St, Charleston, SC 29425 USA. EM jok31@musc.edu OI Amella, Elaine/0000-0003-4114-429X NR 56 TC 1 Z9 1 U1 3 U2 14 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1940-4921 J9 RES GERONTOL NURS JI Res. Gerontol. Nurs. PD OCT PY 2011 VL 4 IS 4 BP 294 EP 304 DI 10.3928/19404921-20110503-02 PG 11 WC Nursing SC Nursing GA 864YL UT WOS:000298276300008 PM 21598864 ER PT J AU Siek, KA Khan, DU Ross, SE Haverhals, LM Meyers, J Cali, SR AF Siek, Katie A. Khan, Danish U. Ross, Stephen E. Haverhals, Leah M. Meyers, Jane Cali, Steven R. TI Designing a Personal Health Application for Older Adults to Manage Medications: A Comprehensive Case Study SO JOURNAL OF MEDICAL SYSTEMS LA English DT Article DE Older adults; Personal Health Records; Personal Health Applications; Participatory design; Medication management; Interdisciplinary design ID NONADHERENCE; CARE; HOSPITALIZATION; ADHERENCE; DISEASE; HOME AB Older adults with multiple chronic conditions often go through care transitions where they move between care facilities or providers during their treatment. These transitions are often uncoordinated and can imperil patients by omitted, duplicative, or contradictory care plans. Older adults sometimes feel overwhelmed with the new responsibility of coordinating the care plan with providers and changing their medication regimes. In response, we developed a Lesser General Public License (LGPL) open source, web-based Personal Health Application (PHA) using an iterative participatory design process that provided older adults and their caregivers the ability to manage their personal health information. In this paper, we document the PHA design process from low-fidelity prototypes to high-fidelity prototypes over the course of six user studies. Our findings establish the imperative need for interdisciplinary research and collaboration among all stakeholders to create effective PHAs. We conclude with design guidelines that encourage researchers to gradually increase functionality as users become more proficient. C1 [Siek, Katie A.; Khan, Danish U.; Meyers, Jane] Univ Colorado Boulder, Dept Comp Sci, Boulder, CO 80309 USA. [Ross, Stephen E.] Univ Colorado Denver, Div Gen Internal Med, Denver, CO 80202 USA. [Haverhals, Leah M.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. [Cali, Steven R.] Univ Colorado Denver, Denver, CO 80217 USA. RP Siek, KA (reprint author), Univ Colorado Boulder, Dept Comp Sci, 430 UCB, Boulder, CO 80309 USA. EM ksiek@cs.colorado.edu; khand@colorado.edu; Steve.Ross@ucdenver.edu; leah.haverhals@gmail.com; meyersjk@colorado.edu; stevecali@gmail.com FU Robert Wood Johnson Foundation [RWJ59880] FX We thank our participants and expert review panel for their valuable feedback. We also thank the reviewers for their insightful and constructive comments. This research was funded by the Robert Wood Johnson Foundation Project HealthDesign Grant RWJ59880 (PI Stephen E. Ross). NR 41 TC 23 Z9 23 U1 5 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0148-5598 J9 J MED SYST JI J. Med. Syst. PD OCT PY 2011 VL 35 IS 5 SI SI BP 1099 EP 1121 DI 10.1007/s10916-011-9719-9 PG 23 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 859DZ UT WOS:000297856600040 PM 21562730 ER PT J AU Horga, G Bernacer, J Dusi, N Entis, J Chu, KW Hazlett, EA Haznedar, MM Kemether, E Byne, W Buchsbaum, MS AF Horga, Guillermo Bernacer, Javier Dusi, Nicola Entis, Jonathan Chu, Kingwai Hazlett, Erin A. Haznedar, M. Mehmet Kemether, Eileen Byne, William Buchsbaum, Monte S. TI Correlations between ventricular enlargement and gray and white matter volumes of cortex, thalamus, striatum, and internal capsule in schizophrenia SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE Cerebral spinal fluid; Sulcal enlargement; Myelin; Fronto-thalamic connectivity ID SCHIZOTYPAL PERSONALITY-DISORDER; CORTICAL BRODMANNS AREAS; GLUCOSE METABOLIC-RATE; COMPREHENSIVE ASSESSMENT; HEALTHY-INDIVIDUALS; BRAIN; SIZE; MEDIODORSAL; PULVINAR; ABNORMALITIES AB Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI (patients with schizophrenia (n = 64) and healthy controls (n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule. C1 [Buchsbaum, Monte S.] Univ Calif San Diego, Dept Psychiat, NeuroPET Ctr, San Diego, CA 92121 USA. [Buchsbaum, Monte S.] Univ Calif San Diego, Dept Radiol, NeuroPET Ctr, San Diego, CA 92121 USA. [Horga, Guillermo; Entis, Jonathan; Chu, Kingwai; Kemether, Eileen] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Horga, Guillermo] Hosp Clin Barcelona, Dept Psychiat, Schizophrenia Clin Program, E-08036 Barcelona, Spain. [Bernacer, Javier] Univ Navarra, Clin Univ, Lab Funct Neuromorphol, Pamplona 31008, Spain. [Dusi, Nicola] Univ Verona, Policlin Giambattista Rossi, Dept Publ Hlth & Community Med, Sect Psychiat & Clin Psychol, I-37134 Verona, Italy. [Hazlett, Erin A.; Haznedar, M. Mehmet; Byne, William] James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. RP Buchsbaum, MS (reprint author), Univ Calif San Diego, Dept Psychiat, NeuroPET Ctr, 11388 Sorrento Valley Rd,Suite 100, San Diego, CA 92121 USA. EM mbuchsbaum@ucsd.edu RI Bernacer, Javier/P-5810-2014; Horga, Guillermo/M-8036-2016 OI Bernacer, Javier/0000-0002-4341-9763; Horga, Guillermo/0000-0002-9049-9786 NR 47 TC 17 Z9 18 U1 0 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD OCT PY 2011 VL 261 IS 7 BP 467 EP 476 DI 10.1007/s00406-011-0202-x PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 856EH UT WOS:000297619700003 PM 21431919 ER PT J AU Wang, Q Grozdanic, SD Harper, MM Hamouche, N Kecova, H Lazic, T Yu, CX AF Wang, Qi Grozdanic, Sinisa D. Harper, Matthew M. Hamouche, Nicolas Kecova, Helga Lazic, Tatjana Yu, Chenxu TI Exploring Raman spectroscopy for the evaluation of glaucomatous retinal changes SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE glaucoma; raman spectroscopy; retinal ganglion cells; detection; support vector machine ID FLUORESCENCE; MICROSCOPY; SPECTRA; MODELS; EYE AB Glaucoma is a chronic neurodegenerative disease characterized by apoptosis of retinal ganglion cells and subsequent loss of visual function. Early detection of glaucoma is critical for the prevention of permanent structural damage and irreversible vision loss. Raman spectroscopy is a technique that provides rapid biochemical characterization of tissues in a nondestructive and noninvasive fashion. In this study, we explored the potential of using Raman spectroscopy for detection of glaucomatous changes in vitro. Raman spectroscopic imaging was conducted on retinal tissues of dogs with hereditary glaucoma and healthy control dogs. The Raman spectra were subjected to multivariate discriminant analysis with a support vector machine algorithm, and a classification model was developed to differentiate disease tissues versus healthy tissues. Spectroscopic analysis of 105 retinal ganglion cells (RGCs) from glaucomatous dogs and 267 RGCs from healthy dogs revealed spectroscopic markers that differentiated glaucomatous specimens from healthy controls. Furthermore, the multivariate discriminant model differentiated healthy samples and glaucomatous samples with good accuracy [healthy 89.5% and glaucomatous 97.6% for the same breed (Basset Hounds); and healthy 85.0% and glaucomatous 85.5% for different breeds (Beagles versus Basset Hounds)]. Raman spectroscopic screening can be used for in vitro detection of glaucomatous changes in retinal tissue with a high specificity. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3642010] C1 [Wang, Qi; Yu, Chenxu] Iowa State Univ, Dept Agr & Biosyst Engn, Ames, IA 50011 USA. [Grozdanic, Sinisa D.; Harper, Matthew M.; Kecova, Helga; Lazic, Tatjana] US Dept Vet Affairs, Ctr Prevent & Treatment Visual Loss, Iowa City, IA 52246 USA. [Hamouche, Nicolas] McFarland Clin Eye Ctr, Ames, IA 50011 USA. RP Yu, CX (reprint author), Iowa State Univ, Dept Agr & Biosyst Engn, 3224 NSRIC, Ames, IA 50011 USA. EM chenxuyu@iastate.edu FU U.S. Department of Veterans Affairs Center for Prevention and Treatment of Visual Loss FX This study has been supported by the U.S. Department of Veterans Affairs Center for Prevention and Treatment of Visual Loss. NR 31 TC 3 Z9 3 U1 0 U2 8 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD OCT PY 2011 VL 16 IS 10 AR 107006 DI 10.1117/1.3642010 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 853ZV UT WOS:000297465200028 PM 22029368 ER PT J AU Basher, F Bunni, M Amani, Z Zhang, X Nowling, TK AF Basher, Fahmin Bunni, Marlene Amani, Zainab Zhang, Xian Nowling, Tamara K. TI Effects of Altering Fli1 Levels in Lupus T Cells on Disease Expression and T Cell Function in the MRL/Lpr Mouse Model. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Basher, Fahmin; Bunni, Marlene; Amani, Zainab; Zhang, Xian; Nowling, Tamara K.] Med Univ S Carolina, Charleston, SC 29425 USA. [Zhang, Xian; Nowling, Tamara K.] Ralph H Johnson VA Med Ctr, Charleston, SC 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2363 BP S921 EP S921 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621502749 ER PT J AU Brown, AG Hirsch, R Laor, T Francis, KA Hannon, MJ Kwoh, CK AF Brown, Amanda G. Hirsch, Raphael Laor, Tal Francis, Kimberly A. Hannon, Michael J. Kwoh, C. Kent TI Patients with Juvenile Idiopathic Arthritis and Rheumatoid Arthritis in "Physician Determined Clinical Remission" Have Evidence of Persistent Inflammation Revealed by 3T MRI SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Brown, Amanda G.; Hirsch, Raphael; Francis, Kimberly A.] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA. [Laor, Tal] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Laor, Tal] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Hannon, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare, Ctr Hlth Equity Res & Promot, 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 958 BP S376 EP S376 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621501153 ER PT J AU Chang, AY Ghazi, E Okawa, J Werth, VP AF Chang, Aileen Y. Ghazi, Elizabeth Okawa, Joyce Werth, Victoria P. TI Disease Activity and Quality of Life in Refractory Cutaneous Lupus Erythematosus Patients Initiated on Immunosuppressive Therapy SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Chang, Aileen Y.; Okawa, Joyce; Werth, Victoria P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Chang, Aileen Y.; Okawa, Joyce; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Ghazi, Elizabeth] UMDNJ Robert Wood Johnson Med Sch, Piscataway, NJ 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 617 BP S239 EP S239 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500613 ER PT J AU Chung, SA Brown, EE Williams, AH Bhangale, T Ramos, PS Ziegler, JT Freedman, BI Kimberly, RP Vyse, TJ Gregersen, PK Jacob, CO Alarcon-Riquelme, ME Tsao, BP Harley, JB Behrens, TW Petri, M Kamboh, MI Demirci, FY Manzi, S Criswell, LA Moser, KL Gaffney, PM Graham, RR Langefeld, CD AF Chung, Sharon A. Brown, Elizabeth E. Williams, Adrienne H. Bhangale, Tushar Ramos, Paula S. Ziegler, Julie T. Freedman, Barry I. Kimberly, Robert P. Vyse, Timothy J. Gregersen, Peter K. Jacob, Chaim O. Alarcon-Riquelme, Marta E. Tsao, Betty P. Harley, John B. Behrens, Timothy W. Petri, M. Kamboh, M. Ilyas Demirci, F. Yesim Manzi, Susan Criswell, Lindsey A. Moser, Kathy L. Gaffney, Patrick M. Graham, Robert R. Langefeld, Carl D. TI Lupus Nephritis Susceptibility Markers in PDGRFA-GSX2, SLC5A11, ID4, and HAS2-SNTB1 Regions Identified From a Meta-Analysis of Genome Wide Association Studies of Women with Systemic Lupus Erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Chung, Sharon A.; Criswell, Lindsey A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Brown, Elizabeth E.; Kimberly, Robert P.] Univ Alabama, Birmingham, AL USA. [Williams, Adrienne H.; Ramos, Paula S.; Ziegler, Julie T.; Freedman, Barry I.; Langefeld, Carl D.] Wake Forest Sch Med, Winston Salem, NC USA. [Bhangale, Tushar; Behrens, Timothy W.; Graham, Robert R.] Genentech Inc, San Francisco, CA 94080 USA. [Vyse, Timothy J.] Kings Coll London, London WC2R 2LS, England. [Gregersen, Peter K.] Feinstein Inst Med Res, Manhasset, NY USA. [Jacob, Chaim O.] Univ So Calif, Los Angeles, CA USA. [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta de Andalucia, Oklahoma Med Res Fdn, Ctr Genom & Oncol Res, Oklahoma City, OK 73104 USA. [Tsao, Betty P.] Univ Calif Los Angeles, Los Angeles, CA USA. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Harley, John B.] Med Ctr, US Dept Vet Affairs, Cincinnati, OH USA. [Petri, M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Kamboh, M. Ilyas; Demirci, F. Yesim] Univ Pittsburgh, Pittsburgh, PA USA. [Manzi, Susan] Allegheny Singer Res Inst, Pittsburgh, PA 15212 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2479 BP S967 EP S967 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621503050 ER PT J AU Davis, LA Pointer, LM Wolff, RK Reimold, AM Kerr, GS Mikuls, TR Cannon, GW Caplan, L AF Davis, Lisa A. Pointer, Lauren M. Wolff, Roger K. Reimold, Andreas M. Kerr, Gail S. Mikuls, Ted R. Cannon, Grant W. Caplan, Liron TI Association of Medicaons and Rheumatoid Arthritis Susceptibility Polymorphism with Lipid Profiles in Patients with Rheumatoid Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Davis, Lisa A.] Univ Colorado, Sch Med, Aurora, CO USA. [Pointer, Lauren M.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Wolff, Roger K.] Univ Utah, Salt Lake City, UT USA. [Reimold, Andreas M.] Univ Texas SW, Dallas, TX USA. [Kerr, Gail S.] Washington DC VA, Washington, DC USA. [Kerr, Gail S.] Georgetown Univ, Washington, DC USA. [Wolff, Roger K.] Dallas VA, Dallas, TX USA. [Mikuls, Ted R.] Omaha VA, Omaha, NE USA. [Mikuls, Ted R.] Univ Nebraska, Omaha, NE 68182 USA. [Cannon, Grant W.] Salt Lake City VA, Salt Lake City, UT USA. [Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. [Caplan, Liron] Denver VA, Aurora, CO 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 1181 BP S460 EP S461 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621501375 ER PT J AU Deng, Y Zhao, J Tan, W Kaufman, KM Brown, EE Edberg, JC Kamen, DL Gilkeson, GS Jacob, CO Scofield, RH Kimberly, RP Langefeld, CD Alarcon-Riquelme, ME Harley, JB Vyse, TJ Gaffney, PM Moser, KL James, JA Chen, JY Mikuls, TR Shadick, NA Weinblatt, ME Bridges, SL Paulus, HE Tsao, BP AF Deng, Yun Zhao, Jian Tan, Wenfeng Kaufman, Kenneth M. Brown, Elizabeth E. Edberg, Jeffrey C. Kamen, Diane L. Gilkeson, Gary S. Jacob, Chaim O. Scofield, Robert H. Kimberly, Robert P. Langefeld, Carl D. Alarcon-Riquelme, Marta E. Harley, John B. Vyse, Timothy J. Gaffney, Patrick M. Moser, Kathy L. James, Judith A. Chen, Ji-Yih Mikuls, Ted R. Shadick, Nancy A. Weinblatt, Michael E. Bridges, S. Louis, Jr. Paulus, Harold E. Tsao, Betty P. CA PROFILE Investigators BIOLUPUS GENLES TI Association of a Functional Variant in TLR7 with Systemic Lupus Erythematosus and Rheumatoid Arthritis in Multiple Ancestries SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Deng, Yun; Zhao, Jian; Tan, Wenfeng; Paulus, Harold E.; Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Kaufman, Kenneth M.; Scofield, Robert H.; Alarcon-Riquelme, Marta E.; Gaffney, Patrick M.; Moser, Kathy L.; BIOLUPUS GENLES] US Dept Vet Affairs, Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Med Ctr, Oklahoma City, OK USA. [Brown, Elizabeth E.; Edberg, Jeffrey C.; Kimberly, Robert P.; PROFILE Investigators] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Brown, Elizabeth E.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. [Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Scofield, Robert H.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta de Andalucia, Ctr Genom & Oncol Res, Granada, Spain. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Mol Med & Immunol, London WC2R 2LS, England. [Chen, Ji-Yih] Chang Gung Mem Hosp, Div Allergy Immunol & Rheumatol, Taipei 10591, Taiwan. [Mikuls, Ted R.] Omaha VA, Omaha, NE USA. [Mikuls, Ted R.] Univ Nebraska, Omaha, NE 68182 USA. [Shadick, Nancy A.; Weinblatt, Michael E.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Bridges, S. Louis, Jr.] Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. RI Zhao, Jian/E-6292-2012 NR 0 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 634 BP S246 EP S247 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500630 ER PT J AU Dillon, SP Kao, L Kaufman, KM Ice, JA Omdal, R Mariette, X Witte, T Illei, GG Rischmueller, M Nordmark, G Jonsson, R Herlenius, MW Vyse, TJ Brennan, MT Rybicki, BA Ng, WF Segal, BM Rhodus, NL Merrill, JT Montgomery, CG Lessard, CJ Harley, JB Moser, KL Gaffney, PM Scofield, RH AF Dillon, Skyler P. Kao, Lydia Kaufman, Kenneth M. Ice, John A. Omdal, Roald Mariette, Xavier Witte, Torsten Illei, Gabor G. Rischmueller, Maureen Nordmark, Gunnel Jonsson, Roland Herlenius, Marie Wahren Vyse, Timothy J. Brennan, Michael T. Rybicki, Benjamin A. Ng, Wan-Fai Segal, Barbara M. Rhodus, Nelson L. Merrill, Joan T. Montgomery, Courtney G. Lessard, Christopher J. Harley, John B. Moser, Kathy L. Gaffney, Patrick M. Scofield, R. Hal TI Triple X Syndrome (47,XXX) Increases the Risk and Accelerates the Onset of Systemic Lupus Erythematosus and Sjogren's Syndrome: Support for a Gene-Dose Effect From the X Chromosome SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Dillon, Skyler P.; Kao, Lydia] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Omdal, Roald] Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway. [Mariette, Xavier] Univ Paris 11, Le Kremlin Bicetre, France. [Witte, Torsten] Hannover Med Sch, Hannover, Germany. [Illei, Gabor G.] NIDCR, NIH, Bethesda, MD USA. [Rischmueller, Maureen] Queen Elizabeth Hosp, Adelaide, SA, Australia. [Nordmark, Gunnel] Uppsala Univ, Rheumatol Sect, Dept Med Sci, Uppsala, Sweden. [Herlenius, Marie Wahren] CMM L8204 Karolinska Hosp, Stockholm, Sweden. [Jonsson, Roland] Univ Bergen, Bergen, Norway. [Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Mol Med & Immunol, London WC2R 2LS, England. [Brennan, Michael T.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Rybicki, Benjamin A.] Henry Ford Hlth Syst, Detroit, MI USA. [Ng, Wan-Fai] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Segal, Barbara M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Rhodus, Nelson L.] Univ Minnesota, Minneapolis, MN USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Moser, Kathy L.; Gaffney, Patrick M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK USA. RI Witte, Torsten/B-5783-2016 NR 0 TC 2 Z9 2 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 OCT PY 2011 VL 63 IS 10 SU S MA 643 BP S251 EP S251 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500639 ER PT J AU Ding, YN Hsu, HC Mountz, JD AF Ding, Yanna Hsu, Hui-Chen Mountz, John D. TI Identification of a CD62L(hi)CD44(low) T-FH Precursor Capable of Developing into An IL21(hi) IL17(hi) Mature T-FH in Autoimmune BXD2 Mice. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Ding, Yanna; Hsu, Hui-Chen; Mountz, John D.] Univ Alabama, Birmingham, AL USA. [Mountz, John D.] Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2362 BP S920 EP S921 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621502748 ER PT J AU Domsic, RT Lucas, M Wisniewski, SR Kwoh, CK Fine, MJ Medsger, TA AF Domsic, Robyn T. Lucas, Mary Wisniewski, Stephen R. Kwoh, C. Kent Fine, Michael J. Medsger, Thomas A. TI Development and Internal Validation of a Two-Year Mortality Risk Prediction Rule in Early Diffuse Systemic Sclerosis Patients SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Domsic, Robyn T.; Lucas, Mary; Wisniewski, Stephen R.; Kwoh, C. Kent; Fine, Michael J.; Medsger, Thomas A.] Univ Pittsburgh, Pittsburgh, PA USA. [Kwoh, C. Kent; Fine, Michael J.] VA Pittsburgh Healthcare, Ctr Hlth Equ Res & Promot, 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2485 BP S969 EP S970 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621503056 ER PT J AU Galasso, JA AF Galasso, Janine A. TI What Is the Health Literacy and Numeracy in a Rheumatology Veterans Population? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Galasso, Janine A.] Philadelphia VA Med Ctr, Philadelphia, 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 1551 BP S606 EP S606 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621501745 ER PT J AU Ghazi, E Kling, MA Propert, K Okawa, J Werth, VP AF Ghazi, Elizabeth Kling, Mitchel A. Propert, Kathleen Okawa, Joyce Werth, Victoria P. TI Increased Depression and Anxiety Symptoms in a Group of Dermatomyositis Patients SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Ghazi, Elizabeth] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. [Kling, Mitchel A.; Okawa, Joyce; Werth, Victoria P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Okawa, Joyce; Werth, Victoria P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 249 BP S92 EP S92 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500249 ER PT J AU Hughes, T Adler, A Merrill, JT Kelly, JA Kaufman, K Williams, A Langefeld, CD Gilkeson, GS Sanchez, E Martin, J Gaffney, PM Moser, KL Vyse, TJ Alarcon-Riquelme, ME James, JA Scofield, RH Harley, JB Richardson, BC Sawalha, AH AF Hughes, Travis Adler, Adam Merrill, J. T. Kelly, Jennifer A. Kaufman, Kenneth Williams, Adrienne Langefeld, Carl D. Gilkeson, Gary S. Sanchez, Elena Martin, Javier Gaffney, Patrick M. Moser, Kathy L. Vyse, Tomothy J. Alarcon-Riquelme, Marta E. James, Judith A. Scofield, Robert H. Harley, John B. Richardson, Bruce C. Sawalha, Amr H. CA Elizabeth E Brown PROFILE TI Sex-Specific Genetic Architecture of Systemic Lupus Erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta de Andalucia, Oklahoma Med Res Fdn, Ctr Genom & Oncol Res, Oklahoma City, OK USA. [Williams, Adrienne] Wake Forest Univ, Winston Salem, NC 27109 USA. [Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Martin, Javier] Inst Parasitol & Biomed Lopez Neyra CSIC, Granada, Spain. [Elizabeth E Brown PROFILE] Univ Alabama, Birmingham, AL USA. [Vyse, Tomothy J.] Kings Coll London, Guys Hosp, London WC2R 2LS, England. [James, Judith A.; Scofield, Robert H.] Univ Oklahoma, Hlth Sci Ctr, US Dept Vet Affairs, Arthritis & Clin Immunol Res Program,Oklahoma Med, Oklahoma City, OK USA. [Scofield, Robert H.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Richardson, Bruce C.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 157 BP S57 EP S57 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500158 ER PT J AU Hwang, YG Lim, FC Wu, Q Yang, PA Fisher, G Hunter, G Hsu, HC Mountz, JD AF Hwang, Yong Gil Lim, Fei Chu Wu, Qi Yang, PingAr Fisher, Gordon Hunter, Gary Hsu, Hui-Chen Mountz, John D. TI A Novel Role for Vitamin D in Immunosenescence: Is Enough Too Much for Naive CD8 T Cells? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Fisher, Gordon] Univ Alabama, Dept Nutr Sci, Birmingham, AL USA. [Hunter, Gary] Univ Alabama, Dept Human Studies, Birmingham, AL USA. [Mountz, John D.] Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2348 BP S915 EP S916 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621502734 ER PT J AU Kariuki, S Franek, BS Kumar, AA Kumabe, M Kaufman, KM Anaya, JM Alarcon-Riquelme, ME Bae, SC Brown, EE Freedman, BI Gilkeson, GS Jacob, CO James, JA Kimberly, RP Martin, J Merrill, JT Pons-Estel, B Tsao, BP Vyse, TJ Langefeld, CD Harley, JB Moser, KL Gaffney, PM Skol, AD Niewold, TB AF Kariuki, Silvia Franek, Beverly S. Kumar, Akaash A. Kumabe, Marissa Kaufman, Kenneth M. Anaya, Juan-Manuel Alarcon-Riquelme, Marta E. Bae, Sang-Cheol Brown, Elizabeth E. Freedman, Barry I. Gilkeson, Gary S. Jacob, Chaim O. James, Judith A. Kimberly, Robert P. Martin, Javier Merrill, Joan T. Pons-Estel, Bernardo Tsao, Betty P. Vyse, Timothy J. Langefeld, Carl D. Harley, John B. Moser, Kathy L. Gaffney, Patrick M. Skol, Andrew D. Niewold, Timothy B. TI Genetic Associations with Serologic Autoimmunity in a Large Multi-Ancestral Systemic Lupus Erythematosus Cohort SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Kariuki, Silvia; Franek, Beverly S.; Kumar, Akaash A.; Kumabe, Marissa; Skol, Andrew D.; Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA. [Kaufman, Kenneth M.; Moser, Kathy L.; Gaffney, Patrick M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Kaufman, Kenneth M.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Anaya, Juan-Manuel] Univ Rosario, Corp Invest Biol, Bogota, Colombia. [Alarcon-Riquelme, Marta E.] Oklahoma Med Res Fdn, Granada, Spain. [Alarcon-Riquelme, Marta E.] Ctr Genom & Invest Oncol Pfizer Univ Granada Junt, Granada, Spain. [Alarcon-Riquelme, Marta E.] BIOLUPUS Network, Oklahoma City, OK USA. [Alarcon-Riquelme, Marta E.] GENLES Network, Oklahoma City, OK USA. [Bae, Sang-Cheol] Hanyang Univ, Hosp Rheumat Dis, CRCRA, Seoul 133791, South Korea. [Brown, Elizabeth E.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Brown, Elizabeth E.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. [Freedman, Barry I.; Langefeld, Carl D.] Wake Forest Sch Med, Winston Salem, NC USA. [Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [James, Judith A.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Martin, Javier] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada, Spain. [Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Mol Med & Immunol, London WC2R 2LS, England. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. RI Anaya, Juan-Manuel/J-1960-2016 OI Anaya, Juan-Manuel/0000-0002-6444-1249 NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 633 BP S246 EP S246 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500629 ER PT J AU Kaufman, KM Kelly, JA Hughes, T Adler, A Sanchez, E Ojwang, JO Langefeld, CD Ziegler, JT James, JA Brown, EE Kimberly, RP Edberg, JC Criswell, LA Chang, DM Gilkeson, GS Niewold, TB Bae, SC Alarcon-Riquelme, ME Jacob, CO Moser, KL Gaffney, PM Harley, JB Sawalha, AH Tsao, BP AF Kaufman, Kenneth M. Kelly, Jennifer A. Hughes, Travis Adler, Adam Sanchez, Elena Ojwang, Joshua O. Langefeld, Carl D. Ziegler, Julie T. James, Judith A. Brown, Elizabeth E. Kimberly, Robert P. Edberg, Jeffrey C. Criswell, Lindsey A. Chang, Deh-Ming Gilkeson, Gary S. Niewold, Timothy B. Bae, Sang-Cheol Alarcon-Riquelme, Marta E. Jacob, Chaim O. Moser, Kathy L. Gaffney, Patrick M. Harley, John B. Sawalha, Amr H. Tsao, Betty P. TI Fine Mapping of Xq28: Both MECP2/IRAK1 and NAA10/RENBP Contribute to Risk for SLE in Multiple Ancestral Groups SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Kaufman, Kenneth M.; Moser, Kathy L.; Gaffney, Patrick M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Kaufman, Kenneth M.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Langefeld, Carl D.; Ziegler, Julie T.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Brown, Elizabeth E.; Edberg, Jeffrey C.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Brown, Elizabeth E.] Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA. [Criswell, Lindsey A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Chang, Deh-Ming] Natl Def Med Ctr, Taipei, Taiwan. [Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA. [Bae, Sang-Cheol] Hanyang Univ, Hosp Rheumat Dis, CRCRA, Seoul 133791, South Korea. [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta de Andalucia GENYO, Ctr Genom & Invest Oncol, Granada, Spain. [Alarcon-Riquelme, Marta E.] BIOLUPUS Network, Oklahoma City, OK USA. [Alarcon-Riquelme, Marta E.] GENLES Network, Oklahoma City, OK USA. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Harley, John B.] Cincinnato Childrens Hosp Med Ctr, Cincinnati, OH USA. [Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 642 BP S250 EP S251 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500638 ER PT J AU Kwoh, CK Hannon, MJ Green, SM Guermazi, A Boudreau, RM AF Kwoh, C. Kent Hannon, Michael J. Green, Stephanie M. Guermazi, Ali Boudreau, Robert M. TI A Screening Tool for Knee Osteoarthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Hannon, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Guermazi, Ali] Boston Med Ctr, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2079 BP S810 EP S810 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621502465 ER PT J AU Kwoh, CK Guermazi, A Hannon, MJ Boudreau, RM Green, SM Jakicic, JM Roemer, F AF Kwoh, C. Kent Guermazi, Ali Hannon, Michael J. Boudreau, Robert M. Green, Stephanie M. Jakicic, John M. Roemer, Frank TI Identification of Magnetic Resonance Imaging Morphologic Features Associated with Different Knee Pain Patterns SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Hannon, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Guermazi, Ali] Boston Med Ctr, Boston, MA USA. [Roemer, Frank] Boston Univ, Boston, MA 02215 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 959 BP S376 EP S376 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621501154 ER PT J AU Lessard, CJ Adrianto, I Ice, JA Kelly, JA Li, H Wiley, GB Rasmussen, A Alarcon-Riquelme, ME Anaya, JM Bae, SC Brown, EE Jacob, CO James, JA Martin, J Niewold, TB Pons-Estel, B Tsao, BP Vyse, TJ Harley, JB Wakeland, E Kaufman, KM Montgomery, C Langefeld, CD Gaffney, PM Moser, KL AF Lessard, Christopher J. Adrianto, Indra Ice, John A. Kelly, Jennifer A. Li, He Wiley, Graham B. Rasmussen, Astrid Alarcon-Riquelme, Marta E. Anaya, Juan-Manuel Bae, Sang-Cheol Brown, Elizabeth E. Jacob, Chaim O. James, Judith A. Martin, Javier Niewold, Timothy B. Pons-Estel, Bernardo Tsao, Betty P. Vyse, Timothy J. Harley, John B. Wakeland, Edward Kaufman, Kenneth M. Montgomery, Courtney Langefeld, Carl D. Gaffney, Patrick M. Moser, Kathy L. TI A Large-Scale, Multi-Racial Replication Study Identifies Novel Systemic Lupus Erythematosus Susceptibility Loci At IRF8, TMEM39A, and IKZF3/ZPBP2 SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta Andalucia, Oklahoma Med Res Fdn, Ctr Genom & Oncol Res, Oklahoma City, OK USA. [Anaya, Juan-Manuel] Univ Rosario, Corp Invest Biol, Bogota, Colombia. [Bae, Sang-Cheol] Hanyang Univ, Hosp Rheumat Dis, CRCRA, Seoul 133791, South Korea. [Brown, Elizabeth E.] Univ Alabama, Birmingham, AL USA. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Martin, Javier] Inst Parasitol & Biomed Lopez Neyra CSIC, Granada, Spain. [Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA. [Tsao, Betty P.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Mol Med, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Immunol, London WC2R 2LS, England. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Harley, John B.] Med Ctr, US Dept Vet Affairs, Cincinnati, OH USA. [Wakeland, Edward] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Kaufman, Kenneth M.; Gaffney, Patrick M.; Moser, Kathy L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Kaufman, Kenneth M.] Med Ctr, US Dept Vet Affairs, Oklahoma City, OK USA. [Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. RI Adrianto, Indra/D-4214-2013; Anaya, Juan-Manuel/J-1960-2016 OI Adrianto, Indra/0000-0002-9973-3057; Anaya, Juan-Manuel/0000-0002-6444-1249 NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2475 BP S965 EP S965 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621503046 ER PT J AU Lessard, CJ Adrianto, I Ice, JA Kelly, JA Jonsson, R Illei, GG Rischmueller, M Nordmark, G Mariette, X Miceli-Richard, C Herlenius, MW Witte, T Brennan, MT Omdal, R Gaffney, PM Lessard, JA Ng, WF Rhodus, NL Segal, BM Scofield, RH James, JA Anaya, JM Harley, JB Montgomery, C Moser, KL AF Lessard, Christopher J. Adrianto, Indra Ice, John A. Kelly, Jennifer A. Jonsson, Roland Illei, Gabor G. Rischmueller, Maureen Nordmark, Gunnel Mariette, Xavier Miceli-Richard, Corinne Herlenius, Marie Wahren Witte, Torsten Brennan, Michael T. Omdal, Roald Gaffney, Patrick M. Lessard, James A. Ng, Wan-Fai Rhodus, Nelson L. Segal, Barbara M. Scofield, R. Hal James, Judith A. Anaya, Juan-Manuel Harley, John B. Montgomery, Courtney Moser, Kathy L. TI Large-Scale, High-Density Genotyping Performed by the Sjogren's Genetics Network Using the ImmunoChip Identifies PRKRA as a Novel Sjogren's Syndrome Susceptibility Locus and Confirms Associations with IRF5, BLK and MHC SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Gaffney, Patrick M.; Moser, Kathy L.] Oklahoma Med Res Fdn, Arthritis & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Jonsson, Roland] Univ Bergen, Bergen, Norway. [Illei, Gabor G.] NIDCR, NIH 10 1N110, Bethesda, MD USA. [Rischmueller, Maureen] Queen Elizabeth Hosp, Adelaide, SA, Australia. [Nordmark, Gunnel] Uppsala Univ, Rheumatol Sect, Dept Med Sci, Uppsala, Sweden. [Mariette, Xavier; Miceli-Richard, Corinne] Bicetre Univ Hosp, Le Kremlin Bicetre, France. [Herlenius, Marie Wahren] Karolinska Inst, Stockholm, Sweden. [Witte, Torsten] Hannover Med Sch, Hannover, Germany. [Brennan, Michael T.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Omdal, Roald] Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway. [Lessard, James A.] Valley Bone& Joint Clin, Grand Forks, ND USA. [Ng, Wan-Fai] Newcastle Univ, Inst Cellular Med, Musculoskeletal Res Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Rhodus, Nelson L.] Univ Minnesota, Minneapolis, MN USA. [Segal, Barbara M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Anaya, Juan-Manuel] Univ Rosario Corp Invest Biol, Bogota, Colombia. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. RI Adrianto, Indra/D-4214-2013; Witte, Torsten/B-5783-2016; Anaya, Juan-Manuel/J-1960-2016 OI Adrianto, Indra/0000-0002-9973-3057; Anaya, Juan-Manuel/0000-0002-6444-1249 NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 773 BP S303 EP S304 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500769 ER PT J AU Lessard, CJ Ice, JA Adrianto, I Kelly, JA Jonsson, R Illei, GG Rischmueller, M Nordmark, G Mariette, X Miceli-Richard, C Herlenius, MW Witte, T Brennan, MT Omdal, R Vyse, TJ Lessard, JA Ng, WF Rhodus, NL Segal, BM Scofield, RH Anaya, JM Harley, JB Montgomery, CG Moser, KL AF Lessard, Christopher J. Ice, John A. Adrianto, Indra Kelly, Jennifer A. Jonsson, Roland Illei, Gabor G. Rischmueller, Maureen Nordmark, Gunnel Mariette, Xavier Miceli-Richard, Corinne Herlenius, Marie Wahren Witte, Torsten Brennan, Michael T. Omdal, Roald Vyse, Timothy J. Lessard, James A. Ng, Wan-Fai Rhodus, Nelson L. Segal, Barbara M. Scofield, R. Hal Anaya, Juan-Manuel Harley, John B. Montgomery, Courtney G. Moser, Kathy L. CA Benjamin A Rybicki ACCESS TI A High-Density Genome-Wide Association Study by the Sjogren's Genetics Network Identifies Five Novel Susceptibility Loci for Primary Sjogren's Syndrome and Confirms Association with MHC, IRF5, and BLK SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Lessard, Christopher J.; Ice, John A.; Adrianto, Indra; Kelly, Jennifer A.; Scofield, R. Hal; Montgomery, Courtney G.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Jonsson, Roland] Univ Bergen, Bergen, Norway. [Illei, Gabor G.] NIDCR, NIH, Bethesda, MD USA. [Rischmueller, Maureen] Queen Elizabeth Hosp, Adelaide, SA, Australia. [Nordmark, Gunnel] Uppsala Univ, Rheumatol Sect, Dept Med Sci, Uppsala, Sweden. [Mariette, Xavier; Miceli-Richard, Corinne] Bicetre Univ Hosp, Le Kremlin Bicetre, France. [Herlenius, Marie Wahren] Karolinska Inst, Stockholm, Sweden. [Witte, Torsten] Hannover Med Sch, D-3000 Hannover, Germany. [Brennan, Michael T.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Omdal, Roald] Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway. [Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Mol Med & Immunol, London WC2R 2LS, England. [Lessard, James A.] Valley Bone & Joint Clin, Grand Forks, ND USA. [Ng, Wan-Fai] Newcastle Univ, Inst Cellular Med, Musculoskeletal Res Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Rhodus, Nelson L.] Univ Minnesota, Minneapolis, MN USA. [Segal, Barbara M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Benjamin A Rybicki ACCESS] Henry Ford Hosp, Detroit, MI 48202 USA. [Anaya, Juan-Manuel] Univ Rosario Corp Invest Biol, Bogota, Colombia. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Moser, Kathy L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. RI Adrianto, Indra/D-4214-2013; Witte, Torsten/B-5783-2016; Anaya, Juan-Manuel/J-1960-2016 OI Adrianto, Indra/0000-0002-9973-3057; Anaya, Juan-Manuel/0000-0002-6444-1249 NR 0 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 481 BP S184 EP S184 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500481 ER PT J AU Li, H Hsu, HC Li, J Wu, Q Yang, PA Cua, D Mountz, JD AF Li, Hao Hsu, Hui-Chen Li, Jun Wu, Qi Yang, PingAr Cua, Daniel Mountz, John D. TI IL-23 Upregulates IRF5 and Polarizes Inflammatory M1 Macrophages to Promote Inflammation in a Mouse Model of Arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Li, Hao; Hsu, Hui-Chen; Li, Jun; Wu, Qi; Yang, PingAr; Mountz, John D.] Univ Alabama, Birmingham, AL USA. [Cua, Daniel] Merck Res Lab, Palo Alto, CA USA. [Mountz, John D.] Birmingham VAMC, Birmingham, AL 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2097 BP S816 EP S817 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621502483 ER PT J AU Li, J Hsu, HC Yang, P Wu, Q Mountz, JD AF Li, Jun Hsu, Hui-Chen Yang, PingAr Wu, Qi Mountz, John D. TI Fucosylation Inhibitor, 2-D-Gal, Promotes Human Synovial Fibroblast Apoptosis and Is a Potent Suppressor of Arthritis in a TNF-alpha Tg Mouse Model In Vivo SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Li, Jun; Hsu, Hui-Chen; Yang, PingAr; Wu, Qi; Mountz, John D.] Univ Alabama, Birmingham, AL USA. [Mountz, John D.] Birmingham VAMC, Birmingham, AL 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2248 BP S879 EP S880 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621502634 ER PT J AU Li, J Hsu, HC Yang, P Wu, Q Li, H Mountz, JD AF Li, Jun Hsu, Hui-Chen Yang, PingAr Wu, Qi Li, Hao Mountz, John D. TI Rebalancing the IL-23/Th17 Axis and Regulatory T Cells in Arthritis by Depleting IRF5(+) IL-23(+) M1 Macrophages Using An Anti-Human DR5 Antibody SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Li, Jun; Hsu, Hui-Chen; Yang, PingAr; Wu, Qi; Li, Hao; Mountz, John D.] Univ Alabama, Birmingham, AL USA. [Mountz, John D.] Birmingham VAMC, Birmingham, AL 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2246 BP S878 EP S879 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621502632 ER PT J AU Maxwell, JL Felson, DT Niu, JB Wise, B Nevitt, MC Singh, J Frey-Law, L Neogi, T AF Maxwell, Jessica L. Felson, David T. Niu, Jingbo Wise, Barton Nevitt, Michael C. Singh, Jasvinder Frey-Law, Laura Neogi, Tuhina TI Does Important Improvement in Function After Knee Replacement Guarantee Good Absolute Function SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Felson, David T.; Niu, Jingbo; Neogi, Tuhina] Boston Univ, Sch Med, Boston, MA 02118 USA. [Wise, Barton] Ctr Hlth Aging UC Davis, Sacramento, CA USA. [Nevitt, Michael C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Singh, Jasvinder] Univ Alabama, Birmingham, AL USA. [Singh, Jasvinder] Birmingham VA Med Ctr, Birmingham, AL USA. [Frey-Law, Laura] Univ Iowa, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 7 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 OCT PY 2011 VL 63 IS 10 SU S MA 1541 BP S602 EP S602 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621501735 ER PT J AU Mohan, N Hannon, MJ Kwoh, CK AF Mohan, Niveditha Hannon, Michael J. Kwoh, C. Kent TI Correlation of Bony Enlargements with Radiological Findings in Hand Osteoarthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Mohan, Niveditha] Univ Pittsburgh, Arth Inst, Pittsburgh, PA USA. [Hannon, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare, Ctr Hlth Equity Res & Promot, 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 962 BP S377 EP S377 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621501157 ER PT J AU Mohan, N Hannon, MJ Kwoh, CK AF Mohan, Niveditha Hannon, Michael J. Kwoh, C. Kent TI Correlation of Hand Pain and Radiological Findings in Hand Osteoarthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Mohan, Niveditha] Univ Pittsburgh, Arth Inst, Pittsburgh, PA USA. [Hannon, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare, Ctr Hlth Equity Res & Promot, 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 963 BP S377 EP S378 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621501158 ER PT J AU Munroe, ME Guthridge, JM Kamen, DL Norris, JM Moser, KL Niewold, TB Gilkeson, GS Karp, DR Weisman, MH Ishimori, ML Wallace, DJ Harley, JB James, JA AF Munroe, Melissa E. Guthridge, Joel M. Kamen, Diane L. Norris, Jill M. Moser, Kathy L. Niewold, Timothy B. Gilkeson, Gary S. Karp, David R. Weisman, Michael H. Ishimori, Mariko L. Wallace, Daniel J. Harley, John B. James, Judith A. TI Altered Soluble Mediators of Inflammation At Baseline in Individuals Who Subsequently Transition to Systemic Lupus Erythematosus: Early Studies From the Lupus Autoimmunity in Relatives (LAUREL) Study SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Munroe, Melissa E.; Guthridge, Joel M.; Moser, Kathy L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Kamen, Diane L.] Med Univ SC, Charleston, SC USA. [Norris, Jill M.] Univ Colorado Denver, Aurora, CO USA. [Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA. [Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Karp, David R.] UT SW Med Ctr, Dallas, TX USA. [Weisman, Michael H.; Ishimori, Mariko L.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Wallace, Daniel J.] Cedars Sinai UCLA, Los Angeles, CA USA. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 1663 BP S650 EP S650 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621502049 ER PT J AU Neogi, T Niu, JB Felson, DT Nevitt, MC Zhang, YQ Frey-Law, L Maxwell, JL Singh, J AF Neogi, Tuhina Niu, Jingbo Felson, David T. Nevitt, Michael C. Zhang, Yuqing Frey-Law, Laura Maxwell, Jessica L. Singh, Jasvinder TI Time-Course and Extent of Pain and Function Improvements Post-Knee Replacement: The Multicenter Osteoarthritis Study SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Neogi, Tuhina; Niu, Jingbo; Felson, David T.; Zhang, Yuqing; Maxwell, Jessica L.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Nevitt, Michael C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Frey-Law, Laura] Univ Iowa, Iowa City, IA USA. [Singh, Jasvinder] Univ Alabama, Birmingham, AL USA. [Singh, Jasvinder] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 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 OCT PY 2011 VL 63 IS 10 SU S MA 742 BP S289 EP S289 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500738 ER PT J AU Pruhs, Z Michaud, KD Erickson, AR Sayles, H Kerr, GS Gaffo, AL Caplan, L Cannon, GW Lazaro, DM Reimold, AM Johnson, DS Cherascu, B Schwab, P Khan, NA Mikuls, TR AF Pruhs, Zachary Michaud, Kaleb D. Erickson, Alan R. Sayles, Harlan Kerr, Gail S. Gaffo, Angelo L. Caplan, Liron Cannon, Grant W. Lazaro, Deana M. Reimold, Andreas M. Johnson, Dannette S. Cherascu, Bogdan Schwab, Pascale Khan, Nasim A. Mikuls, Ted R. TI Vascular Calcification On Hand and Wrist Radiographs Are Associated with Comorbidity and Overall Mortality In Rheumatoid Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Pruhs, Zachary; Michaud, Kaleb D.] Univ Nebraska Med Ctr, Omaha, NE USA. [Michaud, Kaleb D.] Natl Data Bank Rheumat Dis, Omaha, NE USA. [Erickson, Alan R.] UNMC Phys Brentwood, Lavista, NE USA. [Sayles, Harlan] Univ Nebraska, Sch Med, Omaha, NE 68198 USA. [Kerr, Gail S.] Washington DC VA, Washington, DC USA. [Kerr, Gail S.] Georgetown Univ, Washington, DC USA. [Gaffo, Angelo L.] Birmingham VA Med Ctr, Birmingham, AL USA. [Caplan, Liron] Denver VA, Aurora, CO USA. [Caplan, Liron] Univ Colorado, Aurora, CO USA. [Cannon, Grant W.] Salt Lake City VA, Salt Lake City, UT USA. [Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. [Lazaro, Deana M.] Brooklyn VA, Brooklyn, NY USA. [Reimold, Andreas M.] Dallas VA, Dallas, TX USA. [Reimold, Andreas M.] Univ Texas SW, Dallas, TX USA. [Johnson, Dannette S.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Cherascu, Bogdan] Iowa City VA, Iowa City, IA USA. [Cherascu, Bogdan] Univ Iowa, Iowa City, IA USA. [Schwab, Pascale] Portland VA, Portland, OR USA. [Schwab, Pascale] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Khan, Nasim A.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Khan, Nasim A.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. [Mikuls, Ted R.] Omaha VA, Omaha, NE USA. [Mikuls, Ted R.] Univ Nebraska, Omaha, NE 68182 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 1174 BP S457 EP S458 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621501368 ER PT J AU Ramos, PS Oates, JC Kamen, DL Gaffney, PM Langefeld, CD Kelly, JA Kaufman, KM Kimberly, RP Niewold, TB Jacob, CO Tsao, BP Brown, E James, JA Guthridge, J Merrill, JT Boackle, SA Freedman, BI Scofield, RH Stevens, AM Vyse, TJ Criswell, LA Moser, KL Alarcon-Riquelme, ME Harley, JB Gilkeson, GS AF Ramos, Paula S. Oates, James C. Kamen, Diane L. Gaffney, Patrick M. Langefeld, Carl D. Kelly, Jennifer A. Kaufman, Kenneth M. Kimberly, Robert P. Niewold, Timothy B. Jacob, Chaim O. Tsao, Betty P. Brown, Elizabeth James, Judith A. Guthridge, Joel Merrill, Joan T. Boackle, Susan A. Freedman, Barry I. Scofield, R. Hal Stevens, Anne M. Vyse, Timothy J. Criswell, Lindsey A. Moser, Kathy L. Alarcon-Riquelme, Marta E. Harley, John B. Gilkeson, Gary S. CA PROFILE TI Association of Reactive Intermediate Genes with Systemic Lupus Erythematosus (SLE) Varies Across Populations with Different African Ancestries SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Ramos, Paula S.; Langefeld, Carl D.; Freedman, Barry I.] Wake Forest Sch Med, Winston Salem, NC USA. [Oates, James C.; Kamen, Diane L.; Gilkeson, Gary S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Kimberly, Robert P.; Brown, Elizabeth; PROFILE] Univ Alabama, Birmingham, AL USA. [Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Boackle, Susan A.] Univ Colorado, Denver Sch Med, Aurora, CO USA. [Stevens, Anne M.] Univ Washington, Seattle, WA 98195 USA. [Vyse, Timothy J.] Kings Coll London, Guys Hosp, London WC2R 2LS, England. [Criswell, Lindsey A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta de Andalucia, Ctr Genom & Oncol Res, Oklahoma Med Res Fdn, Oklahoma City, OK USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 641 BP S250 EP S250 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500637 ER PT J AU Robertson, JM Heinlen, L Anderson, J Niewold, TB Keith, MP Harley, JB James, JA AF Robertson, Julie M. Heinlen, Latisha Anderson, Jourdan Niewold, Timothy B. Keith, Michael P. Harley, John B. James, Judith A. TI Interferon-Alpha Activity Levels Increase Immediately Preceding Clinical Classification of Systemic Lupus SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Robertson, Julie M.; Anderson, Jourdan; James, Judith A.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Heinlen, Latisha] OUHSC, Oklahoma City, OK USA. [Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA. [Keith, Michael P.] Natl Naval Med Ctr, Bethesda, MD USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2601 BP S1022 EP S1022 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621503181 ER PT J AU Sakurai, D Zhao, J Deng, Y Kaufman, K Kelly, JA Kimberly, RP Alarcon-Riquelme, ME Harley, JB Bae, SC Jacob, CO Vyse, TJ Niewold, TB Gaffney, PM Moser, KL James, JA Gilkeson, GS Kamen, DL Langefeld, CD Chang, DM Song, YW Yu, CY Grossman, JM Cantor, RM Hahn, BH Tsao, BP AF Sakurai, Daisuke Zhao, Jian Deng, Yun Kaufman, Kenneth Kelly, Jennifer A. Kimberly, Robert P. Alarcon-Riquelme, Marta E. Harley, John B. Bae, Sang-Cheol Jacob, Chaim O. Vyse, Timothy J. Niewold, Timothy B. Gaffney, Patrick M. Moser, Kathy L. James, Judith A. Gilkeson, Gary S. Kamen, Diane L. Langefeld, Carl D. Chang, Deh-Ming Song, Yeong Wook Yu, Chack-Yung Grossman, Jennifer M. Cantor, Rita M. Hahn, Bevra H. Tsao, Betty P. CA PROFILE Investigators BIOLUPUS GENLES Networ TI Risk Alleles of SLE Associated IL10 SNPs Conferred Differential Binding to Transcription Factors SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Sakurai, Daisuke; Zhao, Jian; Deng, Yun; Grossman, Jennifer M.; Hahn, Bevra H.; Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Kimberly, Robert P.; PROFILE Investigators] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Alarcon-Riquelme, Marta E.; BIOLUPUS GENLES Networ] Oklahoma Med Res Fdn, Ctr Genom & Oncol Res, Oklahoma City, OK 73104 USA. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Harley, John B.] Med Ctr, US Dept Vet Affairs, Cincinnati, OH USA. [Bae, Sang-Cheol] Hanyang Univ, Hosp Rheumat Dis, CRCRA, Seoul 133791, South Korea. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Mol Med, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Immunol, London WC2R 2LS, England. [Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA. [Gaffney, Patrick M.; Moser, Kathy L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Kamen, Diane L.] Med Univ SC, Charleston, SC USA. [Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Chang, Deh-Ming] Natl Def Med Ctr, Taipei, Taiwan. [Song, Yeong Wook] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Yu, Chack-Yung] Nationwide Childrens Hosp, Ctr Mol & Human Genet, Res Inst, Columbus, OH USA. [Yu, Chack-Yung] Ohio State Univ, Columbus, OH 43210 USA. RI Yu, Chack-Yung/E-4360-2011; Zhao, Jian/E-6292-2012 NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2477 BP S966 EP S966 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621503048 ER PT J AU Sanchez, E Comeau, ME Freedman, BI Kelly, JA Kaufman, K Langefeld, CD Brown, EE Merrill, JT Tsao, BP Kamen, DL Gilkeson, GS James, JA Vyse, TJ Gaffney, PM Jacob, CO Niewold, TB Richardson, BC Harley, JB Alarcon-Riquelme, ME Sawalha, AH AF Sanchez, Elena Comeau, Mary E. Freedman, Barry I. Kelly, Jennifer A. Kaufman, Kenneth Langefeld, Carl D. Brown, Elizabeth E. Merrill, J. T. Tsao, Betty P. Kamen, Diane L. Gilkeson, Gary S. James, Judith A. Vyse, Tomothy J. Gaffney, Patrick M. Jacob, Chaim O. Niewold, Timothy B. Richardson, Bruce C. Harley, John B. Alarcon-Riquelme, Marta E. Sawalha, Amr H. TI Identification of Novel Genetic Susceptibility Loci In African-American Lupus Patients Using a Candidate Gene Association Study SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Comeau, Mary E.; Freedman, Barry I.; Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Brown, Elizabeth E.] Univ Alabama, Birmingham, AL USA. [Tsao, Betty P.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Kamen, Diane L.] Med Univ SC, Charleston, SC USA. [Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Vyse, Tomothy J.] Guys Hosp, Univ London Kings Coll, London SE1 9RT, England. [Gaffney, Patrick M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA. [Richardson, Bruce C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Harley, John B.] Med Ctr, US Dept Vet Affairs, Cincinnati, OH USA. [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta Andalucia, Oklahoma Med Res Fdn, Ctr Genom & Oncol Res, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 7 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 OCT PY 2011 VL 63 IS 10 SU S MA 2476 BP S965 EP S966 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621503047 ER PT J AU Sekine, H Machida, T Suzuki, E Reilly, C Zhang, X Ruiz, P Gilkeson, GS AF Sekine, Hidemaru Machida, Takeshi Suzuki, Eiji Reilly, Christopher Zhang, Xian Ruiz, Phil Gilkeson, Gary S. TI Interferon Regulatory Factor-4 deficient Lupus-Prone MRL/LprMice Show Strong Propensity for Th1 Polarity and Develop Granulomatous Lesions in Multiple Organs SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Sekine, Hidemaru; Machida, Takeshi] Fukushima Med Univ, Fukushima, Japan. [Reilly, Christopher] Virginia Tech, Blacksburg, VA USA. [Zhang, Xian] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Ruiz, Phil] Univ Miami, Miami, FL USA. [Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 557 BP S213 EP S213 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500553 ER PT J AU Shah, N Hannon, MJ Wang, ZJ Kwoh, CK AF Shah, Nehal Hannon, Michael J. Wang Zhijie Kwoh, C. Kent TI Relationship of Specific Pain Patterns in Knee Osteoarthritis with Severity of Pain and Functional Disability. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Hannon, Michael J.; Wang Zhijie] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare, Ctr Hlth Equ Res & Promot, 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 1983 BP S770 EP S771 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621502369 ER PT J AU Suzuki, E Williams, S Karam, E Gilkeson, GS Zhang, X AF Suzuki, Eiji Williams, Sarah Karam, Eva Gilkeson, Gary S. Zhang, Xian TI Role of Transcription Factor Fli-1 in Regulation of Dendritic Cell and Monocyte Development SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Suzuki, Eiji; Karam, Eva; Gilkeson, Gary S.; Zhang, Xian] Med Univ S Carolina, Charleston, SC 29425 USA. [Williams, Sarah; Gilkeson, Gary S.; Zhang, Xian] Ralph H Johnson VA Med Ctr, Charleston, SC 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 68 BP S24 EP S24 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500069 ER PT J AU Tjarnlund, A Rider, LG Miller, FW Werth, VP Pilkington, CA de Visser, M Forslund, E Amato, AA Barohn, RJ Bottai, M Finkel, R Paulus, HE Hengstman, GJD Liang, MH Singh, J Lundberg, IE AF Tjarnlund, Anna Rider, Lisa G. Miller, Frederick W. Werth, Victoria P. Pilkington, Clarissa A. de Visser, Marianne Forslund, Elin Amato, Anthony A. Barohn, Richard J. Bottai, Matteo Finkel, Richard Paulus, Harold E. Hengstman, Gerald J. D. Liang, Matthew H. Singh, Jasvinder Lundberg, Ingrid E. TI Ethnic but not Gender Differences in Disease Manifestations in Dermatomyositis Patients SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Bottai, Matteo] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Rider, Lisa G.; Miller, Frederick W.] NIEHS, NIH, Bethesda, MD USA. [Werth, Victoria P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Pilkington, Clarissa A.] Great Ormond St Hosp Sick Children, Dept Rheumatol, London WC1N 3JH, England. [de Visser, Marianne] Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands. [Amato, Anthony A.; Liang, Matthew H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Amato, Anthony A.] Harvard Univ, Sch Med, Boston, MA USA. [Barohn, Richard J.] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, MO USA. [Finkel, Richard] Univ Penn, Childrens Hosp Philadelphia, Dept Neurol, Philadelphia, PA 19104 USA. [Paulus, Harold E.] Univ Calif Los Angeles, Los Angeles, CA USA. [Hengstman, Gerald J. D.] Catharina Hosp, Dept Neurol, Eindhoven, Netherlands. [Singh, Jasvinder] Univ Alabama, Birmingham, AL USA. [Singh, Jasvinder] VA Med Ctr, Birmingham, AL 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 235 BP S87 EP S87 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500235 ER PT J AU Vashisht, P Sayles, H Cannon, GW Kerr, GS Schwab, P Lazaro, DM Reimold, AM Khan, NA Cherascu, B Gaffo, AL Johnson, DS Mikuls, TR Michaud, K AF Vashisht, Priyanka Sayles, Harlan Cannon, Grant W. Kerr, Gail S. Schwab, Pascale Lazaro, Deana M. Reimold, Andreas M. Khan, Nasim A. Cherascu, Bogdan Gaffo, Angelo L. Johnson, Dannette S. Mikuls, Ted R. Michaud, Kaleb TI Generalizability of Patients with Rheumatoid Arthritis in Biologic Clinical Trials SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Vashisht, Priyanka] Creighton Univ, Med Ctr, Omaha, NE USA. [Sayles, Harlan; Mikuls, Ted R.; Michaud, Kaleb] Univ Nebraska Med Ctr, Omaha, NE USA. [Cannon, Grant W.] Salt Lake City VA, Salt Lake City, UT USA. [Kerr, Gail S.] Washington DC VA, Washington, DC USA. [Schwab, Pascale] Portland VA, Portland, OR USA. [Lazaro, Deana M.] Brooklyn VA, Brooklyn, NY USA. [Reimold, Andreas M.] Dallas VA, Dallas, TX USA. [Khan, Nasim A.] Univ Arkansas Med Sci & Cent Arkansas Vet Healthc, Little Rock, AR USA. [Cherascu, Bogdan] Iowa City VA, Iowa City, IA USA. [Gaffo, Angelo L.] Birmingham VA Med Ctr, Birmingham, AL USA. [Johnson, Dannette S.] Jackson VA, Jackson, MS USA. [Mikuls, Ted R.] Omaha VA, Omaha, NE USA. [Michaud, Kaleb] Natl Data Bank Rheumat Dis, Omaha, NE USA. [Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. [Kerr, Gail S.] Georgetown Univ, Washington, DC USA. [Schwab, Pascale] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Reimold, Andreas M.] Univ Texas SW, Dallas, TX USA. [Cherascu, Bogdan] Univ Iowa, Iowa City, IA USA. [Johnson, Dannette S.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 1200 BP S467 EP S467 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621501394 ER PT J AU Zhao, J Sakurai, D Deng, Y Sestak, AL Langefeld, CD Kaufman, KM Kelly, JA Gaffney, PM Moser, KL Alarcon-Riquelme, ME Harley, JB Bae, SC Vyse, TJ Jacob, CO Kimberly, RP Criswell, LA James, JA Gilkeson, GS Anaya, JM Chang, DM Song, YW Grossman, JM Hahn, BH Cantor, RM Tsao, BP AF Zhao, Jian Sakurai, Daisuke Deng, Yun Sestak, Andrea L. Langefeld, Carl D. Kaufman, Kenneth M. Kelly, Jennifer A. Gaffney, Patrick M. Moser, Kathy L. Alarcon-Riquelme, Marta E. Harley, John B. Bae, Sang-Cheol Vyse, Timothy J. Jacob, Chaim O. Kimberly, Robert P. Criswell, Lindsey A. James, Judith A. Gilkeson, Gary S. Anaya, Juan-Manuel Chang, Deh-Ming Song, Yeong W. Grossman, Jennifer M. Hahn, Bevra H. Cantor, Rita M. Tsao, Betty P. CA BIOLUPUS GENLES Network PROFILE Investigators TI SLE-Risk Alleles of SNPs in the NMNAT2/SMG7 Region Are Associated with Lower mRNA Levels of SMG7 SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Zhao, Jian; Sakurai, Daisuke; Deng, Yun; Grossman, Jennifer M.; Hahn, Bevra H.; Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Sestak, Andrea L.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Kaufman, Kenneth M.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Gaffney, Patrick M.; Moser, Kathy L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Alarcon-Riquelme, Marta E.; BIOLUPUS GENLES Network] Pfizer Univ Granada Junda de Andalucia GENYO, Ctr Genom & Invest Oncol, Granada, Spain. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Bae, Sang-Cheol] Hanyang Univ, Hosp Rheumat Dis, CRCRA, Seoul 133791, South Korea. [Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Mol Med & Immunol, London WC2R 2LS, England. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Kimberly, Robert P.; PROFILE Investigators] Univ Alabama, Birmingham, AL USA. [Criswell, Lindsey A.] Univ Calif San Francisco, Dept Med, Rosaling Russell Med Res Ctr Arthrit, San Francisco, CA USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Anaya, Juan-Manuel] Univ Rosario, Corp Invest Biol, Bogota, Colombia. [Chang, Deh-Ming] Natl Def Med Ctr, Taipei, Taiwan. [Song, Yeong W.] Seoul Natl Univ, Seoul, South Korea. RI Zhao, Jian/E-6292-2012; Anaya, Juan-Manuel/J-1960-2016 OI Anaya, Juan-Manuel/0000-0002-6444-1249 NR 0 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 639 BP S249 EP S249 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500635 ER PT J AU Wang, DB Gitcho, MA Kraemer, BC Klein, RL AF Wang, David B. Gitcho, Michael A. Kraemer, Brian C. Klein, Ronald L. TI Genetic strategies to study TDP-43 in rodents and to develop preclinical therapeutics for amyotrophic lateral sclerosis SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Review DE adeno-associated virus; amyotrophic lateral sclerosis; frontotemporal lobar degeneration; gene therapy; gene transfer ID FRONTOTEMPORAL LOBAR DEGENERATION; ADENOASSOCIATED VIRUS VECTORS; SPINAL MUSCULAR-ATROPHY; MOTOR-NEURON DISEASE; TRANSGENIC ALS MICE; BINDING PROTEIN 43; NEUROTROPHIC FACTOR; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE AB The neuropathological hallmark of the majority of amyotrophic lateral sclerosis (ALS) and a class of frontotemporal lobar degeneration is ubiquitinated cytoplasmic aggregates composed of transactive response DNA binding protein 43 kDa (TDP-43). Genetic manipulation of TDP-43 in animal models has been used to study the proteins role in pathogenesis. Transgenic rodents for TDP-43 have recapitulated key aspects of ALS such as paralysis, loss of spinal motor neurons and muscle atrophy. Viral vectors are an alternate approach to express pathological proteins in animals. Use of the recombinant adeno-associated virus vector serotype 9 has permitted widespread transgene expression throughout the central nervous system after intravenous administration. Expressing TDP-43 in rats with this method produced a phenotype that was consistent with and similar to TDP-43 transgenic lines. Increased levels of TDP-43 in the nucleus are toxic to neurons and sufficient to produce ALS-like symptoms. Animal models based on TDP-43 will address the relationships between TDP-43 expression levels, pathology, neuronal loss, muscle atrophy, motor function and causative mechanisms of disease. New targets that modify TDP-43 function, or targets from previous ALS models and other models of spinal cord diseases, could be tested for efficacy in the recent rodent models of ALS based on TDP-43. The vector approach could be an important therapeutic channel because the entire spinal cord can be affected from a one-time peripheral administration. C1 [Wang, David B.; Klein, Ronald L.] Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol Toxicol & Neurosci, Shreveport, LA 71105 USA. [Gitcho, Michael A.] Univ Wisconsin, Div Pharmaceut Sci, Madison, WI USA. [Kraemer, Brian C.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Kraemer, Brian C.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Klein, RL (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol Toxicol & Neurosci, Shreveport, LA 71105 USA. EM klein@lsuhsc.edu FU Department of Veterans Affairs [1147891]; NIH/NINDS [R01 NS048450] FX David Knight and R. Waleed Naseem critiqued the manuscript. This work was supported by Department of Veterans Affairs Merit Review Grant 1147891 (B.C.K.) and NIH/NINDS R01 NS048450 (R.L.K.). NR 112 TC 9 Z9 10 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD OCT PY 2011 VL 34 IS 8 BP 1179 EP 1188 DI 10.1111/j.1460-9568.2011.07803.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 847ZC UT WOS:000297014000001 PM 21777407 ER PT J AU Hu, YQ Ledoux, WR Fassbind, M Rohr, ES Sangeorzan, BJ Haynor, D AF Hu, Yangqiu Ledoux, William R. Fassbind, Michael Rohr, Eric S. Sangeorzan, Bruce J. Haynor, David TI Multi-Rigid Image Segmentation and Registration for the Analysis of Joint Motion From Three-Dimensional Magnetic Resonance Imaging SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE joint motion; MRI; segmentation; registration; visualization ID ANKLE JOINT; SUBTALAR; KINEMATICS; FOOT; MR; COMPLEX AB We report an image segmentation and registration method for studying joint morphology and kinematics from in vivo magnetic resonance imaging (MRI) scans and its application to the analysis of foot and ankle joint motion. Using an MRI-compatible positioning device, a foot was scanned in a single neutral and seven other positions ranging from maximum plantar flexion, inversion, and internal rotation to maximum dorsiflexion, eversion, and external rotation. A segmentation method combining graph cuts and level set was developed. In the subsequent registration step, a separate rigid body transformation for each bone was obtained by registering the neutral position dataset to each of the other ones, which produced an accurate description of the motion between them. The segmentation algorithm allowed a user to interactively delineate 14 foot bones in the neutral position volume in less than 30 min total (user and computer processing unit [CPU]) time. Registration to the seven other positions took approximately 10 additional minutes of user time and 5.25 h of CPU time. For validation, our results were compared with those obtained from 3DViewnix, a semiautomatic segmentation program. We achieved excellent agreement, with volume overlap ratios greater than 88% for all bones excluding the intermediate cuneiform and the lesser metatarsals. For the registration of the neutral scan to the seven other positions, the average overlap ratio is 94.25%, while the minimum overlap ratio is 89.49% for the tibia between the neutral position and position 1, which might be due to different fields of view (FOV). To process a single foot in eight positions, our tool requires only minimal user interaction time (less than 30 min total), a level of improvement that has the potential to make joint motion analysis from MRI practical in research and clinical applications. [DOI: 10.1115/1.4005175] C1 [Hu, Yangqiu; Haynor, David] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Hu, Yangqiu; Haynor, David] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Ledoux, William R.; Fassbind, Michael; Rohr, Eric S.; Sangeorzan, Bruce J.] VA Ctr Excellence Limb Loss Prevent & Prosthet En, Seattle, WA 98108 USA. [Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Ledoux, William R.; Sangeorzan, Bruce J.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), 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 National Institute of Arthritis and Musculoskeletal and Skin Diseases [5P60AR048093-03]; Department of Veterans Affairs [A2661C] FX This research was partially supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases under Grant 5P60AR048093-03, and by the Department of Veterans Affairs, Rehabilitation Research and Development Grant A2661C. NR 34 TC 6 Z9 6 U1 0 U2 8 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD OCT PY 2011 VL 133 IS 10 AR 101005 DI 10.1115/1.4005175 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 846CN UT WOS:000296874900005 PM 22070330 ER PT J AU Medalia, C Chang, VW AF Medalia, Carla Chang, Virginia W. TI Gender equality, development, and cross-national sex gaps in life expectancy SO INTERNATIONAL JOURNAL OF COMPARATIVE SOCIOLOGY LA English DT Article DE cross-national; development; gender equality; life expectancy; sex differences ID WOMENS HEALTH; FEMALE MORTALITY; RISK-FACTOR; COUNTRIES; SMOKING; CONVERGENCE; INEQUALITY; EMPLOYMENT; COHORT; MEN AB Female life expectancy exceeds male life expectancy in almost every country throughout the world. Nevertheless, cross-national variation in the sex gap suggests that social factors, such as gender equality, may directly affect or mediate an underlying biological component. In this article, we examine the association between gender equality and the sex gap in mortality. Previous research has not addressed this question from an international perspective with countries at different levels of development. We examine 131 countries using a broad measure of national gender equality that is applicable in both Less Developed Countries (LDCs) and Highly Developed Countries (HDCs). We find that the influence of gender equality is conditional on level of development. While gender equality is associated with divergence between female and male life expectancies in LDCs, it is associated with convergence in HDCs. The relationship between gender equality and the sex gap in mortality in HDCs strongly relates to, but is not explained by, sex differences in lung cancer mortality. Finally, we find that divergence in LDCs is primarily driven by a strong positive association between gender equality and female life expectancy. In HDCs, convergence is potentially related to a weak negative association between gender equality and female life expectancy, though findings are not statistically significant. C1 [Medalia, Carla] Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. [Chang, Virginia W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Medalia, C (reprint author), Univ Penn, Dept Sociol, McNeil Bldg,Ste 113,3718 Locust Walk, Philadelphia, PA 19104 USA. EM medalia@sas.upenn.edu NR 58 TC 5 Z9 5 U1 2 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0020-7152 J9 INT J COMP SOCIOL JI Int. J. Comp. Sociol. PD OCT PY 2011 VL 52 IS 5 BP 371 EP 389 DI 10.1177/0020715211426177 PG 19 WC Sociology SC Sociology GA 846TA UT WOS:000296924900001 ER PT J AU Kamnaksh, A Kovesdi, E Kwon, SK Wingo, D Ahmed, F Grunberg, NE Long, J Agoston, DV AF Kamnaksh, Alaa Kovesdi, Erzsebet Kwon, Sook-Kyung Wingo, Daniel Ahmed, Farid Grunberg, Neil E. Long, Joseph Agoston, Denes V. TI Factors Affecting Blast Traumatic Brain Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE behavior; inflammation; traumatic brain injury ID POSTTRAUMATIC-STRESS-DISORDER; INDUCED NEUROTRAUMA; CEREBRAL-ISCHEMIA; INFLAMMATION; NEUROPROTECTION; MECHANISMS; EXPRESSION; CYTOKINES; EXPOSURE; IMMUNE AB The overlapping pathologies and functional outcomes of blast-induced TBI (bTBI) and stress-related neurobehavioral disorders like post-traumatic stress disorder (PTSD) are significant military health issues. Soldiers are exposed to multiple stressors with or without suffering bTBI, making diagnosis and treatment as well as experimental modeling of bTBI a challenge. In this study we compared anxiety levels of Naive rats to ones that were exposed to each of the following conditions daily for 4 consecutive days: C I: transportation alone; C II: transportation and anesthesia; C III: transportation, anesthesia, and blast sounds; Injured: all three variables plus mild blast overpressure. Following behavioral testing we analyzed sera and select brain regions for protein markers and cellular changes. C I, C II, and C III animals exhibited increased anxiety, but serum corticosterone levels were only significantly elevated in C III and Injured rats. C III and Injured animals also had elevated interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) levels in the amygdala (AD) and ventral hippocampus (VHC). Glial fibrillary acidic protein (GFAP) levels were only significantly elevated in the VHC, prefrontal cortex (PFC), and AD of Injured animals; they showed an apparent increase in ionized calcium-binding adapter molecule (Iba1) and GFAP immunoreactivity, as well as increased numbers of TUNEL-positive cells in the VHC. Our findings demonstrate that experimental conditions, particularly the exposure to blast acoustics, can increase anxiety and trigger specific behavioral and molecular changes without injury. These findings should be taken into consideration when designing bTBI studies, to better understand the role of stressors in the development of post-traumatic symptoms, and to establish a differential diagnosis for PTSD and bTBI. C1 [Agoston, Denes V.] Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Grunberg, Neil E.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. [Kamnaksh, Alaa; Kwon, Sook-Kyung; Ahmed, Farid; Grunberg, Neil E.; Agoston, Denes V.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Kovesdi, Erzsebet] US Dept Vet Affairs, Vet Affairs Cent Off, Washington, DC USA. [Long, Joseph] Walter Reed Army Inst Res, Ctr Mil Psychiat & Neurotrauma, Blast Induced Neurotrauma Branch, Silver Spring, MD USA. RP Agoston, DV (reprint author), Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM vagoston@usuhs.edu FU Center for Neuroscience and Regenerative Medicine (CNRM) [G1703F] FX We thank the Neurotrauma Team (WRAIR) for their technical help during the exposures. This work was supported by Center for Neuroscience and Regenerative Medicine (CNRM) grant no. G1703F. NR 46 TC 44 Z9 44 U1 1 U2 9 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2011 VL 28 IS 10 BP 2145 EP 2153 DI 10.1089/neu.2011.1983 PG 9 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 839OX UT WOS:000296378500015 PM 21861635 ER PT J AU Flanagan, ME Welsh, CA Kiess, C Hoke, S Doebbeling, BN AF Flanagan, Mindy E. Welsh, Catherine Amber Kiess, Chris Hoke, Shawn Doebbeling, Bradley N. CA HAI Collaborative TI A national collaborative for reducing health care-associated infections: Current initiatives, challenges, and opportunities SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Hospital-acquired infections; infection prevention and control ID HOSPITAL-ACQUIRED INFECTIONS; BLOOD-STREAM INFECTIONS; NOSOCOMIAL INFECTIONS; EDUCATION-PROGRAM; STAY; INTERVENTION; SAFETY; LENGTH; IMPACT; COSTS AB There has been increasing interest and an upsurge in efforts to prevent hospital-associated infections (HAIs), a leading cause of death in the United States. This study was conducted to assess current strategies and efforts of HAI reduction initiatives in hospitals. HAI reduction initiatives and factors influencing institutional participation in these initiatives were categorized. Data were collected via open-ended questions on surveys performed in 5 different HAI collaboratives. Thematic analysis of the coded qualitative data was conducted. A total of 1,212 health care professionals from 33 different hospitals participated. Improving hand hygiene was the most frequently mentioned HAI reduction initiative implemented in the previous year. Initiatives for reducing central line or central venous catheter infections and ventilator-associated pneumonia also were commonly cited. The most frequently mentioned challenges to implementing HAI reduction initiatives included poor adherence, insufficient resources, staffing problems, lack of culture change, no impetus to change, and issues related to staff and patient education. Many respondents identified engaging physicians as particularly challenging. These findings suggest that consistently improving hand hygiene remains a widespread problem for reducing HAIs and sustaining this type of behavioral change is difficult. Furthermore, ensuring staff and physician engagement and compliance in HAI reduction efforts remains challenging for most hospitals. C1 [Flanagan, Mindy E.; Doebbeling, Bradley N.] Indiana Univ, Ctr Hlth Serv & Outcomes Res, Indianapolis, IN 46204 USA. [Welsh, Catherine Amber; Doebbeling, Bradley N.] Regenstrief Inst Inc, Indianapolis, IN USA. [Kiess, Chris; Hoke, Shawn; Doebbeling, Bradley N.] US Dept Vet Affairs, Hlth Serv Res & Dev Ctr Excellence, Indianapolis, IN USA. [Doebbeling, Bradley N.] Roudebush VAMC, VA HSR&D Ctr Implementing Evidence Based Practice, Indianapolis, IN USA. [Doebbeling, Bradley N.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. RP Flanagan, ME (reprint author), 10 W 10th St,Suite 2000, Indianapolis, IN 46202 USA. EM meflanag@iupui.edu FU Agency for Heathcare Research and Quality [HHSA290200600013I] FX This research was supported by the Agency for Heathcare Research and Quality (Contract HHSA290200600013I, Task Order 4). NR 18 TC 16 Z9 16 U1 2 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD OCT PY 2011 VL 39 IS 8 BP 685 EP 689 DI 10.1016/j.ajic.2010.12.013 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 841TH UT WOS:000296535700013 PM 21665329 ER PT J AU Palileo, C Kaunitz, JD AF Palileo, Coleen Kaunitz, Jonathan D. TI Gastrointestinal defense mechanisms SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE lipopolysaccharides; matrix metalloproteinase; prostaglandin E synthase; proton pump inhibitor; trefoil factors ID GASTRODUODENAL MUCOSAL DEFENSE; BICARBONATE SECRETION; SENSORY NEURONS; GASTRIC-ULCERS; INDOMETHACIN; INJURY; ANGIOGENESIS; LANSOPRAZOLE; INHIBITORS; MELATONIN AB Purpose of review We have highlighted the recent findings relating to gastroduodenal mucosal defense, including elements that may contribute to the failure of defense systems and factors that enhance mucosal healing, focusing on findings that elucidate new pathophysiological mechanisms. Recent findings Bicarbonate secretion is mediated by multiple types of prostaglandin E synthases, including membrane-bound prostaglandin E synthase-1. Mucins, growth factors, and trefoil factors are involved in accelerating gastric injury healing through epithelial reconstruction. A combination of NSAIDs and bile induce greater damage on the mucosa than if the two agents were acting alone. Proton pump inhibitors defend the mucosa from injury by promoting cellular restitution as well as inhibiting gastric acid secretion and reactive oxygen species (ROS) damage. Roxatidine, a novel H-2 receptor antagonist, acts through a mechanism that involves nitric oxide. Melatonin enhances angiogenesis through the upregulation of plasma levels of gastrin and matrix metalloproteinase expression. The mucosal protective drug polaprezinc exhibits ROS-quenching activities. Lipopolysaccharides induce oxidative stress mediated by p38 mitogen-activated protein kinase (p38 MAPK). Aging weakens gastroduodenal mucosal defense mechanisms. Summary There is a wide array of pathways leading to gastroduodenal mucosal injury in addition to protective defense mechanisms that counteract them to maintain homeostasis. Increased understanding of these systems may help identify novel molecular targets for the prevention and treatment of mucosal injury. C1 [Palileo, Coleen; Kaunitz, Jonathan D.] Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, W Los Angeles Vet Affairs Med Ctr, David Geffen Sch Med, Los Angeles, CA 90073 USA. [Palileo, Coleen] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, David Geffen Sch Med, Los Angeles, CA 90073 USA. [Palileo, Coleen; Kaunitz, Jonathan D.] Univ Calif Los Angeles, David Geffen Sch Med, Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, W Los Angeles Vet Affairs Med Ctr, David Geffen Sch Med, Bldg 114,Suite 217E,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU VA Merit Review; NIH/NIDDK [R01 DK54221] FX This study was supported by VA Merit Review funding and NIH/NIDDK R01 DK54221 (J.D.K.). NR 39 TC 22 Z9 25 U1 0 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD OCT PY 2011 VL 27 IS 6 BP 543 EP 548 DI 10.1097/MOG.0b013e32834b3fcb PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 836WN UT WOS:000296148000010 PM 21897225 ER PT J AU Sher, L AF Sher, Leo TI Teaching medical staff in general hospitals about suicide prevention SO JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION LA English DT Letter ID INPATIENT SUICIDE C1 James J Peters Vet Adm Med Ctr, Dept Psychiat, Mt Sinai Sch Med, Bronx, NY 10468 USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, Dept Psychiat, Mt Sinai Sch Med, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM DrLeoSher@gmail.com NR 4 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER TAIWAN PI TAIPEI PA RM N-412, 4F, CHIA HSIN BUILDING 11, NO 96, ZHONG SHAN N ROAD SEC 2, TAIPEI, 10449, TAIWAN SN 0929-6646 J9 J FORMOS MED ASSOC JI J. Formos. Med. Assoc. PD OCT PY 2011 VL 110 IS 10 BP 664 EP 664 DI 10.1016/j.jfma.2011.08.011 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 843IM UT WOS:000296665500011 PM 21982473 ER PT J AU Factor, SA Steenland, NK Higgins, DS Molho, ES Kay, DM Montimurro, J Rosen, AR Zabetian, CP Payami, H AF Factor, Stewart A. Steenland, N. Kyle Higgins, Donald S. Molho, Eric S. Kay, Denise M. Montimurro, Jennifer Rosen, Ami R. Zabetian, Cyrus P. Payami, Haydeh TI Disease-Related and Genetic Correlates of Psychotic Symptoms in Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; psychosis; depression; sleep; freezing of gait; genetics; risk factors ID VISUAL HALLUCINATIONS; RISK-FACTORS; LEWY BODIES; DEMENTIA; POLYMORPHISMS; ASSOCIATION; FREQUENCY; LEVODOPA; CHOLECYSTOKININ; PREVALENCE AB Our aim was to examine disease-related and genetic correlates of the development of psychotic symptoms in a large population of patients with Parkinson's disease. We studied 500 patients with Parkinson's disease from the NeuroGenetics Research Consortium using logistic regression models. Predictors were demographic, clinical (motor/nonmotor features), and genetic, measured as continuous or dichotomous variables. Continuous measures were divided into population-based tertiles. Results are given as odds ratios (95% confidence intervals) for dichotomous variables and by ascending tertile for continuous variables. Psychotic symptoms were associated with increasing age: 4.86 (1.62-14.30) and 6.25 (2.09-18.74) (test for trend: P = 0.01); and duration of disease: 3.81 (1.23-11.76) and 5.33 (1.68-16.89) (test for trend: P = 0.03). For nonmotor features, we demonstrated positive trends with depression: 1.31 (0.47-3.61) and 5.01 (2.04-12.33) (test for trend: P < 0.0001); cognitive dysfunction: 0.69 (0.26-1.84) and 2.51 (1.00-6.29) (test for trend: P 5 0.03); and an excess for those with sleep disorders: 2.00 (1.03-3.89) (P = 0.04). Psychotic symptoms were not associated with tremor or postural instability scores, but there was an association with freezing of gait: 3.83 (1.67-8.75) (P < 0.002). Psychotic symptoms were not associated with the presence of any examined polymorphisms in the apolipoprotein, alpha-synuclein, or microtubule associated protein tau genes. This is the largest study to examine correlates of psychotic symptoms in Parkinson's disease. We discovered a novel association with freezing of gait. We demonstrated an association with depression and duration of disease, both of which were inconsistently related in previous studies, and confirmed the association with age, cognitive dysfunction, and sleep disorders. (C) 2011 Movement Disorder Society C1 [Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30329 USA. [Higgins, Donald S.] Samuel Stratton Vet Affairs Med Ctr, Albany, NY USA. [Molho, Eric S.] Albany Med Ctr, Albany, NY USA. [Kay, Denise M.; Montimurro, Jennifer; Payami, Haydeh] New York State Dept Hlth, Albany, NY USA. [Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Zabetian, Cyrus P.] Univ Washington, Seattle, WA USA. RP Factor, SA (reprint author), Emory Univ, Sch Med, Dept Neurol, 1841 Clifton Rd NE, Atlanta, GA 30329 USA. EM sfactor@emory.edu OI Kay, Denise/0000-0002-9928-2698; Zabetian, Cyrus/0000-0002-7739-4306 FU Michael J. Fox Foundation; Close to a Cure Foundation; NIH [R01-NS36960]; Department of Veterans Affairs; New York State Department of Health Wadsworth Center; Sartain Lanier Family Foundation; Riley Family Chair in Parkinson's Disease; Teva Neurosciences; Ipsen; Ceregene; Consolidated Anti-aging Foundation; Allergan; EMD Serono; Impax Pharmaceuticals; Acadia Pharmaceuticals; Merz Pharmaceuticals FX Funding agencies: Michael J. Fox Foundation: Edmond J. Safra Global Genetics Consortia Grant; Close to a Cure Foundation: A Fund for Parkinson's Research of Foundation for the Carolinas; NIH: R01-NS36960, Department of Veterans Affairs Merit Review Award; New York State Department of Health Wadsworth Center; The Sartain Lanier Family Foundation; and the Riley Family Chair in Parkinson's Disease.; Stewart A. Factor has research grants from Teva Neurosciences, Ipsen, Ceregene, the Michael J. Fox Foundation, and the Consolidated Anti-aging Foundation and also was a consultant for Boehringer-Ingelheim. Eric S. Molho has received research grants from Teva Neurosciences, Allergan, EMD Serono, Impax Pharmaceuticals, and Acadia Pharmaceuticals and has received consulting fees from Allergan, Merz Pharmaceuticals, and Ipsen. NR 49 TC 20 Z9 20 U1 0 U2 6 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 OCT PY 2011 VL 26 IS 12 BP 2190 EP 2195 DI 10.1002/mds.23806 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 842PH UT WOS:000296610900012 PM 21714002 ER PT J AU Seppi, K Weintraub, D Coelho, M Perez-Lloret, S Fox, SH Katzenschlager, R Hametner, EM Poewe, W Rascol, O Goetz, CG Sampaio, C AF Seppi, Klaus Weintraub, Daniel Coelho, Miguel Perez-Lloret, Santiago Fox, Susan H. Katzenschlager, Regina Hametner, Eva-Maria Poewe, Werner Rascol, Olivier Goetz, Christopher G. Sampaio, Cristina TI The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the Non-Motor Symptoms of Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Review DE Parkinson's disease; evidence-based medicine; dopamine agonists; tricyclic antidepressants; selective serotonin reuptake inhibitors (SSRIs); omega-3 fatty-acids; transcranial magnetic stimulation ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; BOTULINUM-TOXIN-A; DOPAMINERGIC-INDUCED HALLUCINATIONS; TRANSCRANIAL MAGNETIC STIMULATION; QUALITY STANDARDS SUBCOMMITTEE; DRUG-INDUCED PSYCHOSIS; ACADEMY-OF-NEUROLOGY; SCALE MDS-UPDRS; DOUBLE-BLIND AB The Movement Disorder Society (MDS) Task Force on Evidence-Based Medicine (EBM) Review of Treatments for Parkinson's Disease (PD) was first published in 2002 and was updated in 2005 to cover clinical trial data up to January 2004 with the focus on motor symptoms of PD. In this revised version the MDS task force decided it was necessary to extend the review to non-motor symptoms. The objective of this work was to update previous EBM reviews on treatments for PD with a focus on non-motor symptoms. Level-I (randomized controlled trial, RCT) reports of pharmacological and nonpharmacological interventions for the non-motor symptoms of PD, published as full articles in English between January 2002 and December 2010 were reviewed. Criteria for inclusion and ranking followed the original program outline and adhered to EBM methodology. For efficacy conclusions, treatments were designated: efficacious, likely efficacious, unlikely efficacious, non-efficacious, or insufficient evidence. Safety data were catalogued and reviewed. Based on the combined efficacy and safety assessment, Implications for clinical practice were determined using the following designations: clinically useful, possibly useful, investigational, unlikely useful, and not useful. Fifty-four new studies qualified for efficacy review while several other studies covered safety issues. Updated and new efficacy conclusions were made for all indications. The treatments that are efficacious for the management of the different non-motor symptoms are as follows: pramipexole for the treatment of depressive symptoms, clozapine for the treatment of psychosis, rivastigmine for the treatment of dementia, and botulinum toxin A (BTX-A) and BTX-B as well as glycopyrrolate for the treatment of sialorrhea. The practical implications for these treatments, except for glycopyrrolate, are that they are clinically useful. Since there is insufficient evidence of glycopyrrolate for the treatment of sialorrhea exceeding 1 week, the practice implication is that it is possibly useful. The treatments that are likely efficacious for the management of the different non-motor symptoms are as follows: the tricyclic antidepressants nortriptyline and desipramine for the treatment of depression or depressive symptoms and macrogol for the treatment of constipation. The practice implications for these treatments are possibly useful. For most of the other interventions there is insufficient evidence to make adequate conclusions on their efficacy. This includes the tricyclic antidepressant amitriptyline, all selective serotonin reuptake inhibitors (SSRIs) reviewed (paroxetine, citalopram, sertraline, and fluoxetine), the newer antidepressants atomoxetine and nefazodone, pergolide, Omega-3 fatty acids as well as repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression or depressive symptoms; methylphenidate and modafinil for the treatment of fatigue; amantadine for the treatment of pathological gambling; donepezil, galantamine, and memantine for the treatment of dementia; quetiapine for the treatment of psychosis; fludrocortisone and domperidone for the treatment of orthostatic hypotension; sildenafil for the treatment of erectile dysfunction, ipratropium bromide spray for the treatment of sialorrhea; levodopa/carbidopa controlled release (CR), pergolide, eszopiclone, melatonin 3 to 5 mg and melatonin 50 mg for the treatment of insomnia and modafinil for the treatment of excessive daytime sleepiness. Due to safety issues the practice implication is that pergolide and nefazodone are not usful for the above-mentioned indications. Due to safety issues, olanzapine remains not useful for the treatment of psychosis. As none of the studies exceeded a duration of 6 months, the recommendations given are for the short-term management of the different non-motor symptoms. There were no RCTs that met inclusion criteria for the treatment of anxiety disorders, apathy, medication-related impulse control disorders and related behaviors other than pathological gambling, rapid eye movement (REM) sleep behavior disorder (RBD), sweating, or urinary dysfunction. Therefore, there is insufficient evidence for the treatment of these indications. This EBM review of interventions for the non-motor symptoms of PD updates the field, but, because several RCTs are ongoing, a continual updating process is needed. Several interventions and indications still lack good quality evidence, and these gaps offer an opportunity for ongoing research. (C) 2011 Movement Disorder Society C1 [Sampaio, Cristina] Univ Lisbon, Inst Med Mol, P-1699 Lisbon, Portugal. [Seppi, Klaus; Hametner, Eva-Maria; Poewe, Werner] Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria. [Weintraub, Daniel] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis & Mental Illness Res Educ & Clin C, Philadelphia, PA USA. [Seppi, Klaus] Philadelphia Vet Affairs Med Ctr, MIRECC, Philadelphia, PA USA. [Coelho, Miguel] Hosp Santa Maria, Neurol Clin Res Unit, Inst Med Mol, Lisbon, Portugal. [Perez-Lloret, Santiago; Rascol, Olivier] Toulouse Univ Hosp, Dept Clin Pharmacol, Toulouse, France. [Fox, Susan H.] Toronto Western Hosp, Movement Disorder Clin, Toronto, ON, Canada. [Katzenschlager, Regina] Danube Hosp SMZ Ost, Dept Neurol, Vienna, Austria. [Goetz, Christopher G.] Rush Univ Med Ctr, Dept Neurol Sci, Chicago, IL USA. RP Sampaio, C (reprint author), Univ Lisbon, Inst Med Mol, P-1699 Lisbon, Portugal. EM klaus.seppi@uki.at; crissampaio@mac.com OI Coelho, Miguel/0000-0002-4008-8110 FU MDS; Teva pharmaceuticals FX This work was supported by the MDS and an unrestricted educational grant from Teva pharmaceuticals. NR 118 TC 265 Z9 275 U1 12 U2 96 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT PY 2011 VL 26 SU 3 BP S42 EP S80 DI 10.1002/mds.23884 PG 39 WC Clinical Neurology SC Neurosciences & Neurology GA 842PN UT WOS:000296611500003 PM 22021174 ER PT J AU Won, SJ Tang, XN Suh, SW Yenari, MA Swanson, RA AF Won, Seok Joon Tang, Xian Nan Suh, Sang Won Yenari, Midori A. Swanson, Raymond A. TI Hyperglycemia Promotes Tissue Plasminogen Activator-Induced Hemorrhage by Increasing Superoxide Production SO ANNALS OF NEUROLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; GLOBAL CEREBRAL-ISCHEMIA; BRAIN LACTIC-ACIDOSIS; NADPH OXIDASE; INTRACEREBRAL HEMORRHAGE; CANADIAN ALTEPLASE; OXIDATIVE STRESS; GLUCOSE LEVEL; INFARCT SIZE; CELL-DAMAGE AB Objective: Risk of intracerebral hemorrhage is the primary factor limiting use of tissue plasminogen activator (tPA) for stroke. Clinical studies have established an association between admission hyperglycemia and the risk of hemorrhage with tPA use, independent of prior diabetes. Here we used an animal model of tPA-induced reperfusion hemorrhage to determine if this clinical association reflects a true causal relationship. Methods: Rats underwent 90 minutes of focal ischemia, and tPA infusion was begun 10 minutes prior to vessel reperfusion. Glucose was administered during ischemia to generate blood levels ranging from 5.9 +/- 1.8mM (normoglycemia) to 21 +/- 2.3mM. In some studies, apocynin was administered to block superoxide production by nicotinamide adenine dinucleotide phosphate (NADPH). Brains were harvested 1 hour or 3 days after reperfusion to evaluate the effects of hyperglycemia and apocynin on oxidative stress, blood-brain barrier breakdown, infarct volume, and hemorrhage volume. Results: Rats that were hyperglycemic during tPA infusion had diffusely increased blood-brain barrier permeability in the postischemic territory, and a 3- to 5-fold increase in intracerebral hemorrhage volumes. The hyperglycemic rats also showed increased superoxide formation in the brain parenchyma and vasculature during reperfusion. The effects of hyperglycemia on superoxide production, blood-brain barrier disruption, infarct size, and hemorrhage were all attenuated by apocynin. Interpretation: These findings demonstrate a causal relationship between hyperglycemia and hemorrhage in an animal model of tPA stroke treatment, and suggest that this effect of hyperglycemia is mediated through an increase in superoxide production by NADPH oxidase. ANN NEUROL 2011;70:583-590 C1 San Francisco VA Med Ctr, Neurol & Rehabil Serv, San Francisco, CA USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. RP Swanson, RA (reprint author), 127 Neurol VAMC, 4150 Clement St, San Francisco, CA 94121 USA. EM raymond.swanson@ucsf.edu OI Swanson, Raymond/0000-0002-3664-5359 FU US Department of Veterans Affairs; National Institutes of Health [P50 NS14543] FX This work was supported by the US Department of Veterans Affairs and National Institutes of Health (P50 NS14543; R. A. S. and M.A.Y.). S.J.W. and X.N.T. contributed equally to this work. NR 47 TC 49 Z9 52 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2011 VL 70 IS 4 BP 583 EP 590 DI 10.1002/ana.22538 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 839VD UT WOS:000296396700011 PM 22002675 ER PT J AU Tang, XN Zheng, Z Giffard, RG Yenari, MA AF Tang, Xian N. Zheng, Zhen Giffard, Rona G. Yenari, Midori A. TI Significance of Marrow-Derived Nicotinamide Adenine Dinucleotide Phosphate Oxidase in Experimental Ischemic Stroke SO ANNALS OF NEUROLOGY LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; BRAIN-BARRIER PERMEABILITY; NADPH OXIDASE; REPERFUSION INJURY; MILD HYPOTHERMIA; IN-VIVO; APOCYNIN; MICE; RATS; IRRADIATION AB Objective: Reperfusion after stroke leads to infiltration of inflammatory cells into the ischemic brain. Nicotinamide adenine dinucleotide phosphate oxidase (NOX2) is a major enzyme system that generates superoxide in immune cells. We studied the effect of NOX2 derived from the immune cells in the brain and in blood cells in experimental stroke. Methods: To establish whether NOX2 plays a role in brain ischemia, strokes were created in mice, then mice were treated with the NOX2 inhibitor apocynin or vehicle and compared to mice deficient in NOX2's gp91 subunit and their wild-type littermates. To determine whether NOX2 in circulating cells versus brain resident cells contribute to ischemic injury, bone marrow chimeras were generated by transplanting bone marrow from wild-type or NOX2-deficient mice into NOX2 or wild-type hosts, respectively. Results: Apocynin and NOX2 deletion both significantly reduced infarct size, blood-brain barrier disruption, and hemorrhagic transformation of the infarcts, compared to untreated wild-type controls. This was associated with decreased matrix metalloproteinase 9 expression and reduced loss of tight junction proteins. NOX2-deficient mice receiving wild-type marrow had better outcomes compared to the wild-type mice receiving wild-type marrow. Interestingly, wild-type mice receiving NOX2-deficient marrow had even smaller infarct sizes and less hemorrhage than NOX2-deficient mice receiving wild-type marrow. Interpretation: This indicates that NOX2, whether present in circulating cells or brain resident cells, contributes to ischemic brain injury and hemorrhage. However, NOX2 from the circulating cells contributed more to the exacerbation of stroke than that from brain resident cells. These data suggest the importance of targeting the peripheral immune system for treatment of stroke. ANN NEUROL 2011;70:606-615 C1 [Yenari, Midori A.] UCSF, Neurol VAMC 127, Dept Neurol, San Francisco, CA 94121 USA. [Tang, Xian N.; Zheng, Zhen; Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Tang, Xian N.; Giffard, Rona G.] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. RP Yenari, MA (reprint author), UCSF, Neurol VAMC 127, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA. EM yenari@alum.mit.edu FU NIH [NINDS R01 NS40516, NINDS P50 NS014543, NIGMS R01 GM 49831]; American Heart Association FX This work was supported by NIH grants NINDS R01 NS40516 (M.A.Y.), NINDS P50 NS014543 (M.A.Y., R. G. G.), and NIGMS R01 GM 49831 (R. G. G.), an American Heart Association Established Investigator Award (M.A.Y.). Grants to M.A.Y. were administered by the Northern California Institute for Research and Education and the Department of Veterans Affairs. NR 42 TC 30 Z9 32 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2011 VL 70 IS 4 BP 606 EP 615 DI 10.1002/ana.22476 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 839VD UT WOS:000296396700014 PM 22028221 ER PT J AU Morgenroth, DC Segal, AD Zelik, KE Czerniecki, JM Klute, GK Adamczyk, PG Orendurff, MS Hahn, ME Collins, SH Kuo, AD AF Morgenroth, David C. Segal, Ava D. Zelik, Karl E. Czerniecki, Joseph M. Klute, Glenn K. Adamczyk, Peter G. Orendurff, Michael S. Hahn, Michael E. Collins, Steven H. Kuo, Art D. TI The effect of prosthetic foot push-off on mechanical loading associated with knee osteoarthritis in lower extremity amputees SO GAIT & POSTURE LA English DT Article DE Prosthesis; Amputation; Osteoarthritis; Biomechanics; Rehabilitation ID TO-STEP TRANSITIONS; HUMAN WALKING; ADDUCTION MOMENT; INVERTED PENDULUM; STATIC ALIGNMENT; DISEASE SEVERITY; GAIT; ENERGY; PREVALENCE; ANKLE AB Lower extremity amputation not only limits mobility, but also increases the risk of knee osteoarthritis of the intact limb. Dynamic walking models of non-amputees suggest that pushing-off from the trailing limb can reduce collision forces on the leading limb. These collision forces may determine the peak knee external adduction moment (EAM), which has been linked to the development of knee OA in the general population. We therefore hypothesized that greater prosthetic push-off would lead to reduced loading and knee EAM of the intact limb in unilateral transtibial amputees. Seven unilateral transtibial amputees were studied during gait under three prosthetic foot conditions that were intended to vary push-off. Prosthetic foot-ankle push-off work, intact limb knee EAM and ground reaction impulses for both limbs during step-to-step transition were measured. Overall, trailing limb prosthetic push-off work was negatively correlated with leading intact limb 1st peak knee EAM (slope = .72 +/- .22; p = .011). Prosthetic push-off work and 1st peak intact knee EAM varied significantly with foot type. The prosthetic foot condition with the least push-off demonstrated the largest knee EAM, which was reduced by 26% with the prosthetic foot producing the most push-off. Trailing prosthetic limb push-off impulse was negatively correlated with leading intact limb loading impulse (slope = .34 +/- .14; p = .001), which may help explain how prosthetic limb push-off can affect intact limb loading. Prosthetic feet that perform more prosthetic push-off appear to be associated with a reduction in 1st peak intact knee EAM, and their use could potentially reduce die risk and burden of knee osteoarthritis in this population. Published by Elsevier B.V. C1 [Morgenroth, David C.; Segal, Ava D.; Czerniecki, Joseph M.; Klute, Glenn K.; Hahn, Michael E.] RR&D Ctr, Dept Vet Affairs, Seattle, WA USA. [Klute, Glenn K.; Hahn, Michael E.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Klute, Glenn K.] Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA. [Morgenroth, David C.; Czerniecki, Joseph M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Zelik, Karl E.; Adamczyk, Peter G.; Kuo, Art D.] Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USA. [Collins, Steven H.] Carnegie Mellon Univ, Dept Mech Engn, Pittsburgh, PA 15213 USA. [Adamczyk, Peter G.; Collins, Steven H.] Intelligent Prosthet Syst LLC, Ann Arbor, MI USA. [Orendurff, Michael S.] Texas Scottish Rite Hosp Children, Movement Sci Lab, Dallas, TX 75219 USA. RP Morgenroth, DC (reprint author), VA Puget Sound Hlth Care Syst, RCS 117,1660 S Columbian Way, Seattle, WA 98108 USA. EM dmorgen@u.washington.edu RI Kuo, Arthur/L-3359-2013; Adamczyk, Peter/P-5928-2014 OI Kuo, Arthur/0000-0001-5233-9709; Adamczyk, Peter/0000-0001-5374-7691; Morgenroth, David/0000-0002-0226-7775; Collins, Steve/0000-0002-3997-3374 FU U.S. Department of Veterans Affairs, Office of Research and Development Rehabilitation [A4372R, A4843C]; Rehabilitation Medicine Scientist Training Program; NIH [K12 HD001097] FX This work was supported by the U.S. Department of Veterans Affairs, Office of Research and Development Rehabilitation, R&D Program (Grants A4372R and A4843C). Additionally, Dr. Morgenroth's work was supported by the Rehabilitation Medicine Scientist Training Program and the NIH (grant K12 HD001097). Statistical analyses were performed by Jane B. Shofer, MS. Prosthetic adjustments were performed by Wayne Biggs, CPO. NR 34 TC 32 Z9 36 U1 5 U2 27 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD OCT PY 2011 VL 34 IS 4 BP 502 EP 507 DI 10.1016/j.gaitpost.2011.07.001 PG 6 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 841AQ UT WOS:000296484800011 PM 21803584 ER PT J AU Badanich, KA Doremus-Fitzwater, TL Mulholland, PJ Randall, PK Delpire, E Becker, HC AF Badanich, K. A. Doremus-Fitzwater, T. L. Mulholland, P. J. Randall, P. K. Delpire, E. Becker, H. C. TI NR2B-deficient mice are more sensitive to the locomotor stimulant and depressant effects of ethanol SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Alcohol; locomotor activity; loss of righting; mice; NMDA receptor ID D-ASPARTATE RECEPTORS; NMDA RECEPTOR; GLUTAMATE RECEPTORS; INSULAR CORTEX; NR2B SUBUNITS; C57BL/6J MICE; MOUSE-BRAIN; RAT; EXPRESSION; IFENPRODIL AB The NR2B subunit of N-methyl D-aspartate glutamate receptors influences pharmacological properties and confers greater sensitivity to the modulatory effects of ethanol. This study examined behavioral responses to acute ethanol in a conditional knockout mouse model that allowed for a delayed genetic deletion of the NR2B subunit to avoid mouse lethality. Mice lacking the NR2B gene (knockout) were produced by mating NR2B[f/f] mice with CAMKIIa-driven tTA transgenic mice and the tetO-CRE transgenic mice. Adult male and female offspring representing each of the resultant genotypes (knockout, CAM, CRE and wildtype mice) were tested for open-field locomotor activity following acute low- and high-dose ethanol challenge as well as loss of righting reflex. Findings indicate that male and female mice lacking the NR2B subunit exhibited greater overall activity in comparison to other genotypes during the baseline locomotor activity test. NR2B knockout mice exhibited an exaggerated stimulant response to 1.5 g/kg (i.p.) and an exaggerated depressant response to 3.0 g/kg (i.p.) ethanol challenge. In addition, NR2B knockout mice slept longer following a high dose of ethanol (4.0 g/kg, i.p.). To evaluate pharmacokinetics, clearance rates of ethanol (1.5, 4.0 g/kg, i.p.) were measured and showed that female NR2B knockouts had a faster rate of metabolism only at the higher ethanol dose. Western blot analyses confirmed significant reduction in NR2B expression in the forebrain of knockout mice. Collectively, these data indicate that the NR2B subunit of the N-methyl D-aspartate glutamate receptor is involved in regulating low-dose stimulant effects of ethanol and the depressant/hypnotic effects of ethanol. C1 [Badanich, K. A.; Doremus-Fitzwater, T. L.; Mulholland, P. J.; Randall, P. K.; Becker, H. C.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston Alcohol Res Ctr, Charleston, SC 29425 USA. [Delpire, E.] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37212 USA. [Becker, H. C.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Becker, HC (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston Alcohol Res Ctr, 67 President St,IOP 456N, Charleston, SC 29425 USA. EM beckerh@musc.edu FU NIAAA [AA13514, AA14095] FX This work was supported by NIAAA grants AA13514 to E.D. and AA14095 to H.C.B. The authors would like to thank Dr John J. Woodward for insightful comments during the preparation of this manuscript. A special thanks to Kay Fernandez, Josh Sanchez, Michelle Cunningham and Catherine Hindman for their technical assistance. NR 55 TC 18 Z9 18 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD OCT PY 2011 VL 10 IS 7 BP 805 EP 816 DI 10.1111/j.1601-183X.2011.00720.x PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 837WD UT WOS:000296238100013 PM 21762461 ER PT J AU Wenger, NS Roth, CP Martin, D Nickels, L Beckman, R Kamberg, C Mach, J Ganz, DA AF Wenger, Neil S. Roth, Carol P. Martin, David Nickels, Lorraine Beckman, Robin Kamberg, Caren Mach, John Ganz, David A. TI Quality of Care Provided in a Special Needs Plan Using a Nurse Care Manager Model SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE special needs plan; quality of care; vulnerable elders; nurse care manager ID VULNERABLE OLDER PATIENTS; HOME RESIDENTS; EVERCARE; DEMENTIA; SERVICES AB OBJECTIVES: To comprehensively evaluate the quality of care provided in special needs plans (SNPs; Medicare Advantage plans that aim to provide specialized care for complex older adults) and specifically the nurse care management model in the community setting. DESIGN: We adapted 107 process-of-care quality measures across 12 conditions from the Assessing Care of Vulnerable Elders set to obtain a clinically detailed evaluation of the quality of care received by complex older enrollees in a dual eligible Evercare SNP. We abstracted 13 months of primary care medical records to delineate quality of care provided by physicians and whether there was value added from the nurse care manager model. SETTING: Dual eligible Evercare SNP located in central Florida. PARTICIPANTS: Two-hundred thirty-one vulnerable older enrollees in the SNP who had complex disease. RESULTS: Based on physician medical records alone, the 231 high-risk participants (mean age 77, 67% women) received recommended care for 53% of 5,569 evaluated clinical circumstances, ranging from 12% for end-of-life care to 78% for diabetes mellitus. In fewer than 40% of these clinical circumstances was recommended care provided for dementia, falls, and urinary incontinence. In a second analysis accounting for care provided by both the Evercare nurse and the physician, recommended care was provided to patients in 69% of the 5,684 evaluated clinical circumstances. CONCLUSION: Comprehensive quality measurement applied to vulnerable older adults enrolled in one mature SNP showed that the Evercare nurse model addresses important deficits in physician care for geriatric conditions. Such measurement should be applied to other SNP models and to compare SNP care with that for complex, older, fee-for-service Medicare cohorts. J Am Geriatr Soc 59:1810-1822, 2011. C1 [Wenger, Neil S.] Univ Calif Los Angeles, Div GIM, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Wenger, Neil S.; Roth, Carol P.; Beckman, Robin; Ganz, David A.] RAND Hlth, Santa Monica, CA USA. [Kamberg, Caren] RAND Hlth, Arlington, VA USA. [Martin, David; Nickels, Lorraine] UnitedHlth Grp, Minnetonka, MN USA. [Mach, John] Univita Hlth, Eden Prairie, MN USA. [Ganz, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Wenger, NS (reprint author), Univ Calif Los Angeles, Div GIM, David Geffen Sch Med, 911 Broxton Plaza 309, Los Angeles, CA 90024 USA. EM nwenger@mednet.ucla.edu FU UnitedHealthcare; United-Health Group FX Conflict of Interest: For NW, CR, RB, CK, and DG, UnitedHealthcare funded the project. DM and LN are employed by UnitedHealthcare and retain stock. JM was an employee of UnitedHeathcare at the time of the study and still owns stock.; This project was supported by a contract from United-Health Group to RAND. NR 21 TC 6 Z9 6 U1 0 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 OCT PY 2011 VL 59 IS 10 BP 1810 EP 1822 DI 10.1111/j.1532-5415.2011.03599.x PG 13 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 840OE UT WOS:000296449300005 PM 22091494 ER PT J AU Yanover, C Jain, N Pierce, G Howard, TE Sauna, ZE AF Yanover, Chen Jain, Nisha Pierce, Glenn Howard, Tom E. Sauna, Zuben E. TI Pharmacogenetics and the immunogenicity of protein therapeutics SO NATURE BIOTECHNOLOGY LA English DT Letter ID FACTOR-VIII; RISK-FACTORS; IMMUNE-RESPONSES; INHIBITORS; PREVENTION; HEMOPHILIA; PREDICTION C1 [Yanover, Chen] Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98104 USA. [Jain, Nisha] US FDA, Clin Review Branch, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Pierce, Glenn] Biogen Idec Hemophilia, Waltham, MA USA. [Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. [Sauna, Zuben E.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Yanover, C (reprint author), Fred Hutchinson Canc Res Ctr, Program Computat Biol, 1124 Columbia St, Seattle, WA 98104 USA. EM Zuben.Sauna@fda.hhs.gov RI Yanover, Chen/A-3754-2012 OI Yanover, Chen/0000-0003-3663-4286 NR 20 TC 13 Z9 13 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD OCT PY 2011 VL 29 IS 10 BP 870 EP 873 DI 10.1038/nbt.2002 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 838FQ UT WOS:000296273000009 PM 21997623 ER PT J AU Bartzokis, G Lu, PH Amar, CP Raven, EP Detore, NR Altshuler, LL Mintz, J Ventura, J Casaus, LR Luo, JS Subotnik, KL Nuechterlein, KH AF Bartzokis, George Lu, Po H. Amar, Chetan P. Raven, Erika P. Detore, Nicole R. Altshuler, Lori L. Mintz, Jim Ventura, Joseph Casaus, Laurie R. Luo, John S. Subotnik, Kenneth L. Nuechterlein, Keith H. TI Long acting injection versus oral risperidone in first-episode schizophrenia: Differential impact on white matter myelination trajectory SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Antipsychotic; Medication; Dopamine; Second generation; Atypical; Myelin; White matter; Gray matter; Oligodendrocyte; Development; Aging ID SCHIZOAFFECTIVE DISORDER; TREATMENT RESPONSE; INTRACORTICAL MYELINATION; ATYPICAL ANTIPSYCHOTICS; PREFRONTAL CORTEX; 1ST EPISODE; BRAIN; ABNORMALITIES; CHOLESTEROL; PREDICTORS AB Context: Imaging and post-mortem studies provide converging evidence that subjects with schizophrenia (SZ) have a dysregulated trajectory of frontal lobe myelination. Prior MRI studies suggested that early in treatment of SZ, antipsychotic medications initially increase frontal lobe white matter (WM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of WM decline associated with chronic disease may be due to medication non-adherence, it may be modifiable by long acting injection (LAI) formulations. Objectives: Examine the impact of antipsychotic formulation on the myelination trajectory during a randomized six-month trial of LAI risperidone (RLAI) versus oral risperidone (RisO) in first-episode SZ subjects. Design: Two groups of SZ subjects (RLAI, N = 11; and RisO, N = 13) that were matched in pre-randomization oral medication exposure and 14 healthy controls (HCs) were prospectively examined. Frontal lobe WM volume was estimated using inversion recovery (IR) MRI images. A brief neuropsychological battery that focused on reaction times was performed at the end of the study. Main outcome measure: WM volume change scores. Results: WM volume remained stable in the RLAI and decreased significantly in the RisO groups resulting in a significant differential treatment effect, while the HC had a WM change intermediate and not significantly different from the two SZ groups. WM increase was associated with faster reaction times in tests involving frontal lobe function. Conclusions: The results suggest that RLAI may improve the trajectory of myelination in first-episode patients and have a beneficial impact on cognitive performance. Better adherence provided by LAI may underlie the modified trajectory of myelin development. In vivo MRI biomarkers of myelination can help clarify mechanisms of action of treatment interventions. Published by Elsevier B.V. C1 [Bartzokis, George; Amar, Chetan P.; Raven, Erika P.; Detore, Nicole R.; Altshuler, Lori L.; Ventura, Joseph; Casaus, Laurie R.; Luo, John S.; Subotnik, Kenneth L.; Nuechterlein, Keith H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Div Brain Mapping, Dept Neurol,Lab Neuroimaging, Los Angeles, CA 90095 USA. [Bartzokis, George; Amar, Chetan P.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Lu, Po H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mintz, Jim] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 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 [MH 0266029, AG027342, MH51928, MH6357, MH037705, P50 MH066286]; Ortho-McNeil Janssen Scientific Affairs, LLC.; Department of Veterans Affairs; Janssen Pharmaceutical Inc. FX Funding for this study was supported in part by NIH grants (MH 0266029; AG027342; MH51928; MH6357; MH037705; P50 MH066286) and two investigator-initiated grants from Ortho-McNeil Janssen Scientific Affairs, LLC.; and the Department of Veterans Affairs. The NIH, Janssen Pharmaceutical Inc., and the Department of Veterans Affairs 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.; George Bartzokis and Keith Nuechterlein have received funding from Janssen Pharmaceutical Inc. George Bartzokis has consulted for Janssen Pharmaceutical Inc. NR 53 TC 34 Z9 36 U1 4 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2011 VL 132 IS 1 BP 35 EP 41 DI 10.1016/j.schres.2011.06.029 PG 7 WC Psychiatry SC Psychiatry GA 833VJ UT WOS:000295912700006 PM 21767934 ER PT J AU Piette, EW Werth, VP AF Piette, Evan W. Werth, Victoria P. TI Dapsone in the Management of Autoimmune Bullous Diseases SO DERMATOLOGIC CLINICS LA English DT Article DE Dapsone; Autoimmune bullous disease; Review ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; DERMATITIS-HERPETIFORMIS; ACQUISITA; PEMPHIGUS; DIAGNOSIS; ERUPTION; COLCHICINE; DERMATOSIS; THERAPY; WOMAN AB Dapsone is used in the treatment of autoimmune bullous diseases (AIBD), a group of disorders resulting from autoimmunity directed against basement membrane and/or intercellular adhesion molecules on cutaneous and mucosal surfaces. This review summarizes the limited published data evaluating dapsone as a therapy for AIBD. C1 [Piette, Evan W.; Werth, Victoria P.] Perelman Ctr Adv Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Div Dermatol, Philadelphia, PA USA. RP Werth, VP (reprint author), Perelman Ctr Adv Med, Dept Dermatol, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU National Institutes of Health [NIH K24-AR 02207] FX National Institutes of Health, including NIH K24-AR 02207 (V.P.W.). NR 41 TC 7 Z9 7 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD OCT PY 2011 VL 29 IS 4 BP 561 EP + DI 10.1016/j.det.2011.06.018 PG 5 WC Dermatology SC Dermatology GA 831UB UT WOS:000295755500005 PM 21924998 ER PT J AU Murrell, DF Werth, VP Segall, J Zrnchik, W Stuart, M Sirois, D AF Murrell, Dedee F. Werth, Victoria P. Segall, Janet Zrnchik, Will Stuart, Molly Sirois, David TI The International Pemphigus and Pemphigoid Foundation SO DERMATOLOGIC CLINICS LA English DT Article DE International Pemphigus Pemphigoid Foundation; Pemphigus; Pemphigoid; Pemphigus vulgaris AB The International Pemphigus Pemphigoid Foundation (IPFF) was founded in 1997. The IPPF lists more than 4500 members. The IPPF provides peer health coaches to aid patients in the navigation of the health care system and recommends dermatologists and other specialists in their area who are experts in autoimmune bullous disease. The IPPF hosts the largest worldwide registry of pemphigus/pemphigoid patients with biospecimen collection opportunities are planned. Twice a year the IPPF hosts formal meetings with invited speakers. C1 [Segall, Janet; Zrnchik, Will; Stuart, Molly; Sirois, David] Int Pemphigus Pemphigoid Fdn, Sacramento, CA 95825 USA. [Sirois, David] NYU, Dept Dent, New York, NY 10022 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Div Dermatol, Philadelphia, PA USA. [Werth, Victoria P.] Perelman Ctr Adv Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Murrell, Dedee F.] Univ New S Wales, St George Hosp, Dept Dermatol, Sydney, NSW 2217, Australia. RP Sirois, D (reprint author), Int Pemphigus Pemphigoid Fdn, 2701 Cottage Way 16, Sacramento, CA 95825 USA. EM david.sirois@nyu.edu FU NIAMS NIH HHS [K24 AR002207] NR 3 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD OCT PY 2011 VL 29 IS 4 BP 655 EP + DI 10.1016/j.det.2011.06.019 PG 5 WC Dermatology SC Dermatology GA 831UB UT WOS:000295755500020 PM 21925013 ER PT J AU Amati, F Dube, JJ Alvarez-Carnero, E Edreira, MM Chomentowski, P Coen, PM Switzer, GE Bickel, PE Stefanovic-Racic, M Toledo, FGS Goodpaster, BH AF Amati, Francesca Dube, John J. Alvarez-Carnero, Elvis Edreira, Martin M. Chomentowski, Peter Coen, Paul M. Switzer, Galen E. Bickel, Perry E. Stefanovic-Racic, Maja Toledo, Frederico G. S. Goodpaster, Bret H. TI Skeletal Muscle Triglycerides, Diacylglycerols, and Ceramides in Insulin Resistance Another Paradox in Endurance-Trained Athletes? SO DIABETES LA English DT Article ID INTRAMUSCULAR LIPID-METABOLISM; STEAROYL-COA DESATURASE-1; SPHINGOLIPID METABOLISM; OBESE HUMANS; WEIGHT-LOSS; EXERCISE; PROTEIN; DIET; SPHINGOSINE-1-PHOSPHATE; SENSITIVITY AB OBJECTIVE-Chronic exercise and obesity both increase intra-myocellular triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We hypothesized that chronically exercise-trained muscle would be characterized by lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs and would account for its higher insulin sensitivity. We also hypothesized that the expression of key skeletal muscle proteins involved in lipid droplet hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be associated with the lipotoxic phenotype. RESEARCH DESIGN AND METHODS-A total of 14 normal-weight, endurance-trained athletes (NWA group) and 7 normal-weight sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied. Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and protein expression were measured in muscle biopsies. RESULTS-DAG content in the NWA group was approximately twofold higher than in the OBS group and similar to 50% higher than in the NWS group, corresponding to higher insulin sensitivity. While certain DAG moieties clearly were associated with better insulin sensitivity, other species were not. Ceramide content was higher in insulin-resistant obese muscle. The expression of OXPAT/perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturase protein was higher in the NWA group, corresponding to a higher mitochondrial content, proportion of type 1 myocytes, DAGs, and insulin sensitivity. CONCLUSIONS-Total myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. Our data also provide additional evidence in humans linking ceramides to insulin resistance. Finally, this study provides novel evidence supporting a role for specific skeletal muscle proteins involved in intramyocellular lipids, mitochondrial oxidative capacity, and insulin resistance. Diabetes 60:2588-2597, 2011 C1 [Amati, Francesca; Dube, John J.; Alvarez-Carnero, Elvis; Chomentowski, Peter; Coen, Paul M.; Stefanovic-Racic, Maja; Toledo, Frederico G. S.; Goodpaster, Bret H.] Univ Pittsburgh, Sch Med, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA 15260 USA. [Amati, Francesca] Univ Lausanne, Dept Physiol, Sch Biol & Med, Lausanne, Switzerland. [Edreira, Martin M.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. [Switzer, Galen E.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Switzer, Galen E.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Switzer, Galen E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Bickel, Perry E.] Univ Texas Hlth Sci Ctr Houston, Ctr Metab & Degenerat Dis, Brown Fdn Inst Mol Med, Houston, TX USA. [Bickel, Perry E.] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Div Endocrinol Diabet & Metab, Houston, TX USA. RP Goodpaster, BH (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA 15260 USA. EM bgood@pitt.edu RI Toledo, Frederico/G-9071-2013; Carnero, Elvis/A-5815-2014 OI Carnero, Elvis/0000-0003-0442-4217; Alvarez Carnero, Elvis/0000-0002-7464-228X; Amati, Francesca/0000-0002-1731-0262; Coen, Paul/0000-0002-2805-2115 FU National Institutes of Health (NIH) [R01-AG20128, R01-DK068046]; American College of Sports Medicine Foundation; University of Pittsburgh; NIH/National Center for Research Resources/Clinical and Translational Science [UL1 RR024153]; University of Pittsburgh Obesity and Nutrition Research Center [1P30DK46204] FX This study was supported by National Institutes of Health (NIH) Grants (R01-AG20128 to B.H.G. and R01-DK068046 to P.E.B.), funding from the American College of Sports Medicine Foundation (to F.A.), University of Pittsburgh Student and Faculty Grants (to B.H.G. and F.A.), an NIH/National Center for Research Resources/Clinical and Translational Science Award (UL1 RR024153), and University of Pittsburgh Obesity and Nutrition Research Center Grant 1P30DK46204. NR 53 TC 145 Z9 150 U1 3 U2 38 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2011 VL 60 IS 10 BP 2588 EP 2597 DI 10.2337/db10-1221 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834XV UT WOS:000295998700018 PM 21873552 ER PT J AU Park, BJ Pappas, PG Wannemuehler, KA Alexander, BD Anaissie, EJ Andes, DR Baddley, JW Brown, JM Brumble, LM Freifeld, AG Hadley, S Herwaldt, L Ito, JI Kauffman, CA Lyon, GM Marr, KA Morrison, VA Papanicolaou, G Patterson, TF Perl, TM Schuster, MG Walker, R Wingard, JR Walsh, TJ Kontoyiannis, DP AF Park, Benjamin J. Pappas, Peter G. Wannemuehler, Kathleen A. Alexander, Barbara D. Anaissie, Elias J. Andes, David R. Baddley, John W. Brown, Janice M. Brumble, Lisa M. Freifeld, Alison G. Hadley, Susan Herwaldt, Loreen Ito, James I. Kauffman, Carol A. Lyon, G. Marshall Marr, Kieren A. Morrison, Vicki A. Papanicolaou, Genovefa Patterson, Thomas F. Perl, Trish M. Schuster, Mindy G. Walker, Randall Wingard, John R. Walsh, Thomas J. Kontoyiannis, Dimitrios P. TI Invasive Non-Aspergillus Mold Infections in Transplant Recipients, United States, 2001-2006 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID HEMATOPOIETIC STEM-CELL; CARE CANCER CENTER; SURVEILLANCE NETWORK TRANSNET; FUNGAL-INFECTIONS; HEMATOLOGIC MALIGNANCIES; BREAKTHROUGH ZYGOMYCOSIS; SCEDOSPORIUM-PROLIFICANS; RECEIVING VORICONAZOLE; ANTIFUNGAL THERAPY; EPIDEMIOLOGY AB Recent reports describe increasing incidence of non-Aspergillus mold infections in hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients. To investigate the epidemiology of infections with Mucorales, Fusarium spp., and Scedosporium spp. molds, we analyzed data from the Transplant-Associated Infection Surveillance Network, 23 transplant centers that conducted prospective surveillance for invasive fungal infections during 2001-2006. We identified 169 infections (105 Mucorales, 37 Fusarium spp., and 27 Scedosporium spp.) in 169 patients; 124 (73.4%) were in HCT recipients, and 45 (26.6%) were in SOT recipients. The crude 90-day mortality rate was 56.6%. The 12-month mucormycosis cumulative incidence was 0.29% for HCT and 0.07% for SOT. Mucormycosis incidence among HCT recipients varied widely, from 0.08% to 0.69%, with higher incidence in cohorts receiving transplants during 2003 and 2004. Non-Aspergillus mold infections continue to be associated with high mortality rates. The incidence of mucormycosis in HOT recipients increased substantially during the surveillance period. C1 [Park, Benjamin J.] Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA 30333 USA. [Pappas, Peter G.; Baddley, John W.] Univ Alabama, Med Ctr, Birmingham, AL 35294 USA. [Alexander, Barbara D.] Duke Univ, Med Ctr, Durham, NC USA. [Anaissie, Elias J.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Andes, David R.] Univ Wisconsin, Madison, WI USA. [Brown, Janice M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Brumble, Lisa M.] Mayo Clin, Jacksonville, FL 32224 USA. [Freifeld, Alison G.] Univ Nebraska Med Ctr, Omaha, NE USA. [Hadley, Susan] Tufts Med Ctr, Boston, MA USA. [Herwaldt, Loreen] Univ Iowa Hosp, Iowa City, IA USA. [Ito, James I.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Kauffman, Carol A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Kauffman, Carol A.] Vet Affairs Ann Arbor Healthcare Syst Med, Ann Arbor, MI USA. [Lyon, G. Marshall] Emory Univ, Sch Med, Atlanta, GA USA. [Marr, Kieren A.; Perl, Trish M.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Marr, Kieren A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Morrison, Vicki A.] Univ Minnesota, Minneapolis, MN USA. [Morrison, Vicki A.] Vet Affairs Med Ctr, Minneapolis, MN USA. [Papanicolaou, Genovefa] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Patterson, Thomas F.] S Texas Vet Healthcare Syst, San Antonio, TX USA. [Schuster, Mindy G.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Walker, Randall] Mayo Clin, Rochester, MN USA. [Wingard, John R.] Univ Florida, Gainesville, FL USA. [Walsh, Thomas J.] NIH, Bethesda, MD 20892 USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Park, BJ (reprint author), Ctr Dis Control & Prevent, Mycot Dis Branch, 1600 Clifton Rd NE,Mailstop C09, Atlanta, GA 30333 USA. EM bpark1@cdc.gov OI Papanicolaou, Genovefa/0000-0002-2891-079X; Patterson, Thomas /0000-0002-9513-7127 FU Centers for Disease Control and Prevention [5U01CI000286-05]; Merck Co., Inc.; Astellas U.S., Inc.; Pfizer, Inc.; Schering-Plough Research Institute; Enzon Pharmaceuticals, Inc. FX This study was supported through Centers for Disease Control and Prevention Grant 5U01CI000286-05 and grants from Merck & Co., Inc.; Astellas U.S., Inc.; Pfizer, Inc.; Schering-Plough Research Institute; and Enzon Pharmaceuticals, Inc. NR 35 TC 74 Z9 74 U1 0 U2 8 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD OCT PY 2011 VL 17 IS 10 BP 1855 EP 1864 DI 10.3201/eid1710.110087 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 833PL UT WOS:000295897300009 PM 22000355 ER PT J AU Wasterlain, C Baldwin, R Naylor, DE Thompson, KW Suchomelova, L Niquet, J AF Wasterlain, ClaudeG. Baldwin, Roger Naylor, David E. Thompson, Kerry W. Suchomelova, Lucie Niquet, Jerome TI Rational polytherapy in the treatment of acute seizures and status epilepticus SO EPILEPSIA LA English DT Article DE Status epilepticus; Acute seizures; Cholinergic seizures; Drug toxicity; GABA(A) receptors; NMDA receptors; Neuronal injury; Monotherapy ID GABA(A) RECEPTORS; TRAFFICKING AB We used a model of severe cholinergic status epilepticus (SE) to study polytherapy aimed at reversing the effects of seizure-induced loss of synaptic GABA(A) receptors and seizure-induced gain of synaptic NMDA receptors. Combinations of a benzodiazepine with ketamine and valproate, or with ketamine and brivaracetam, were more effective and less toxic than benzodiazepine monotherapy in this model of SE. C1 [Wasterlain, ClaudeG.; Baldwin, Roger; Naylor, David E.; Thompson, Kerry W.; Suchomelova, Lucie; Niquet, Jerome] VA Greater Angeles Hlth Care Syst, Epilepsy Res Lab, Los Angeles, CA USA. [Wasterlain, ClaudeG.; Naylor, David E.; Thompson, Kerry W.; Suchomelova, Lucie; Niquet, Jerome] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Wasterlain, ClaudeG.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Wasterlain, C (reprint author), UCLA Geffen Sch Med, Dept Neurol, W LA VA Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM wasterla@ucla.edu FU Research Service of VHA; NINDS [NS13515, NS 05974]; James and Debbie Cho Foundation FX Supported by the Research Service of VHA, by grants NS13515 and NS 05974 from NINDS, and by the James and Debbie Cho Foundation. NR 5 TC 23 Z9 23 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2011 VL 52 SU 8 SI SI BP 70 EP 71 DI 10.1111/j.1528-1167.2011.03243.x PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 835VR UT WOS:000296065200023 PM 21967369 ER PT J AU van Rooyen, DM Larter, CZ Haigh, WG Yeh, MM Ioannou, G Kuver, R Lee, SP Teoh, NC Farrell, GC AF van Rooyen, Derrick M. Larter, Claire Z. Haigh, W. Geoffrey Yeh, Matthew M. Ioannou, George Kuver, Rahul Lee, Sum P. Teoh, Narci C. Farrell, Geoffrey C. TI Hepatic Free Cholesterol Accumulates in Obese, Diabetic Mice and Causes Nonalcoholic Steatohepatitis SO GASTROENTEROLOGY LA English DT Article DE Lipotoxicity; LRH-1; Bsep; Liver Damage ID FATTY LIVER-DISEASE; TRANSCRIPTIONAL REGULATION; MESSENGER-RNA; EXPRESSION; HEPATOCYTES; ASSOCIATION; SUPPRESSION; RESISTANCE; ROLES; RAT AB BACKGROUND & AIMS: Type 2 diabetes and nonalcoholic steatohepatitis (NASH) are associated with insulin resistance and disordered cholesterol homeostasis. We investigated the basis for hepatic cholesterol accumulation with insulin resistance and its relevance to the pathogenesis of NASH. METHODS: Alms1 mutant (foz/foz) and wild-type NOD. B10 mice were fed high-fat diets that contained varying percentages of cholesterol; hepatic lipid pools and pathways of cholesterol turnover were determined. Hepatocytes were exposed to insulin concentrations that circulate in diabetic foz/foz mice. RESULTS: Hepatic cholesterol accumulation was attributed to upregulation of low-density lipoprotein receptor via activation of sterol regulatory element binding protein 2 (SREBP-2), reduced biotransformation to bile acids, and suppression of canalicular pathways for cholesterol and bile acid excretion in bile. Exposing primary hepatocytes to concentrations of insulin that circulate in diabetic Alms1 mice replicated the increases in SREBP-2 and low-density lipoprotein receptor and suppression of bile salt export pump. Removing cholesterol from diet prevented hepatic accumulation of free cholesterol and NASH; increasing dietary cholesterol levels exacerbated hepatic accumulation of free cholesterol, hepatocyte injury or apoptosis, macrophage recruitment, and liver fibrosis. CONCLUSIONS: In obese, diabetic mice, hyperinsulinemia alters nuclear transcriptional regulators of cholesterol homeostasis, leading to hepatic accumulation of free cholesterol; the resulting cytotoxicity mediates transition of steatosis to NASH. C1 [Farrell, Geoffrey C.] Canberra Hosp, Gastroenterol & Hepatol Unit, Liver Res Grp, ANU Med Sch, Garran, ACT 2605, Australia. [Haigh, W. Geoffrey; Kuver, Rahul; Lee, Sum P.] Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA. [Yeh, Matthew M.] Univ Washington, Med Ctr, Dept Med, Seattle, WA 98195 USA. [Yeh, Matthew M.] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. [Ioannou, George] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Farrell, GC (reprint author), Canberra Hosp, Gastroenterol & Hepatol Unit, Liver Res Grp, ANU Med Sch, Yamba Dr, Garran, ACT 2605, Australia. EM geoff.farrell@anu.edu.au FU Australian National Health and Medical Research Council (NHMRC) [418101, 585411]; NHMRC [585539]; National Institutes of Health [RO1CA114403] FX Supported by project grants 418101 and 585411 of the Australian National Health and Medical Research Council (NHMRC), NHMRC scholarship 585539, and National Institutes of Health grant RO1CA114403. NR 29 TC 100 Z9 100 U1 3 U2 18 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2011 VL 141 IS 4 BP 1393 EP U850 DI 10.1053/j.gastro.2011.06.040 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829OQ UT WOS:000295593700046 PM 21703998 ER PT J AU Chavalitdhamrong, D Jensen, DM Kovacs, TOG Jutabha, R Dulai, G Ohning, G Machicado, GA AF Chavalitdhamrong, Disaya Jensen, Dennis M. Kovacs, Thomas O. G. Jutabha, Rome Dulai, Gareth Ohning, Gordon Machicado, Gustavo A. TI Ischemic colitis as a cause of severe hematochezia: risk factors and outcomes compared with other colon diagnoses SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID URGENT COLONOSCOPY; SPECTRUM AB Background: Risk factors and outcomes of severe hematochezia from ischemic colitis compared with other colonic diagnoses have not been well studied. Objective: Our purposes were (1) to compare demographics and outcomes of patients hospitalized with severe hematochezia from ischemic colitis compared with other colonic diagnoses, (2) to compare inpatient and outpatient start of bleeding from ischemic colitis, and (3) to describe potential risk factors. Design: Prospective cohort study. Setting: Tertiary referral academic centers. Patients: Patients referred for gastroenterology consultation for severe hematochezia. Interventions: Colonoscopic therapy was provided as indicated. Main Outcome Measurements: Rebleeding, surgery, and length of hospital stay after colonoscopy. Results: Of 550 patients in the past 12 years with severe hematochezia from colonic sources, the cause in 65 patients (11.8%) was ischemia. Ischemic colitis was found more often in females, in patients taking anticoagulant agents, in patients with severe lung disease, those with higher creatinine levels, those with higher glucose levels, and those with more fresh frozen plasma transfusions. Five patients with focal lesions had colonoscopic hemostasis. Major 30-day outcomes of ischemic colitis patients were significantly worse than patients with other colonic diagnoses. Patients with inpatient (vs outpatient) ischemic colitis had significantly more and more severe comorbidities at baseline and significantly higher rates of rebleeding, surgery, and more days spent in hospital and in the intensive care unit. Limitations: Two-center study. Conclusions: Major 30-day outcomes in ischemic colitis patients were significantly worse than in patients with other colonic diagnoses. Comparing outpatient and inpatient start of ischemic colitis, inpatients had significantly worse outcomes. (Gastrointest Endosc 2011;74:852-7.) C1 [Chavalitdhamrong, Disaya; Jensen, Dennis M.; Kovacs, Thomas O. G.; Jutabha, Rome; Dulai, Gareth; Ohning, Gordon; Machicado, Gustavo A.] Greater Los Angeles VA Healthcare Ctr, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. [Chavalitdhamrong, Disaya; Jensen, Dennis M.; Kovacs, Thomas O. G.; Jutabha, Rome; Dulai, Gareth; Ohning, Gordon; Machicado, Gustavo A.] CURE, Hemostasis Res Unit, Los Angeles, CA USA. [Jensen, Dennis M.; Kovacs, Thomas O. G.; Jutabha, Rome; Machicado, Gustavo A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Jensen, Dennis M.; Kovacs, Thomas O. G.; Jutabha, Rome; Machicado, Gustavo A.] Univ Calif Los Angeles, Div Digest Dis, Ronald Reagan Med Ctr, Los Angeles, CA 90095 USA. [Jensen, Dennis M.; Kovacs, Thomas O. G.; Dulai, Gareth; Ohning, Gordon; Machicado, Gustavo A.] Greater Los Angeles VA Healthcare Ctr, GI Hepatol Sect, Los Angeles, CA 90073 USA. RP Jensen, DM (reprint author), Greater Los Angeles VA Healthcare Ctr, CURE Digest Dis Res Ctr, Bldg 115,Room 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIH [K24 DK002650]; CURE Digestive Diseases Research Center [P30 DK041301] FX All authors disclosed no financial relationships relevant to this publication. This study was partially supported by research funds from an NIH grant (K24 DK002650) and CURE Digestive Diseases Research Center Human Studies Core grant (P30 DK041301). NR 14 TC 11 Z9 11 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2011 VL 74 IS 4 BP 852 EP 857 DI 10.1016/j.gie.2011.05.039 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 834ME UT WOS:000295963900017 PM 21839438 ER PT J AU Day, LW Kwon, A Inadomi, JM Walter, LC Somsouk, M AF Day, Lukejohn W. Kwon, Annette Inadomi, John M. Walter, Louise C. Somsouk, Ma TI Adverse events in older patients undergoing colonoscopy: a systematic review and meta-analysis SO GASTROINTESTINAL ENDOSCOPY LA English DT Review ID COLORECTAL-CANCER; OUTPATIENT COLONOSCOPY; SCREENING COLONOSCOPY; CLINICAL-PRACTICE; DIAGNOSTIC YIELD; GI ENDOSCOPY; RISK-FACTORS; COMPLICATIONS; PERFORATION; POPULATION AB Background: Studies suggest that advancing age is an independent risk factor for experiencing adverse events during colonoscopy. Yet many of these studies are limited by small sample sizes and/or marked variation in reported outcomes. Objective: To determine the incidence rates for specific adverse events in elderly patients undergoing colonoscopy and calculate incidence rate ratios for selected comparison groups. Setting and Patients: Elderly patients undergoing colonoscopy. Design: Systematic review and meta-analysis. Main Outcome Measurements: Perforation, bleeding, cardiovascular (CV)/pulmonary complications, and mortality. Results: Our literature search yielded 3328 articles, of which 20 studies met our inclusion criteria. Pooled incidence rates for adverse events (per 1000 colonoscopies) in patients 65 years of age and older were 26.0 (95% CI, 25.0-27.0) for cumulative GI adverse events, 1.0 (95% CI, 0.9-1.5) for perforation, 6.3 (95% CI, 5.7-7.0) for GI bleeding, 19.1 (95% CI, 18.0-20.3) for CV/pulmonary complications, and 1.0 (95% CI, 0.7-2.2) for mortality. Among octogenarians, adverse events (per 1000 colonoscopies) were as follows: cumulative GI adverse event rate of 34.9 (95% CI, 31.9-38.0), perforation rate of 1.5 (95% CI, 1.1-1.9), GI bleeding rate of 2.4 (95% CI, 1.1-4.6), CV/pulmonary complication rate of 28.9 (95% CI, 26.2-31.8), and mortality rate of 0.5 (95% CI, 0.06-1.9). Patients 80 years of age and older experienced higher rates of cumulative GI adverse events (incidence rate ratio 1.7; 95% CI, 1.5-1.9) and had a greater risk of perforation (incidence rate ratio 1.6, 95% CI, 1.2-2.1) compared with younger patients (younger than 80 years of age). There was an increased trend toward higher rates of GI bleeding and CV/pulmonary complications in octogenarians but neither was statistically significant. Limitations: Heterogeneity of studies included and not all complications related to colonoscopy were captured. Conclusions: Elderly patients, especially octogenarians, appear to have a higher risk of complications during and after colonoscopy. These data should inform clinical decision making, the consent process, public health policy, and comparative effectiveness analyses. (Gastrointest Endosc 2011;74:885-96.) C1 [Day, Lukejohn W.; Somsouk, Ma] San Francisco Gen Hosp, Div Gastroenterol, San Francisco, CA 94110 USA. [Day, Lukejohn W.; Somsouk, Ma] Univ Calif San Francisco, Dept Med, GI Hlth Outcomes, Policy & Econ HOPE Res Program, San Francisco, CA USA. [Kwon, Annette] Calif Pacific Med Ctr, Dept Gastroenterol, San Francisco, CA USA. [Inadomi, John M.] Univ Washington, Dept Med, Div Gastroenterol & Hepatol, Seattle, WA USA. [Walter, Louise C.] San Francisco VA Med Ctr, Div Geriatr, 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 RI Inadomi, John/A-6221-2014 OI Inadomi, John/0000-0001-6776-8661 FU Mount Zion Health Fund; American Society for Gastrointestinal Endoscopy; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080941]; VA Health Services Research and Development grant [IIR-04-427]; National Cancer Institute [1R01CA134425] FX The authors disclosed no financial relationships relevant to this publication. This work was funded in part by grants from the Mount Zion Health Fund and American Society for Gastrointestinal Endoscopy Cook Career Development Award (M.S.) and from the National Institute of Diabetes and Digestive and Kidney Diseases (K24 DK080941) (J.M.I.). Dr. Walter is supported by a VA Health Services Research and Development grant IIR-04-427 and by grant 1R01CA134425 from the National Cancer Institute. NR 67 TC 46 Z9 47 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2011 VL 74 IS 4 BP 885 EP 896 DI 10.1016/j.gie.2011.06.023 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 834ME UT WOS:000295963900021 PM 21951478 ER PT J AU Faber, JJ Anderson, DF Louey, S Thornburg, KL Giraud, GD AF Faber, J. J. Anderson, D. F. Louey, S. Thornburg, K. L. Giraud, G. D. TI Insignificant response of the fetal placental circulation to arterial hypotension in sheep SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE enalaprilat; somatic blood flow; vascular resistance; plasma renin activity; blood gases; growth ID BLOOD-FLOW; HEMODYNAMICS; ANGIOTENSIN; PRESSURE; LAMB AB Faber JJ, Anderson DF, Louey S, Thornburg KL, Giraud GD. Insignificant response of the fetal placental circulation to arterial hypotension in sheep. J Appl Physiol 111: 1042-1047, 2011. First published June 30, 2011; doi:10.1152/japplphysiol.00345.2011.-Infusion of the angiotensin-converting enzyme inhibitor enalaprilat into fetal sheep caused a profound arterial hypotension within days. Five fetal lambs were infused with enalaprilat for 8 days starting at day 128 of gestation. Total accumulated dose was 0.30 +/- 0.11 mg/kg. Arterial pressure decreased from 43.6 to 25.6 mmHg; venous pressure did not change. Biventricular output was not statistically significantly changed; placental blood flow decreased almost in proportion to the decrease in pressure but the increase in somatic flow was not statistically significant. There were no significant changes in pressure 30 min after the initial 50-mu g loading dose of enalaprilat. However, the arterial pressure responses to test doses of ANG I were largely abolished. After 1 day, however, there was a significant decrease in somatic vascular resistance, which became stronger with time, but almost no decrease in the placental resistance. We conclude that the fetal somatic circulation exhibits a slow but strong decrease in resistance but that the response to hypotension is weak or absent in the fetal placenta, possibly because it is already fully relaxed. C1 [Faber, J. J.; Anderson, D. F.; Louey, S.; Thornburg, K. L.; Giraud, G. D.] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97239 USA. [Thornburg, K. L.; Giraud, G. D.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Faber, J. J.; Anderson, D. F.; Louey, S.; Thornburg, K. L.; Giraud, G. D.] Oregon Hlth & Sci Univ, Dept Med Cardiovasc Med, Portland, OR 97239 USA. [Giraud, G. D.] Portland VA Med Ctr, Portland, OR USA. RP Giraud, GD (reprint author), Oregon Hlth & Sci Univ, Heart Res Ctr CH15H, Div Cardiovasc Med, Portland, OR 97239 USA. EM giraudg@ohsu.edu FU National Institutes of Health [P01-HD-34430]; Department of Veterans Affairs; M. Lowell Edwards Endowment FX This research was funded by a National Institutes of Health Program Project Grant (P01-HD-34430), the Department of Veterans Affairs, and the M. Lowell Edwards Endowment. NR 18 TC 2 Z9 2 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD OCT PY 2011 VL 111 IS 4 BP 1042 EP 1047 DI 10.1152/japplphysiol.00345.2011 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 834OR UT WOS:000295972000013 PM 21719727 ER PT J AU Frutos-Vivar, F Esteban, A Apezteguia, C Gonzalez, M Arabi, Y Restrepo, MI Gordo, F Santos, C Alhashemi, JA Perez, F Penuelas, O Anzueto, A AF Frutos-Vivar, Fernando Esteban, Andres Apezteguia, Carlos Gonzalez, Marco Arabi, Yaseen Restrepo, Marcos I. Gordo, Federico Santos, Cristina Alhashemi, Jamal A. Perez, Fernando Penuelas, Oscar Anzueto, Antonio TI Outcome of reintubated patients after scheduled extubation SO JOURNAL OF CRITICAL CARE LA English DT Article DE Weaning; Extubation; Outcome; Epidemiology; Noninvasive positive pressure ventilation ID INTENSIVE-CARE-UNIT; POSITIVE-PRESSURE VENTILATION; MECHANICAL VENTILATION; NONINVASIVE VENTILATION; RESPIRATORY-FAILURE; ENDOTRACHEAL INTUBATION; TRACHEAL INTUBATIONS; NOSOCOMIAL PNEUMONIA; MULTIPLE-CENTER; RISK AB Purpose: The main objective of study was to evaluate the outcome of patients who require reintubation after elective extubation. Materials and Methods: This is an observational, prospective cohort study including mechanically ventilated patients who passed successfully a spontaneous breathing trial. Patients were observed for 48 hours after extubation. During this time, reintubation or use of noninvasive positive pressure ventilation was considered as a failure. Reintubated patients were followed after the reintubation to register complications and outcome. Results: A total of 1,152 extubated patients were included in the analysis. Three hundred thirty-six patients (29%) met the criteria for extubation failure. Extubation failure was independently associated with mortality (odds ratio, 3.29; 95% confidence interval, 2.19-4.93). One hundred eighty patients (16% of overall cohort) required reintubation within 48 hours after extubation. Median time from extubation to reintubation was 13 hours (interquartile range, 6-24 hours). Reintubation was independently associated with mortality (odds ratio, 5.18; 95% confidence interval, 3.38-7.94; P < .001). Higher mortality of reintubated patients was due to the development of complications after the reintubation. Conclusions: In a large cohort of scheduled extubated patients, one third of patients developed extubation failure, of whom half needed reintubation. Reintubation was associated with increased mortality due to the development of new complications after reintubation. (C) 2011 Elsevier Inc. All rights reserved. C1 [Esteban, Andres] Hosp Univ Getafe, Intens Care Unit, Madrid 28905, Spain. [Frutos-Vivar, Fernando; Esteban, Andres; Penuelas, Oscar] CIBER Enfermedades Respiratorias, Madrid, Spain. [Apezteguia, Carlos] Hosp Profesor A Posadas, Buenos Aires, DF, Argentina. [Gonzalez, Marco] Clin Medellin, Medellin, Colombia. [Gonzalez, Marco] Univ Pontificia Bolivariana, Medellin, Colombia. [Arabi, Yaseen] King Saud Bin Abdulaziz Univ Hlth Sci, Riyadh, Saudi Arabia. [Restrepo, Marcos I.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Restrepo, Marcos I.; Anzueto, Antonio] S Texas Vet Hlth Care Syst Audie L Murphy Div, San Antonio, TX USA. [Gordo, Federico] Hosp Henares, Madrid, Spain. [Santos, Cristina] Hosp Clin Montevideo, Montevideo, Uruguay. [Alhashemi, Jamal A.] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Perez, Fernando] Hosp Clin Caracas, Caracas, Venezuela. RP Esteban, A (reprint author), Hosp Univ Getafe, Intens Care Unit, Madrid 28905, Spain. EM aesteban@ucigetafe.com RI Restrepo, Marcos/H-4442-2014 OI Frutos-Vivar, Fernando/0000-0002-4648-9636 FU CIBER Enfermedades Respiratorias from Instituto Carlos III, Spain FX This work was supported by the CIBER Enfermedades Respiratorias from Instituto Carlos III, Spain. NR 28 TC 43 Z9 44 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 J9 J CRIT CARE JI J. Crit. Care PD OCT PY 2011 VL 26 IS 5 BP 502 EP 509 DI 10.1016/j.jcrc.2010.12.015 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 834NP UT WOS:000295968800013 PM 21376523 ER PT J AU Tamuz, M Giardina, TD Thomas, EJ Menon, S Singh, H AF Tamuz, Michal Giardina, Traber Davis Thomas, Eric J. Menon, Shailaja Singh, Hardeep TI Rethinking Resident Supervision to Improve Safety: From Hierarchical to Interprofessional Models SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID SERIOUS MEDICAL ERRORS; INTENSIVE-CARE; ADVERSE EVENTS; PATIENT SAFETY; PHARMACISTS; PREVENTION; TRAINEES; TEAMWORK; IMPACT; UNITS AB BACKGROUND: Inadequate supervision is a significant contributing factor to medical errors involving trainees, but supervision in high-risk settings such as the intensive care unit (ICU) is not well studied. OBJECTIVE: We explored how residents in the ICU experienced supervision related to medication safety, not only from supervising physicians but also from other professionals. DESIGN, SETTING, MEASUREMENTS: Using qualitative methods, we examined in-depth interviews with 17 residents working in ICUs of three tertiary-care hospitals. We analyzed residents' perspectives on receiving and initiating supervision from physicians within the traditional medical hierarchy, and from other professionals, including nurses, staff pharmacists, and clinical pharmacists ("interprofessional supervision"). RESULTS: While initiating their own supervision within the traditional hierarchy, residents believed in seeking assistance from fellows and attendings, and articulated rules of thumb for doing so; however, they also experienced difficulties. Some residents were concerned that their questions would reflect poorly on them; others were embarrassed by their mistaken decisions. Conversely, residents described receiving interprofessional supervision from nurses and pharmacists, who proactively monitored, intervened in, and guided residents' decisions. Residents relied on nurses and pharmacists for nonjudgmental answers to their queries, especially after-hours. To enhance both types of supervision, residents emphasized the importance of improving interpersonal communication skills. CONCLUSIONS: Residents depended on interprofessional supervision when making decisions regarding medications in the ICU. Improving interprofessional supervision, which thus far has been underrecognized and underemphasized in graduate medical education, can potentially improve medication safety in high-risk settings. Journal of Hospital Medicine 2011;6:445-452. (C) 2011 Society of Hospital Medicine C1 [Tamuz, Michal] Suny Downstate Med Ctr, Sch Publ Hlth, Dept Hlth Policy & Management, Brooklyn, NY 11203 USA. [Giardina, Traber Davis; Menon, Shailaja; Singh, Hardeep] Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Giardina, Traber Davis; Menon, Shailaja; Singh, Hardeep] Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA. [Thomas, Eric J.] Univ Texas Houston, Mem Hermann Ctr Healthcare Qual & Safety, Med Sch Houston, Div Gen Med,Dept Med, Houston, TX USA. RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu OI Davis Giardina, Traber/0000-0002-9184-6524 FU AHRQ [1PO1HS1154401]; Houston VA HSR&D Center of Excellence [HFP90-020] FX Project supported by AHRQ grant #1PO1HS1154401, and in part by the Houston VA HSR&D Center of Excellence (HFP90-020). NR 40 TC 6 Z9 6 U1 1 U2 15 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 OCT PY 2011 VL 6 IS 8 BP 445 EP 452 DI 10.1002/jhm.919 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 836DX UT WOS:000296090700004 PM 21990173 ER PT J AU Wei, JN Kneeland, PP Dhaliwal, G AF Wei, Jennie Kneeland, Patrick P. Dhaliwal, Gurpreet TI Cracking the Case SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID LEVAMISOLE; AGRANULOCYTOSIS C1 [Wei, Jennie; Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Kneeland, Patrick P.] Providence Reg Med Ctr, Div Hosp Med, Everett, WA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. RP Wei, JN (reprint author), Univ Calif San Francisco, Dept Med, 505 Parnassus Ave,Room M987, San Francisco, CA 94143 USA. EM jennie.wei@ucsf.edu NR 16 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 2011 VL 6 IS 8 BP 480 EP 483 DI 10.1002/jhm.902 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 836DX UT WOS:000296090700009 PM 21990177 ER PT J AU Guan, D Higgs, MH Horton, LR Spain, WJ Foehring, RC AF Guan, D. Higgs, M. H. Horton, L. R. Spain, W. J. Foehring, R. C. TI Contributions of Kv7-mediated potassium current to sub- and suprathreshold responses of rat layer II/III neocortical pyramidal neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE linopirdine; M current; motor cortex; somatosensory cortex; XE-991 ID NEUROTRANSMITTER-RELEASE ENHANCER; SPIKE FREQUENCY ADAPTATION; PERSISTENT NA+ CURRENT; AREA DOPAMINE NEURONS; LINOPIRDINE DUP 996; HIPPOCAMPAL-NEURONS; K+ CURRENT; SYMPATHETIC NEURONS; CORTICAL-NEURONS; MAMMALIAN-CELLS AB Guan D, Higgs MH, Horton LR, Spain WJ, Foehring RC. Contributions of Kv7-mediated potassium current to sub-and suprathreshold responses of rat layer II/III neocortical pyramidal neurons. J Neurophysiol 106: 1722-1733, 2011. First published June 22, 2011; doi: 10.1152/jn.00211.2011.-After block of Kv1- and Kv2-mediated K+ currents in acutely dissociated neocortical pyramidal neurons from layers II/III of rat somatosensory and motor cortex, the remaining current is slowly activating and persistent. We used whole cell voltage clamp to show that the Kv7 blockers linopirdine and XE-991 blocked a current with similar kinetics to the current remaining after combined block of Kv1- and Kv2 channels. This current was sensitive to low doses of linopirdine and activated more slowly and at more negative potentials than Kv1- or Kv2-mediated current. The Kv7-mediated current decreased in amplitude with time in whole cell recordings, but in most cells the current was stable for several minutes. Current in response to a traditional M-current protocol was blocked by muscarine, linopirdine, and XE-991. Whole cell slice recordings revealed that the Q 10 for channel deactivation was similar to 2.5. Sharp electrode current-clamp recordings from adult pyramidal cells demonstrated that block of Kv7-mediated current with XE-991 reduced rheobase, shortened the latency to firing to near rheobase current, induced more regular firing at low current intensity, and increased the rate of firing to a given current injection. XE-991 did not affect single action potentials or spike frequency adaptation. Application of XE-991 also eliminated subthreshold voltage oscillations and increased gain for low-frequency inputs (<10 Hz) without affecting gain for higher frequency inputs. These data suggest important roles for Kv7 channels in subthreshold regulation of excitability, generation of theta-frequency subthreshold oscillations, regulation of interspike intervals, and biasing selectivity toward higher frequency inputs. C1 [Guan, D.; Horton, L. R.; Foehring, R. C.] Univ Tennessee, Dept Anat & Neurobiol, Memphis, TN 38163 USA. [Higgs, M. H.; Spain, W. J.] Vet Affairs Puget Sound Hlth Care Syst, Neurol, Seattle, WA USA. RP Foehring, RC (reprint author), Univ Tennessee, Dept Anat & Neurobiol, 855 Monroe Ave, Memphis, TN 38163 USA. EM rfoehrin@uthsc.edu FU National Institute of Neurological Disorders and Stroke [NS044163]; Veterans Affairs Merit Award; Veterans Affairs Epilepsy Center of Excellence FX This work was funded by National Institute of Neurological Disorders and Stroke Grant NS044163 (to R. C. Foehring) and a Veterans Affairs Merit Award and Veterans Affairs Epilepsy Center of Excellence ( to W. J. Spain). NR 86 TC 16 Z9 16 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 2011 VL 106 IS 4 BP 1722 EP 1733 DI 10.1152/jn.00211.2011 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 836EJ UT WOS:000296092000014 PM 21697446 ER PT J AU Grunwald, L Newcomb, CW Daniel, E Kacmaz, RO Jabs, DA Levy-Clarke, GA Nussenblatt, RB Rosenbaum, JT Suhler, EB Thorne, JE Foster, CS Kempen, JH AF Grunwald, Lili Newcomb, Craig W. Daniel, Ebenezer Kacmaz, R. Oktay Jabs, Douglas A. Levy-Clarke, Grace A. Nussenblatt, Robert B. Rosenbaum, James T. Suhler, Eric B. Thorne, Jennifer E. Foster, C. Stephen Kempen, John H. CA Syst Immunosuppressive Therapy Eye TI Risk of Relapse in Primary Acute Anterior Uveitis SO OPHTHALMOLOGY LA English DT Article ID OCULAR INFLAMMATION; CLINICAL-FEATURES; HLA-B27 UVEITIS; DISEASES; OUTCOMES AB Purpose: To evaluate the risk of and risk factors for a second episode (relapse) among patients with remitted primary anterior uveitis. Design: Retrospective cohort study. Participants: Patients with primary anterior uveitis presenting to 1 of 4 academic ocular inflammation subspecialty practices achieving remission of the primary episode within 90 days of initial uveitis diagnosis. Methods: Data were obtained by standardized chart review. Main Outcome Measures: Time to relapse of anterior uveitis and risk factors for relapse. Results: We included 102 patients with a first episode of anterior uveitis who were seen within 90 days of first-ever uveitis onset and followed for 165 person-years after achieving remission of the initial episode. Most patients were female (60%) and white (78%). Forty patients had a recurrence of anterior uveitis. The incidence of relapse was 24% per person-year (95% confidence interval [CI], 17%-33%). At 1.5 years after remission, 61% (95% CI, 48%-71%) were still in remission. Younger adults had significantly higher relapse risk than middle-aged adults (hazard ratio [18-to 35-year-old persons vs. 35-to 55-year-old persons], 2.7; 95% CI, 1.3-6.0). Conclusions: Our results suggest that many patients with remitted primary anterior uveitis presenting for tertiary uveitis care will relapse. Age in the young adult range was associated with higher risk of relapse. Given the high relapse risk, management of patients with primary anterior uveitis should include an explicit plan for detecting and managing relapses. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2011;118: 1911-1915 (C) 2011 by the American Academy of Ophthalmology. C1 [Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA. [Newcomb, Craig W.; Kempen, John H.] Univ Penn, Univ Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Newcomb, Craig W.; Kempen, John H.] Univ Penn, Dept Biostat & Epidemiol & Ophthalmol, Philadelphia, PA 19104 USA. [Kacmaz, R. Oktay; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Kacmaz, R. Oktay; Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.; Thorne, Jennifer E.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. [Jabs, Douglas A.; Thorne, Jennifer E.] Johns Hopkins Univ, Dept & Epidemiol, Baltimore, MD USA. [Levy-Clarke, Grace A.] St Lukes Cataract & Laser Inst, Tarpon Springs, FL USA. [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM john.kempen@uphs.upenn.edu OI Daniel, Ebenezer/0000-0002-2027-2316 FU National Eye Institute [EY014943]; National Eye Institute; Department of Veterans' Affairs FX Supported primarily by National Eye Institute Grant EY014943 (Dr. Kempen). Additional support was provided by Research to Prevent Blindness and the Paul and Evanina Mackall Foundation. During part of the conduct of this project, Dr Kempen was an RPB James S. Adams Special Scholar Award recipient, Dr. Thorne was an RPB Harrington Special Scholar Award recipient, and Drs. Jabs and Rosenbaum were Research to Prevent Blindness Senior Scientific Investigator Award recipients. Dr. Levy-Clarke was previously supported by and Dr. Nussenblatt continues to be supported by intramural funds of the National Eye Institute. Dr. Suhler receives support from the Department of Veterans' Affairs. NR 23 TC 6 Z9 6 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 2011 VL 118 IS 10 BP 1911 EP 1915 DI 10.1016/j.ophtha.2011.02.044 PG 5 WC Ophthalmology SC Ophthalmology GA 835WG UT WOS:000296066900004 PM 21680024 ER PT J AU Bauman, WA Biering-Sorensen, F Krassioukov, A AF Bauman, W. A. Biering-Sorensen, F. Krassioukov, A. TI The International Spinal Cord Injury Endocrine and Metabolic Function Basic Data Set SO SPINAL CORD LA English DT Article DE spinal cord injury; international data set; endocrine; metabolic; diabetes; osteoporosis ID BONE; TESTOSTERONE; MORTALITY; DIAGNOSIS; MEN AB Objective: To develop the International Spinal Cord Injury (SCI) Endocrine and Metabolic Function Basic Data Set within the framework of the International SCI Data Sets that would facilitate consistent collection and reporting of basic endocrine and metabolic findings in the SCI population. Setting: International. Methods: The International SCI Endocrine and Metabolic Function Data Set was developed by a working group. The initial data set document was revised on the basis of suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations and societies, and individual reviewers. In addition, the data set was posted for 2 months on ISCoS and ASIA websites for comments. Results: The final International SCI Endocrine and Metabolic Function Data Set contains questions on the endocrine and metabolic conditions diagnosed before and after spinal cord lesion. If available, information collected before injury is to be obtained only once, whereas information after injury may be collected at any time. These data include information on diabetes mellitus, lipid disorders, osteoporosis, thyroid disease, adrenal disease, gonadal disease and pituitary disease. The question of gonadal status includes stage of sexual development and that for females also includes menopausal status. Data will be collected for body mass index and for the fasting serum lipid profile. The complete instructions for data collection and the data sheet itself are freely available on the websites of ISCoS (http://www.iscos.org.uk) and ASIA (http://www.asia-spinalinjury.org). Spinal Cord (2011) 49, 1068-1072; doi:10.1038/sc.2011.51; published online 17 May 2011 C1 [Bauman, W. A.] James J Peters Vet Affairs Med Ctr, Vet Affairs Rehabil Res & Dev Ctr Excellence Med, Bronx, NY 10468 USA. [Bauman, W. A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauman, W. A.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Biering-Sorensen, F.] Univ Copenhagen, Rigshosp, Clin Spinal Cord Injuries, Ctr Neurosci, DK-2100 Copenhagen, Denmark. [Biering-Sorensen, F.] Univ Copenhagen, Fac Hlth Sci, DK-2100 Copenhagen, Denmark. [Krassioukov, A.] Univ British Columbia, ICORD, Dept Med, Vancouver, BC V5Z 1M9, Canada. [Krassioukov, A.] Vancouver Coastal Hlth, Vancouver, BC, Canada. RP Bauman, WA (reprint author), James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. EM william.bauman@va.gov FU Department of Veterans Affairs Rehabilitation Research and Development Service [B4162C] FX We are thankful for the comments and suggestions received from Susan Charlifue, Lawrence Vogel, Vanessa Noonan, Marcalee Sipski Alexander, Inge Eriks-Hoogland, and Michael DeVivo. We wish to thank the Department of Veterans Affairs Rehabilitation Research and Development Service for their support (grant B4162C). NR 26 TC 5 Z9 5 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD OCT PY 2011 VL 49 IS 10 BP 1068 EP 1072 DI 10.1038/sc.2011.51 PG 5 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 833YY UT WOS:000295923200009 PM 21577217 ER PT J AU Mrnak-Meyer, J Tate, SR Tripp, JC Worley, MJ Jajodia, A McQuaid, JR AF Mrnak-Meyer, Jennifer Tate, Susan R. Tripp, Jessica C. Worley, Matthew J. Jajodia, Archana McQuaid, John R. TI Predictors of Suicide-Related Hospitalization among U.S. Veterans Receiving Treatment for Comorbid Depression and Substance Dependence Who is the Riskiest of the Risky? SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID PERSIAN-GULF-WAR; US VETERANS; MOOD REGULATION; DISORDERS; MORTALITY; ABUSERS AB This study examined whether widely accepted suicide risk factors are useful in predicting suicide-related hospitalization, beyond history of a suicide attempt, in high-risk treatment-seeking veterans with depression and substance dependence. Negative mood regulation expectancies were the only significant predictor of hospitalization during 6-months of outpatient treatment. History of a suicide attempt was the only significant predictor of hospitalization during the one-year follow-up period. Results suggest that within high-risk populations, standard suicide risk factors may not identify individuals who will engage in suicidal behaviors resulting in hospitalization. Assessing negative mood regulation expectations may assist in identifying those most at risk. C1 [Mrnak-Meyer, Jennifer; Tate, Susan R.; Tripp, Jessica C.; Jajodia, Archana] VA San Diego Healthcare Syst, San Diego, CA 92161 USA. [Worley, Matthew J.] Univ Calif San Diego, San Diego State Univ, Joint Doctoral Program Clin Psychol, San Diego, CA 92103 USA. [McQuaid, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [McQuaid, John R.] Univ Calif San Francisco, San Francisco, CA 94143 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 FU NIAAA NIH HHS [T32 AA013525]; NIDA NIH HHS [F31 DA030861] NR 38 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0363-0234 J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD OCT PY 2011 VL 41 IS 5 BP 532 EP 542 DI 10.1111/j.1943-278X.2011.00051.x PG 11 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 834DG UT WOS:000295938900006 PM 21815915 ER PT J AU Chen, G Carlson, VCC Wang, J Beck, A Heinz, A Ron, D Lovinger, DM Buck, KJ AF Chen, Gang Carlson, Verginia C. Cuzon Wang, Jun Beck, Anne Heinz, Andreas Ron, Dorit Lovinger, David M. Buck, Kari J. TI Striatal Involvement in Human Alcoholism and Alcohol Consumption, and Withdrawal in Animal Models SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE c-Fos; Electrophysiology; fMRI; Fyn Kinase; PET; Self-Administration ID NR2B-CONTAINING NMDA RECEPTORS; ETHANOL WITHDRAWAL; PREFRONTAL CORTEX; DORSAL STRIATUM; STRIATOPALLIDAL NEURONS; MACACA-FASCICULARIS; CHROMOSOME-4 LOCUS; VENTRAL STRIATUM; BASAL GANGLIA; C57BL/6J MICE AB Background: Different regions of the striatum may have distinct roles in acute intoxication, alcohol seeking, dependence, and withdrawal. Methods: The recent advances are reviewed and discussed in our understanding of the role of the dorsolateral striatum (DLS), dorsomedial striatum (DMS), and ventral striatum in behavioral responses to alcohol, including alcohol craving in abstinent alcoholics, and alcohol consumption and withdrawal in rat, mouse, and nonhuman primate models. Results: Reduced neuronal activity as well as dysfunctional connectivity between the ventral striatum and the dorsolateral prefrontal cortex is associated with alcohol craving and impairment of new learning processes in abstinent alcoholics. Within the DLS of mice and nonhuman primates withdrawn from alcohol after chronic exposure, glutamatergic transmission in striatal projection neurons is increased, while GABAergic transmission is decreased. Glutamatergic transmission in DMS projection neurons is also increased in ethanol withdrawn rats. Ex vivo or in vivo ethanol exposure and withdrawal causes a long-lasting increase in NR2B subunit-containing NMDA receptor activity in the DMS, contributing to ethanol drinking. Analyses of neuronal activation associated with alcohol withdrawal and site-directed lesions in mice implicate the rostroventral caudate putamen, a ventrolateral segment of the DMS, in genetically determined differences in risk for alcohol withdrawal involved in physical association of the multi-PDZ domain protein, MPDZ, with 5-HT(2C) receptors and/or NR2B. Conclusions: Alterations of dopaminergic, glutamatergic, and GABAergic signaling within different regions of the striatum by alcohol is critical for alcohol craving, consumption, dependence, and withdrawal in humans and animal models. C1 [Chen, Gang; Buck, Kari J.] Portland VA Med Ctr, Dept Behav Neurosci, Portland, OR USA. [Chen, Gang; Buck, Kari J.] Portland VA Med Ctr, Portland Alcohol Res Ctr, Portland, OR USA. [Chen, Gang; Buck, Kari J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Carlson, Verginia C. Cuzon; Lovinger, David M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. [Wang, Jun; Ron, Dorit] Univ Calif San Francisco, Dept Neurol, Ernest Gallo Res Ctr, San Francisco, CA USA. [Beck, Anne; Heinz, Andreas] Charite, Dept Psychiat & Psychotherapy, D-13353 Berlin, Germany. RP Chen, G (reprint author), Univ Minnesota, Inst Translat Neurosci, RM 4-140,MBB 2101 6th SE,East Campus, Minneapolis, MN 55455 USA. EM hdn_2001@yahoo.com RI Wang, Jun/N-8472-2015; Wang, Jun/M-2337-2016 OI Wang, Jun/0000-0002-0085-4722; Wang, Jun/0000-0002-0085-4722 FU division of Intramural Clinical and Basic Research NIAAA [AA13510, AA13641]; State of California for medical research on alcohol and substance abuse through the University of California, San Francisco; Department of Veterans Affairs; German Research Foundation (Deutsche Forschungsgemeinschaft) [HE2597/4-3, 7-3]; Bernstein Center for Computational Neuroscience Berlin [01GQ0411, 01GS08159]; [R01AA014366]; [MH13438]; [AA011114]; [AA10760]; [DA05228] FX The work described in this review was supported by the division of Intramural Clinical and Basic Research NIAAA, AA13510, AA13641 (VCCC, DML); R01AA014366, MH13438, and funds provided by the State of California for medical research on alcohol and substance abuse through the University of California, San Francisco (DR); AA011114, AA10760, DA05228, and the Department of Veterans Affairs (KJB); the German Research Foundation (Deutsche Forschungsgemeinschaft, HE2597/4-3 and 7-3) and the Bernstein Center for Computational Neuroscience Berlin (Bundesministerium fur Bildung und Forschung Grants 01GQ0411 and 01GS08159) (AH). NR 80 TC 33 Z9 35 U1 1 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 2011 VL 35 IS 10 BP 1739 EP 1748 DI 10.1111/j.1530-0277.2011.01520.x PG 10 WC Substance Abuse SC Substance Abuse GA 824QX UT WOS:000295218200006 PM 21615425 ER PT J AU Anacker, AMJ Loftis, JM Ryabinin, AE AF Anacker, Allison M. J. Loftis, Jennifer M. Ryabinin, Andrey E. TI Alcohol Intake in Prairie Voles is Influenced by the Drinking Level of a Peer SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Prairie Voles; Social Behavior; Alcohol Self-Administration; Peer Influence; Microtus ochrogaster ID ETHANOL-CONSUMPTION; SOCIAL INFLUENCES; RATS; MICE; BEHAVIOR; SOCIALIZATION; ADOLESCENTS; EXPRESSION; FRIENDSHIP; SELECTION AB Background: Peer interactions can have important effects on alcohol-drinking levels, in some cases increasing use, and in other cases preventing it. In a previous study, we have established the prairie vole as a model animal for the effects of social relationships on alcohol intake and have observed a correlation of alcohol intake between individual voles housed together as pairs. Here, we investigated this correlated drinking behavior, hypothesizing that 1 animal alters its alcohol intake to match the drinking of its partner. Methods: Adult prairie voles were tested for baseline drinking levels with continuous access to 10% alcohol and water for 4 days. In Experiment 1, high alcohol drinkers (> 9 g/kg/d) were paired with low alcohol drinkers (< 5 g/kg/d) of the same sex on either side of a mesh divider for 4 days with continuous access to the same 2-bottle choice test. In Experiment 2, high drinkers were paired with high drinkers and low drinkers paired with low drinkers. In both experiments, animals were again separated following pairing, and drinking was retested in isolation. In Experiment 3, alcohol-naive animals were tested for saccharin consumption (0.05%) first in isolation and then in high saccharin drinkers paired with low saccharin drinkers, and then in another isolation period. Results: In Experiment 1, high drinkers paired with low drinkers significantly decreased their alcohol intake and preference from baseline drinking in isolation, and drinking levels remained significantly lower during isolation following pairing. Interestingly, there was variability between pairs in whether the high drinker decreased or the low drinker increased intake. In Experiment 2, high drinkers paired with high drinkers did not significantly change their intake level or preference, nor did low drinkers paired with low drinkers, and no changes occurred during the subsequent isolation. In Experiment 3, there was no change in saccharin intake or preference when high drinkers were paired with high drinkers or low paired with low, or in the subsequent isolation. Conclusions: Alcohol drinking of prairie voles can be altered under social conditions, such that 1 animal changes its alcohol intake to more closely match the intake of the other animal, helping to explain previous findings of correlated alcohol drinking. The effect does not extend to saccharin, a naturally rewarding sweet substance. This behavior can be used to model the peer pressure that can often affect alcohol intake in humans. C1 [Anacker, Allison M. J.; Loftis, Jennifer M.; Ryabinin, Andrey E.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Loftis, Jennifer M.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR USA. [Loftis, Jennifer M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Ryabinin, AE (reprint author), 3181 SW Sam Jackson Pk Rd,Mail Code L470, Portland, OR 97239 USA. EM ryabinin@ohsu.edu FU NIH [AA016886, AA02013601, AA007468]; ARCS Foundation Portland Chapter; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and Clinical Sciences Research and Development FX This work was supported by NIH grants AA016886 to AER, AA02013601 to AMJA, institutional training grant AA007468.23, and the ARCS Foundation Portland Chapter M&M award to AMJA. The authors also thank the PVAMC VMU staff for their contributions to the colony management and animal care. This material is the result of work supported with resources and the use of facilities at the Portland Veterans Affairs Medical Center. JML is supported by a career development award from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and Clinical Sciences Research and Development. NR 33 TC 25 Z9 25 U1 1 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 2011 VL 35 IS 10 BP 1884 EP 1890 DI 10.1111/j.1530-0277.2011.01533.x PG 7 WC Substance Abuse SC Substance Abuse GA 824QX UT WOS:000295218200020 PM 21575019 ER PT J AU Keenan, RT Pillinger, MH AF Keenan, Robert T. Pillinger, Michael H. TI Steroid for Gout: Myth or Elixir? Reply SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter ID COLCHICINE; GUIDELINES; TOXICITY C1 [Keenan, Robert T.] Duke Univ, Sch Med, Div Rheumatol & Immunol, Durham, NC 27708 USA. [Pillinger, Michael H.] NYU, New York Harbor Hlth Care Syst, US Dept Vet Affairs, Sect Rheumatol,Div Rheumatol,Sch Med, New York, NY USA. RP Keenan, RT (reprint author), Duke Univ, Sch Med, Div Rheumatol & Immunol, Durham, NC 27708 USA. NR 8 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 2011 VL 124 IS 10 BP E19 EP E19 DI 10.1016/j.amjmed.2011.04.029 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 831EZ UT WOS:000295712800014 ER PT J AU Gamble, RG Dellavalle, RP AF Gamble, Ryan G. Dellavalle, Robert P. TI Ion-Exchange Water Softener Use and Eczema SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material ID ATOPIC-DERMATITIS SEVERITY; 6 AREA; HARDNESS; PREVALENCE; SCORE C1 [Dellavalle, Robert P.] Denver VA Med Ctr, Dept Veteran Affairs, Denver, CO 80220 USA. [Gamble, Ryan G.] Univ Colorado Denver, Dept Dermatol, Sch Med, Aurora, CO USA. RP Dellavalle, RP (reprint author), Denver VA Med Ctr, Dept Veteran Affairs, 1055 Clermont St,POB 165, Denver, CO 80220 USA. EM robert.dellavalle@ucdenver.edu RI Dellavalle, Robert/L-2020-2013 OI Dellavalle, Robert/0000-0001-8132-088X NR 10 TC 1 Z9 1 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD OCT PY 2011 VL 147 IS 10 BP 1208 EP 1210 PG 3 WC Dermatology SC Dermatology GA 834FH UT WOS:000295944300015 PM 22006138 ER PT J AU Kent, RD Robbins, J AF Kent, Ray D. Robbins, JoAnne TI INTRODUCTION TO THE SPECIAL ISSUE, INTEGRATIVE NEURAL SYSTEMS UNDERLYING VITAL AERODIGESTIVE TRACT FUNCTIONS SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article ID MUSCLES; SPEECH; DYNAMICS; NETWORK; TONGUE AB This special issue is an outgrowth of the conference, "Integrative Neural Systems Underlying Vital Aerodigestive Tract Functions,'' held in Madison, Wisconsin, June 17-19, 2010. The program included 3 plenary lectures, 4 keynote lectures, and 15 scientific papers. In addition, workgroup presentations, and panel discussions provided opportunities for general discussion and integration of information in a multidisciplinary context. This special issue is intended to disseminate major conclusions, potential directions for research, and unique approaches for consideration of application to clinical practice arising from the conference. The contributions assembled in this issue include 7 articles based on the plenary or keynote lectures, an invited perspective on laryngeal function, and a summary of workgroup discussions held at the conference. In this introductory article, names printed in upper case refer to articles in this special issue. C1 [Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Kent, Ray D.] Univ Wisconsin, Waisman Ctr, Dept Communicat Disorders, Madison, WI 53705 USA. [Robbins, JoAnne] Univ Wisconsin, Dept Med, Madison, WI USA. RP Robbins, J (reprint author), William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. EM jrobbin2@wisc.edu FU NIDCD NIH HHS [#1R13DC009556-01A109] NR 22 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD OCT PY 2011 VL 33 SU 1 SI SI BP S1 EP S4 DI 10.1002/hed.21900 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 833KS UT WOS:000295884700001 PM 21901778 ER PT J AU Malandraki, GA Johnson, S Robbins, J AF Malandraki, Georgia A. Johnson, Sterling Robbins, JoAnne TI FUNCTIONAL MRI OF SWALLOWING: FROM NEUROPHYSIOLOGY TO NEUROPLASTICITY SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE fMRI; swallowing; neuroimaging; neuroplasticity; dysphagia ID CEREBRAL CORTICAL REPRESENTATION; PENETRATION-ASPIRATION SCALE; MAGNETIC-RESONANCE; BRAIN-FUNCTION; SENSORY STIMULATION; NEURAL PLASTICITY; OLDER-ADULTS; ACTIVATION; DYSPHAGIA; FMRI AB Swallowing is a complex neurogenic sensorimotor process involving all levels of the neuraxis and a vast number of muscles and anatomic structures. Disruption of any of these anatomic or functional components can lead to swallowing disorders (also known as dysphagia). Understanding the neural pathways that govern swallowing is necessary in diagnosing and treating patients with dysphagia. Functional MRI (fMRI) is a prevalent and effective neuroimaging method that has been used to study the complex neurophysiologic control of swallowing in vivo. This article presents a summary of the research studies that have used fMRI to study the neural control of swallowing in normal subjects and dysphagic patients, and to investigate the effects of swallowing treatments on neuroplasticity. Methodologic challenges and caveats are discussed, and a case study of a pre-posttreatment paradigm is presented to highlight potential future directions of fMRI applications in swallowing research and clinical practice. (C) 2011 Wiley Periodicals, Inc. Head Neck 33: S14-S20, 2011 C1 [Malandraki, Georgia A.] Columbia Univ, Teachers Coll, Program Speech & Language Pathol, Dept Biobehav Sci, New York, NY 10027 USA. [Malandraki, Georgia A.; Johnson, Sterling; Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Malandraki, Georgia A.; Johnson, Sterling; Robbins, JoAnne] Univ Wisconsin, Dept Med, Madison, WI USA. RP Malandraki, GA (reprint author), Columbia Univ, Teachers Coll, Program Speech & Language Pathol, Dept Biobehav Sci, New York, NY 10027 USA. EM malandraki@tc.columbia.edu OI Johnson, Sterling/0000-0002-8501-545X FU NIA NIH HHS [P50 AG033514]; NICHD NIH HHS [P30 HD003352]; NIDCD NIH HHS [#1R13DC009556-01A1S1, R13 DC009556] NR 62 TC 6 Z9 9 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD OCT PY 2011 VL 33 SU 1 SI SI BP S14 EP S20 DI 10.1002/hed.21903 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 833KS UT WOS:000295884700004 PM 21901779 ER PT J AU Robbins, J AF Robbins, JoAnne TI UPPER AERODIGESTIVE TRACT NEUROFUNCTIONAL MECHANISMS: LIFELONG EVOLUTION AND EXERCISE SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE dysphagia; dysarthria; obstructive sleep apnea; sarcopenia; exercise; neural maturation; neuromuscular plasticity ID LINGUAL EXERCISE; ORAL-PHARYNGEAL; DYSPHAGIA; STRENGTH; AGE; PLASTICITY; SARCOPENIA; PRESSURE; MUSCLE; ADULTS AB The transformation of the upper aerodigestive tract - oral cavity, pharynx, and larynx - serves the functions of eating, speaking, and breathing during sleeping and waking hours. These life-sustaining functions may be produced by a central neural sensorimotor system that shares certain neuroanatomic networks while maintaining separate neural functional systems and network structures. Current understanding of development, maturation, underlying neural correlates, and integrative factors are discussed in light of currently available imaging modalities and recently emerging interventions. Exercise and an array of additional treatments together seem to provide promising translational pathways for evidence-based innovation, novel habilitation, and rehabilitation strategies and delay, or even prevent neuromuscular decline cross-cutting functions and supporting quality of life throughout increasingly enduring lifespans. (C) 2011 Wiley Periodicals, Inc. Head Neck 33: S30-S36, 2011 C1 [Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Robbins, JoAnne] Univ Wisconsin, Dept Med, Madison, WI USA. RP Robbins, J (reprint author), William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. EM jrobbin2@wisc.edu FU NIDCD NIH HHS [#1R13DC009556-01A1S1, R13 DC009556] NR 51 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD OCT PY 2011 VL 33 SU 1 SI SI BP S30 EP S36 DI 10.1002/hed.21902 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 833KS UT WOS:000295884700007 PM 21910155 ER PT J AU Federman, AD Keyhani, S AF Federman, Alex D. Keyhani, Salomeh TI Physicians' participation in the Physicians' Quality Reporting Initiative and their perceptions of its impact on quality of care SO HEALTH POLICY LA English DT Article DE Quality improvement; Reporting; Physician incentives; Health care reform ID PAY-FOR-PERFORMANCE; HEALTH-CARE; PROGRAMS; IMPROVEMENT; PROSPECTS; MEDICARE; VIEWS; COST AB Background: Medicare established the Physicians Quality Reporting Initiative (PQRI, recently renamed the Physicians Quality Reporting System) to increase reporting of quality metrics and promote healthcare quality. Objective: To identify characteristics of PQRI participants and examine their beliefs about its impact. Design: National survey of 4934 U.S. physicians, conducted June through October 2009. Setting: All practice settings. Participants: Randomly selected physicians categorized as primary care, medical specialists, surgeons, other specialists. Measurements: Beliefs about impact of PQRI reporting on quality. Results: The response rate was 49.8%. There were no significant differences between respondents and non-respondents by age, gender, specialty, and region. Thirty-eight percent participated in the PQRI, and were more likely than non-participants to be practice owners (69.0% vs. 57.1%, p < .0001) and to receive performance bonuses through their employer or practice (50.4% vs. 37.0%, p < .0001). Half of PQRI participants believed it had no impact on quality. Medical specialists (57.0%) and surgeons (55.1%) were more likely than primary care (40.4%) and other physicians (45.7%) to say that PQRI has no impact on quality (p = .004). Conclusions: Most PQRI participants believed it had little if any impact on quality. Medicare should identify the reasons behind physicians' negative views while it works to expand the Physicians Quality Reporting System. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Federman, Alex D.; Keyhani, Salomeh] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY 10029 USA. [Keyhani, Salomeh] James J Peters Vet Adm Med Ctr, Bronx, NY USA. [Keyhani, Salomeh] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA. [Keyhani, Salomeh] Univ Calif San Francisco, Div Gen Internal Med, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Federman, AD (reprint author), Mt Sinai Sch Med, Div Gen Internal Med, Box 1087,1 Gustave L Levy Pl, New York, NY 10029 USA. EM alex.federman@mssm.edu FU Robert Wood Johnson Foundation; National Institute on Aging; American Federation on Aging Research; Veterans Administration Health Services Research and Development Service FX This study was supported by a grant from the Robert Wood Johnson Foundation. Additionally, Dr. Federman is supported in part by a Paul B. Beeson career development award in aging related research from the National Institute on Aging and the American Federation on Aging Research, and Dr. Keyhani is supported by a career development award from the Veterans Administration Health Services Research and Development Service. NR 28 TC 16 Z9 16 U1 2 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8510 J9 HEALTH POLICY JI Health Policy PD OCT PY 2011 VL 102 IS 2-3 BP 229 EP 234 DI 10.1016/j.healthpol.2011.05.003 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 831BR UT WOS:000295704200014 PM 21628079 ER PT J AU Kanwal, F Kramer, JR Buchanan, P Asch, S Assioun, Y Gary, J Li, J Bacon, BR El-Serag, H AF Kanwal, Fasiha Kramer, Jennifer R. Buchanan, Paula Asch, Steven Assioun, Youssef Gary, Julie Li, Juan Bacon, Bruce R. El-Serag, Hashem TI THE QUALITY OF CARE PROVIDED TO PATIENTS WITH CIRRHOSIS AND ASCITES SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kanwal, Fasiha; Gary, Julie; Li, Juan] St Louis VA Med Ctr, St Louis, MO USA. [Kanwal, Fasiha; Buchanan, Paula; Assioun, Youssef; Gary, Julie; Bacon, Bruce R.] St Louis Univ, Sch Med, St Louis, MO USA. [Kramer, Jennifer R.; El-Serag, Hashem] Houston VA, Houston, TX USA. [Kramer, Jennifer R.; El-Serag, Hashem] Baylor Coll Med, Houston, TX 77030 USA. [Asch, Steven] Greater Los Angeles VA Healthcare Syst, Los Angeles, 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 408A EP 408A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002098 ER PT J AU Rongey, C Hamilton, N Asch, S Knight, S AF Rongey, Catherine Hamilton, Nathan Asch, Steven Knight, Sara TI GEOGRAPHIC DIFFERENCES IN ACCESS TO AND QUALITY OF LIVER CARE AMONG A NATIONAL COHORT OF VETERAN HEALTH ADMINISTRATION PATIENTS WITH HEPATITIS C SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Rongey, Catherine; Hamilton, Nathan; Knight, Sara] San Francisco VA Med Ctr, San Francisco, CA USA. [Rongey, Catherine; Knight, Sara] UCSF, San Francisco, CA USA. [Asch, Steven] Univ Calif Los Angeles, Los Angeles, CA USA. [Asch, Steven] WLA VAMC, Los Angeles, 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 410A EP 410A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002102 ER PT J AU Zhu, NL Liu, JC Machida, K Tsukamoto, H AF Zhu, Nian-Ling Liu, Jian-Chang Machida, Keigo Tsukamoto, Hidekazu TI DLK1 AS AN ANTI-ADIPOGENIC MEDIATOR FOR ACTIVATION OF HEPATIC STELLATE CELLS IN LIVER FIBROSIS, REGENERATION, AND CANCER SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Zhu, Nian-Ling; Liu, Jian-Chang; Machida, Keigo; Tsukamoto, Hidekazu] Univ So Calif, So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA USA. [Zhu, Nian-Ling] Univ So Calif, Dept Pathol, Los Angeles, CA 90089 USA. [Liu, Jian-Chang; Machida, Keigo] Univ So Calif, Dept Mol Microbiol & Immunol, Los Angeles, CA USA. [Tsukamoto, Hidekazu] Greater Los Angeles VA Healthcare Syst, Los Angeles, 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 424A EP 424A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002132 ER PT J AU Chan, K Lai, MN Groessl, EJ Hanchate, AD Hernandez, L Wong, JB Clark, J Asch, S Gifford, AL Ho, SB AF Chan, Kee Lai, Mai-Ngan Groessl, Erik J. Hanchate, Amresh D. Hernandez, Leilani Wong, John B. Clark, Jack Asch, Steven Gifford, Allen L. Ho, Samuel B. TI LONG TERM CLINICAL IMPACT OF DIRECT ANTIVIRAL AGENT (DAA) THERAPY FOR UNTREATED CHRONIC HEPATITIS C GENOTYPE 1 INFECTION IN THE VETERANS HEALTH ADMINISTRATION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Lai, Mai-Ngan; Groessl, Erik J.; Ho, Samuel B.] VA San Diego Healthcare Syst, Gastroenterol, San Diego, CA USA. [Chan, Kee; Hanchate, Amresh D.; Hernandez, Leilani; Clark, Jack; Gifford, Allen L.] Boston Univ, Boston, MA 02215 USA. [Lai, Mai-Ngan; Groessl, Erik J.; Ho, Samuel B.] Univ Calif San Diego, San Diego, CA 92103 USA. [Asch, Steven] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Chan, Kee; Hanchate, Amresh D.; Hernandez, Leilani; Clark, Jack; Gifford, Allen L.] VA Med Ctr, Boston, MA USA. [Wong, John B.] Tufts Univ, Boston, MA 02111 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 437A EP 438A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002158 ER PT J AU Bunchorntavakul, C Jones, LM Kikuchi, M Valiga, ME Nunes, F Aytaman, A Kaplan, DE Reddy, R Chang, KM AF Bunchorntavakul, Chalermrat Jones, Lisa M. Kikuchi, Masahiro Valiga, Mary E. Nunes, Frederick Aytaman, Ayse Kaplan, David E. Reddy, Rajender Chang, Kyong-Mi TI ACUTE HEPATITIS C: PRESENTATION AND CLINICAL COURSE SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Bunchorntavakul, Chalermrat; Jones, Lisa M.; Kikuchi, Masahiro; Valiga, Mary E.; Nunes, Frederick; Kaplan, David E.; Reddy, Rajender; Chang, Kyong-Mi] Univ Penn, Dept Med, Div Gastroenterol & Hepatol, Philadelphia, PA 19104 USA. [Jones, Lisa M.; Kikuchi, Masahiro; Valiga, Mary E.; Kaplan, David E.; Chang, Kyong-Mi] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Nunes, Frederick] Penn Hosp, Philadelphia, PA 19107 USA. [Aytaman, Ayse] VA New York Harbor Healthcare Syst, Brooklyn, NY USA. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 581A EP 581A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002446 ER PT J AU Kanwal, F Hoang, T Kramer, JR Chrusciel, T El-Serag, H Dominitz, J Asch, S AF Kanwal, Fasiha Hoang, Tuyen Kramer, Jennifer R. Chrusciel, Timothy El-Serag, Hashem Dominitz, Jason Asch, Steven TI EVALUATING QUALITY OF CARE IN PATIENTS WITH HEPATITIS C VIRUS INFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kanwal, Fasiha; Chrusciel, Timothy] St Louis VA Med Ctr, St Louis, MO USA. [Kanwal, Fasiha; Chrusciel, Timothy] St Louis Univ, St Louis, MO 63103 USA. [Hoang, Tuyen] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Kramer, Jennifer R.; El-Serag, Hashem] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Kramer, Jennifer R.; El-Serag, Hashem] Baylor Coll Med, Houston, TX 77030 USA. [Dominitz, Jason] VA Puget Healthcare Syst, Seattle, WA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 591A EP 592A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002467 ER PT J AU Liu, QL Rehman, H Krishnasamy, Y Haque, K Schnellmann, RG Lemasters, JJ Zhong, Z AF Liu, Qinlong Rehman, Hasibur Krishnasamy, Yasodha Haque, Khujista Schnellmann, Rick G. Lemasters, John J. Zhong, Zhi TI AMPHIREGULIN STIMULATES LIVER REGENERATION AFTER SMALL-FOR-SIZE LIVER TRANSPLANTATION IN MICE SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Liu, Qinlong; Rehman, Hasibur; Krishnasamy, Yasodha; Haque, Khujista; Schnellmann, Rick G.; Lemasters, John J.; Zhong, Zhi] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 686A EP 686A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002670 ER PT J AU Golden-Mason, L Bambha, K Cheng, LL Howell, CD Taylor, MW Clark, PJ Afdhal, NH Rosen, HR AF Golden-Mason, Lucy Bambha, Kiran Cheng, Linling Howell, Charles D. Taylor, Milton W. Clark, Paul J. Afdhal, Nezam H. Rosen, Hugo R. TI NK INHIBITORY RECEPTOR EXPRESSION ASSOCIATED WITH TREATMENT FAILURE AND IL-28B GENOTYPE IN PATIENTS WITH CHRONIC HEPATITIS C SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Golden-Mason, Lucy; Bambha, Kiran; Cheng, Linling; Rosen, Hugo R.] Univ Colorado Denver, GI Hepatol, Hepatitis Ctr C, Aurora, CO USA. [Golden-Mason, Lucy] Natl Jewish Hosp, Integrated Program Immunol, Denver, CO USA. [Howell, Charles D.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Taylor, Milton W.] Indiana Univ, Dept Biol, Bloomington, IN USA. [Clark, Paul J.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Afdhal, Nezam H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Rosen, Hugo R.] Denver VA Med Ctr, Denver, CO USA. RI Clark, Paul/A-1480-2012 OI Clark, Paul/0000-0002-1821-4969 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 807A EP 807A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003178 ER PT J AU Li, YH Carpenito, C June, C Kaplan, DE AF Li, Yonghai Carpenito, Carmine June, Carl Kaplan, David E. TI T-CELLS TRANSDUCED WITH HUMAN GLYPICAN-3 SPECIFIC CHIMERIC ANTIGEN RECEPTOR SPECIFICALLY LYSE HEPATOCELLULAR CARCINOMA CELL LINE IN VITRO SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kaplan, David E.] Philadelphia VA Med Ctr, Res Sect, Philadelphia, PA USA. [Li, Yonghai; Kaplan, David E.] Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. [Carpenito, Carmine; June, Carl] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1279A EP 1279A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004411 ER PT J AU Doi, H Kaplan, DE AF Doi, Hiroyoshi Kaplan, David E. TI HUMORAL FACTORS INDUCE B-CELL ACTIVATION IN HCV-RELATED CIRRHOSIS AND ARE ASSOCIATED WITH LOSS OF CD27+MEMORY B-CELLS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kaplan, David E.] Philadelphia VA Med Ctr, Med & Res Sect, Philadelphia, PA USA. [Doi, Hiroyoshi; Kaplan, David E.] Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1321A EP 1321A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004506 ER PT J AU Huang, J Schmeidler, J Beeri, MS West, RK Rosendorff, C Silverman, JM AF Huang, Jennifer Schmeidler, James Beeri, Michal S. West, Rebecca K. Rosendorff, Clive Silverman, Jeremy M. TI Fibrinogen and cognitive function in very old non-demented men SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Letter ID VASCULAR DEMENTIA; DISEASE C1 [Huang, Jennifer; Schmeidler, James; Beeri, Michal S.; West, Rebecca K.; Rosendorff, Clive; Silverman, Jeremy M.] Mt Sinai Sch Med, New York, NY 10029 USA. [Rosendorff, Clive; Silverman, Jeremy M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Huang, J (reprint author), Mt Sinai Sch Med, New York, NY 10029 USA. FU NIA NIH HHS [K01 AG023515, P50-AG05138, P01-AG02219] NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD OCT PY 2011 VL 26 IS 10 BP 1099 EP 1100 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 825NZ UT WOS:000295287100013 PM 21905103 ER PT J AU Keller, PA Harlam, B Loewenstein, G Volpp, KG AF Keller, Punam Anand Harlam, Bari Loewenstein, George Volpp, Kevin G. TI Enhanced active choice: A new method to motivate behavior change SO JOURNAL OF CONSUMER PSYCHOLOGY LA English DT Article DE Choice; Persuasion; Automatic enrollment; Social marketing ID ORGAN DONATION; OPTIMAL DEFAULTS; MANDATED CHOICE; SELF-CONTROL; DECISIONS; RESPONSIBILITY; REGRET; TIME; SATISFACTION; COMMITMENT AB High rates of medication non-adherence have significant public health and economic consequences. In other contexts such as savings behavior, opt-out policies, in which the alternative preferred by the policy maker is made the default, have gotten great traction but may not be feasible in health care settings. After reviewing previous applications, we present a series of studies, including two field experiments, that test the effectiveness of an alternative, 'active choice' policy in which there is no default, but decision makers are required to make a choice (Carroll, Choi, Laibson, Madrian, & Metrick, 2009; Spital, 1993, 1995). In addition, we propose and test a modified version of active choice, that we call 'enhanced active choice' that favors one alternative by highlighting losses incumbent in the in the non-preferred alternative. We recommend Enhanced Active Choice as a complement to automatic enrollment or when automatic enrollment is infeasible or unethical. (C) 2011 Society for Consumer Psychology. Published by Elsevier Inc. All rights reserved. C1 [Keller, Punam Anand] Dartmouth Coll, Tuck Sch Business, Hanover, NH 03755 USA. [Harlam, Bari] CVS Caremark, Woonsocket, RI USA. [Loewenstein, George] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Volpp, Kevin G.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn Wharton Sch, Philadelphia, PA USA. [Volpp, Kevin G.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Keller, PA (reprint author), Dartmouth Coll, Tuck Sch Business, Hanover, NH 03755 USA. EM punam.keller@dartmouth.edu NR 43 TC 27 Z9 27 U1 2 U2 42 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1057-7408 J9 J CONSUM PSYCHOL JI J. Consum. Psychol. PD OCT PY 2011 VL 21 IS 4 SI SI BP 376 EP 383 DI 10.1016/j.jcps.2011.06.003 PG 8 WC Business; Psychology, Applied SC Business & Economics; Psychology GA 834XW UT WOS:000295998800002 ER PT J AU Mathis, KI Wynn, JK Breitmeyer, B Nuechterlein, KH Green, MF AF Mathis, Kristopher I. Wynn, Jonathan K. Breitmeyer, Bruno Nuechterlein, Keith H. Green, Michael F. TI The attentional blink in schizophrenia: Isolating the perception/attention interface SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Schizophrenia; Attentional blink; Attention; Perceptual impairment ID SERIAL VISUAL PRESENTATION; TEMPORAL ATTENTION; QUALITY-ASSURANCE; SELECTION; MECHANISM; DEFICITS; MASKING; MODEL AB Previous work has demonstrated that several aspects of visual processing are impaired in schizophrenia, including early perceptual processes and later higher-order processes. However, it remains unclear whether the stage of processing where early perception and later higher-order processes interact is impaired in schizophrenia. The current research examined this interface in schizophrenia using the attentional blink (AB) paradigm. We administered two rapid serial visual processing (RSVP) tasks to 143 patients with schizophrenia or schizoaffective disorder and 80 healthy controls: 1) a single target detection task, to measure basic visual perception; and 2) a dual target detection task, to measure the AB effect. In the dual target task, the two target stimuli (T1 and T2) were presented at varying positions or "lags" within a rapid sequential stream of distractor stimuli. Participants verbally identified the target stimuli. Both groups showed the expected AB effect, with T2 accuracy being poorest 200-500 ms after presentation of T1. However, patients showed an exaggerated AB effect compared to the healthy controls, with significantly reduced detection of T2, even after correcting for performance on the single target task. The reduction in accuracy was steeper and more pronounced in the patients during the AB lags, and it extended to lags before and after the typical AB. This performance pattern on the AB task suggests that patients with schizophrenia exhibit both deficits in visual processing at the interface of perceptual and attentional processing and a general attentional deficit. Published by Elsevier Ltd. C1 [Mathis, Kristopher I.; Wynn, Jonathan K.; Breitmeyer, Bruno; Nuechterlein, Keith H.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, MIRECC, Los Angeles, CA 90073 USA. RP Mathis, KI (reprint author), VA Greater Los Angeles Healthcare Syst, MIRECC, 11301 Wilshire Blvd,Bldg 210,Room 117, Los Angeles, CA 90073 USA. EM mathis@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU NIH [MH043292, MH065707] FX Funding for this study was provided by NIH Grants MH043292 and MH065707 (MFG); the NIH had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 30 TC 11 Z9 12 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD OCT PY 2011 VL 45 IS 10 BP 1346 EP 1351 DI 10.1016/j.jpsychires.2011.04.002 PG 6 WC Psychiatry SC Psychiatry GA 834XT UT WOS:000295998500010 PM 21550051 ER PT J AU Martin, LF Olincy, A Ross, RG Du, YP Singel, D Shatti, S Tregellas, JR AF Martin, Laura Frances Olincy, Ann Ross, Randy G. Du, Yiping P. Singel, Debra Shatti, Shireen Tregellas, Jason R. TI Cerebellar hyperactivity during smooth pursuit eye movements in bipolar disorder (vol 45, pg 670, 2011) SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Correction C1 [Martin, Laura Frances; Olincy, Ann; Ross, Randy G.; Du, Yiping P.; Singel, Debra; Shatti, Shireen; Tregellas, Jason R.] Univ Colorado Denver Sch Med, Aurora, CO 80045 USA. [Tregellas, Jason R.] Eastern Colorado Hlth Care Syst, Denver Vet Affairs Med Ctr, Res Serv, Denver, CO 80020 USA. RP Martin, LF (reprint author), Univ Colorado Denver Sch Med, Mail Stop F546,13001 E 17th Pl, Aurora, CO 80045 USA. EM laura.martin@ucdenver.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD OCT PY 2011 VL 45 IS 10 BP 1410 EP 1410 DI 10.1016/j.jpsychires.2011.06.004 PG 1 WC Psychiatry SC Psychiatry GA 834XT UT WOS:000295998500020 ER PT J AU Malone, SK AF Malone, Susan Kohl TI Early to Bed, Early to Rise?: An Exploration of Adolescent Sleep Hygiene Practices SO JOURNAL OF SCHOOL NURSING LA English DT Review DE health/wellness; screening/risk identification; high school; integrative reviews ID SCHOOL START TIME; CHILDRENS SLEEP; STUDENTS; PATTERNS; BEHAVIOR; HEALTH; PREVALENCE; QUALITY; IMPACT; AGE AB Cognition, memory, safety, mental health, and weight are all affected by inadequate sleep. Biological studies indicate significant changes in sleep architecture during adolescence, such as changes in melatonin secretion, and a need for greater total sleep time. Yet, social contexts and cultural values impinge on these changing biological sleep needs making adolescents vulnerable to the dangers of insufficient sleep. Sleep hygiene practices are purported as potential mediating factors between biological sleep needs and the sociocultural context of sleep. The purpose of this literature review is to highlight biological and social factors contributing to insufficient sleep in adolescents, to explore the evidence of several recommended sleep hygiene practices, and to stimulate further research about how adolescents negotiate their shifting biological sleep needs amid increasing social demands. C1 Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. RP Malone, SK (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. EM malones@nursing.upenn.edu NR 57 TC 10 Z9 11 U1 2 U2 23 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1059-8405 J9 J SCH NURS JI J. Sch. Nurs. PD OCT PY 2011 VL 27 IS 5 BP 348 EP 354 DI 10.1177/1059840511410434 PG 7 WC Nursing SC Nursing GA 831MI UT WOS:000295734700010 PM 21606219 ER PT J AU Sawyer, AM Canamucio, A Moriarty, H Weaver, TE Richards, KC Kuna, ST AF Sawyer, Amy M. Canamucio, Anne Moriarty, Helene Weaver, Terri E. Richards, Kathy C. Kuna, Samuel T. TI Do cognitive perceptions influence CPAP use? SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Patient compliance; Continuous positive airway pressure; Obstructive sleep apnea; Self efficacy ID OBSTRUCTIVE SLEEP-APNEA; POSITIVE AIRWAY PRESSURE; LONG-TERM COMPLIANCE; NASAL CPAP; ADHERENCE; THERAPY; HEALTH; HYPERTENSION; ASSOCIATION; ADULTS AB Objective: Nonadherence to CPAP increases health and functional risks of obstructive sleep apnea. The study purpose was to examine if disease and treatment cognitive perceptions influence short-term CPAP use. Methods: A prospective longitudinal study included 66, middle-aged (56.7 +/- 10.7 yr) subjects (34 [51.5%] Caucasians; 30 [45.4%] African Americans) with severe OSA (AHI 43.5 events/hr +/- 24.6). Following full-night diagnostic/CPAP polysomnograms, home CPAP use was objectively measured at 1 week and 1 month. The Self Efficacy Measure for Sleep Apnea (SEMSA) questionnaire, measuring risk perception, outcome expectancies, and self-efficacy, was collected at baseline, post-CPAP education, and after 1 week CPAP treatment. Regression models were used. Results: CPAP use at one week was 3.99 +/- 2.48 h/night and 3.06 +/- 2.43 h/night at one month. No baseline SEMSA domains influenced CPAP use. Post-education self-efficacy influenced one week CPAP use (1.52 +/- 0.53, p = 0.007). Self-efficacy measured post-education and after one week CPAP use also influenced one month CPAP (1.40 +/- 0.52, p = 0.009; 1.20 +/- 0.50, p = 0.02, respectively). Conclusion: Cognitive perceptions influence CPAP use, but only within the context of knowledge of CPAP treatment and treatment use. Practice implications: Patient education is important to OSA patients' formulation of accurate and realistic disease and treatment perceptions which influence CPAP adherence. Published by Elsevier Ireland Ltd. C1 [Sawyer, Amy M.] Univ Penn, Sch Nursing, Biobehav Hlth Sci Div, Philadelphia, PA 19104 USA. [Canamucio, Anne] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ & Promot Res, Philadelphia, PA USA. [Sawyer, Amy M.; Kuna, Samuel T.] Univ Penn, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA. [Weaver, Terri E.] Univ Illinois, Coll Nursing, Chicago, IL USA. [Richards, Kathy C.] Univ Penn, Sch Nursing, Ctr Integrat Sci Aging, Philadelphia, PA 19104 USA. [Richards, Kathy C.] Univ Penn, Sch Nursing, Hartford Ctr Geriatr Nursing Excellence, Philadelphia, PA 19104 USA. [Sawyer, Amy M.] Univ Penn, Sch Nursing, Biobehav Res Ctr, Philadelphia, PA 19104 USA. RP Sawyer, AM (reprint author), Univ Penn, Sch Nursing, Biobehav Hlth Sci Div, Claire M Fagin Hall,Rm 307B,418 Curie Blvd, Philadelphia, PA 19104 USA. EM asawyer@nursing.upenn.edu FU VA Stars & Stripes Healthcare Network Competitive Pilot Project Fund (Sawyer); NIH [K99NR011173]; Nursing/Patient Care Services Department at the Philadelphia VA Medical Center; Philips Respironics Sleep, Respironics Foundation; Cephalon FX Research support by VA Stars & Stripes Healthcare Network Competitive Pilot Project Fund (Sawyer) and NIH K99NR011173 (Sawyer). The authors would like to acknowledge the VISN 4 Eastern Regional Sleep Center staff and polysomnography technologists at the Philadelphia VA Medical Center for their diligence in caring for our research patients. We also would like to acknowledge the support of the Nursing/Patient Care Services Department at the Philadelphia VA Medical Center. The study was conducted at the Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania. The University of Pennsylvania IRB and the Philadelphia Veterans Affairs Medical Center IRB approved the study. Drs. Sawyer, Kuna, Moriarty and Richards and Ms Canamucio disclose the absence of financial conflicts of interest. Dr. Weaver has received research support from Philips Respironics Sleep, Respironics Foundation, and Cephalon; consults for Apnex Medical, Inc. and Cephalon, Inc.; receives royalties from Sanofi-Aventis Pharmaceutical, Merck & Co., Inc., Sleep Solutions, N.V. Organon, Apnex Medical, Inc., Ventus Medical, GlaxoSmithKline, Philips Respironics, Cephalon, Inc. NR 33 TC 15 Z9 15 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD OCT PY 2011 VL 85 IS 1 BP 85 EP 91 DI 10.1016/j.pec.2010.10.014 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 829GM UT WOS:000295566600014 PM 21071166 ER PT J AU Olfson, M Ascher-Svanum, H Faries, DE Marcus, SC AF Olfson, Mark Ascher-Svanum, Haya Faries, Douglas E. Marcus, Steven C. TI Predicting Psychiatric Hospital Admission Among Adults With Schizophrenia SO PSYCHIATRIC SERVICES LA English DT Article ID PREVALENCE PSYCHOTIC DISORDERS; MODIFIABLE RISK-FACTORS; TARDIVE-DYSKINESIA; NEGATIVE SYMPTOMS; SUBSTANCE-ABUSE; INSIGHT; REHOSPITALIZATION; RELAPSE; SCALE; PSYCHOPATHOLOGY AB Objective: The authors identified patient characteristics that increased risk of hospital admission among adults with schizophrenia. Methods: A total of 1,460 participants in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) clinical trial were followed from the time they began a randomized trial of medication to first schizophrenia-related hospital admission. Results: In 869 person-years of follow-up, 203 patients were hospitalized. Increased risk of hospital admission was associated with early age (<= 17 years) of first antipsychotic treatment (adjusted hazard ratio [AHR]=2.16, 95% confidence interval [CI]=1.49-3.11), psychiatric hospitalization in past year (AHR=2.99, CI=2.23-4.00), having had DSM-IV alcohol (AHR=1.56, CI=1.16-2.10) or drug (AHR=1.50, CI=1.13-2.00) use disorders in the past five years, and baseline severe symptoms according to the Clinical Global Impressions Scale (AHR=1.54, CI=1.04-2.27), presence of tardive dyskinesia (AHR=1.55, CI=1.07-2.23), a high score on the positive symptoms subscale of the Positive and Negative Syndrome Scale (AHR=1.52, CI=1.07-2.15), and low social function (AHR=1.45, CI=1.03-2.04). As compared with olanzapine, the drugs quetiapine (AHR=2.14, CI=1.39-3.31), perphenazine (AHR=1.80, CI=1.11-2.94), and ziprasidone (AHR=2.70, CI=1.64-4.44) were associated with increased hospitalization risk. Risperidone was associated with a lower hospitalization risk than quetiapine (AHR=1.50, CI=1.01-2.22) and ziprasidone (AHR=1.89, CI=1.19-3.01). Conclusions: Efforts to lower hospital admission risk among individuals with schizophrenia should focus on history of early onset, recent inpatient admission, severe positive symptoms, poor social function, high global illness severity, and comorbid substance use disorders and on selection of an appropriate antipsychotic medication. (Psychiatric Services 62:1138-1145, 2011) C1 [Olfson, Mark] Columbia Univ, Dept Psychiat, New York, NY 10032 USA. [Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Ascher-Svanum, Haya; Faries, Douglas E.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Marcus, Steven C.] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Practice & Policy, Philadelphia, PA 19104 USA. RP Olfson, M (reprint author), Columbia Univ, Dept Psychiat, 1051 Riverside Dr, New York, NY 10032 USA. EM mo49@columbia.edu FU Eli Lilly and Company; Bristol-Myers Squibb FX This project was supported by a research grant from Eli Lilly and Company to Columbia University, for which Dr. Olfson is principal investigator. In addition, Dr. Olfson has received a research grant to Columbia University from Bristol-Myers Squibb, and Dr. Marcus has served as a consultant to Bristol-Myers Squibb. NR 46 TC 24 Z9 24 U1 0 U2 2 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 OCT PY 2011 VL 62 IS 10 BP 1138 EP 1145 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 827WT UT WOS:000295461000006 PM 21969639 ER PT J AU Kim, HM Chiang, C Kales, HC AF Kim, Hyungjin Myra Chiang, Claire Kales, Helen C. TI After the Black Box Warning: Predictors of Psychotropic Treatment Choices for Older Patients With Dementia SO PSYCHIATRIC SERVICES LA English DT Article ID ATYPICAL ANTIPSYCHOTIC MEDICATIONS; PLACEBO-CONTROLLED TRIALS; RISK; DEATH; DEMOGRAPHICS; METAANALYSIS; PREVALENCE; PSYCHOSIS; AMERICANS; MORTALITY AB Objectives: This study aimed to evaluate factors associated with the selection of pharmacological treatments often given as first-line treatments to elderly patients with neuropsychiatric symptoms associated with dementia. It also evaluated patterns of medication usage over time in the year preceding and three years after the U. S. Food and Drug Administration issued a black box warning for antipsychotic usage. Methods: A retrospective cohort consisted of 19,517 Veterans Affairs patients with diagnosed dementia and a new outpatient start with an antipsychotic agent (haloperidol, olanzapine, quetiapine, or risperidone) or valproic acid and its derivatives between May 1, 2004, and September 30, 2008. Patient and facility characteristics were examined for their association with the new starts of these medications. Results: Trends in the rate of fills for psychotropic medications varied, with yearly increases in the use of quetiapine, haloperidol, and valproic acid and decreasing use of olanzapine and risperidone. Predictors of haloperidol use included a new start in nonpsychiatric settings, prior benzodiazepine use, and any prior-year hospitalization. Anxiety disorder and major depression were predictive of not receiving haloperidol. Parkinson's disease was predictive of quetiapine use, whereas bipolar disorder was predictive of valproic acid use. Older age was predictive of use of antipsychotics rather than valproic acid. Urban facilities were less likely to use olanzapine, and significant regional variations were seen. Conclusions: Important patient and facility characteristics were associated with initiating different psychotropic agents among elderly dementia patients. In addition, the rate of use and the factors predictive of use varied across the study years. (Psychiatric Services 62:1207-1214, 2011) C1 [Kim, Hyungjin Myra; Chiang, Claire; Kales, Helen C.] US Dept Vet Affairs, Ann Arbor Ctr Excellence, Serious Mental Illness Treatment Resource & Evalu, Ann Arbor, MI USA. [Chiang, Claire; Kales, Helen C.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Kim, Hyungjin Myra] Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA. RP Kim, HM (reprint author), US Dept Vet Affairs, Ann Arbor Ctr Excellence, Serious Mental Illness Treatment Resource & Evalu, Ann Arbor, MI USA. EM myrakim@umich.edu FU National Institute of Mental Health [R01-MH078698-01] FX This research was supported by grant R01-MH078698-01 from the National Institute of Mental Health. Resources were also contributed by the Serious Mental Illness Treatment, Resource, and Evaluation Center in Ann Arbor. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. The funding organizations had no role in any of the following: design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 21 TC 9 Z9 9 U1 3 U2 6 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 OCT PY 2011 VL 62 IS 10 BP 1207 EP 1214 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 827WT UT WOS:000295461000015 PM 21969648 ER PT J AU Melendez, V Pybus, B Sousa, J Li, Q Caridha, D Collazo, V Olmeda, R Riscoe, M Kelly, J AF Melendez, V. Pybus, B. Sousa, J. Li, Q. Caridha, D. Collazo, V. Olmeda, R. Riscoe, M. Kelly, J. TI Metabolism and disposition of novel liver stage-active acridone antimalarial drugs SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Meeting Abstract C1 [Melendez, V.; Pybus, B.; Sousa, J.; Li, Q.; Caridha, D.; Collazo, V.; Olmeda, R.] Walter Reed Army Inst Res, Silver Spring, MD USA. [Riscoe, M.; Kelly, J.] Portland VA Med Ctr, Portland, OR USA. [Riscoe, M.; Kelly, J.] Portland State Univ, Portland, OR 97207 USA. RI Sousa, Jason/A-9177-2011 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 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD OCT PY 2011 VL 16 SU 1 SI SI BP 145 EP 146 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 828RC UT WOS:000295519100419 ER PT J AU Zavadzkas, JA Mukherjee, R Rivers, WT Patel, RK Meyer, EC Black, LE McKinney, RA Oelsen, JM Stroud, RE Spinale, FG AF Zavadzkas, Juozas A. Mukherjee, Rupak Rivers, William T. Patel, Risha K. Meyer, Evan C. Black, Laurel E. McKinney, Richard A. Oelsen, J. Marshall Stroud, Robert E. Spinale, Francis G. TI Direct regulation of membrane type 1 matrix metalloproteinase following myocardial infarction causes changes in survival, cardiac function, and remodeling SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE myocardial infarction; matrix; myocardial remodeling; ventricular function ID GROWTH-FACTOR-BETA; TGF-BETA; EXTRACELLULAR-MATRIX; RESTRICTED OVEREXPRESSION; BINDING-PROTEINS; ANGIOGENESIS; PROTEOLYSIS; INHIBITION; ACTIVATION; ISCHEMIA AB Zavadzkas JA, Mukherjee R, Rivers WT, Patel RK, Meyer EC, Black LE, McKinney RA, Oelsen JM, Stroud RE, Spinale FG. Direct regulation of membrane type 1 matrix metalloproteinase following myocardial infarction causes changes in survival, cardiac function, and remodeling. Am J Physiol Heart Circ Physiol 301: H1656-H1666, 2011. First published June 10, 2011; doi:10.1152/ajpheart.00141.2011.-The membrane type 1 matrix metalloproteinase (MT1-MMP) is increased in left ventricular (LV) failure. However, the direct effects of altered MT1-MMP levels on survival, LV function, and geometry following myocardial infarction (MI) and the proteolytic substrates involved in this process remain unclear. MI was induced in mice with cardiac-restricted overexpression of MT1-MMP (MT1-MMPexp; full length human), reduced MT1-MMP expression (heterozygous; MT1-MMP(+/-)), and wild type. Post-MI survival was reduced with MT1-MMPexp and increased with MT1-MMP(+/-) compared with WT. LV ejection fraction was lower in the post-MI MT1-MMPexp mice compared with WT post-MI and was higher in the MT1-MMP(+/-) mice. In vivo localization of MT1-MMP using antibody-conjugated microbubbles revealed higher MT1-MMP levels post-MI, which were the highest in the MT1-MMPexp group and the lowest in the MT1-MMP(+/-) group. LV collagen content within the MI region was higher in the MT1-MMPexp vs. WT post-MI and reduced in the MT1-MMP(+/-) group. Furthermore, it was demonstrated that MT1-MMP proteolytically processed the profibrotic molecule, latency-associated transforming growth factor-1-binding protein (LTBP-1), and MT1-MMP-specific LTBP-1 proteolytic activity was increased by over fourfold in the post-MI MT1-MMPexp group and reduced in the MT1-MMP(+/-) group, which was directionally paralleled by phospho-Smad-3 levels, a critical signaling component of the profibrotic transforming growth factor pathway. We conclude that modulating myocardial MT1-MMP levels affected LV function and matrix structure, and a contributory mechanism for these effects is through processing of profibrotic signaling molecules. These findings underscore the diversity of biological effects of certain MMP types on the LV remodeling process. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson Vets Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Rm 625,770 MUSC Complex,114 Doughty St, Charleston, SC 29425 USA. EM wilburnm@musc.edu FU NIH [HL-057952, HL-059165, HL-095608]; Veterans' Affairs Health Administration FX This study was supported by NIH Grants HL-057952, HL-059165, and HL-095608 and by a Merit Award from the Veterans' Affairs Health Administration. NR 29 TC 14 Z9 16 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 OCT PY 2011 VL 301 IS 4 BP H1656 EP H1666 DI 10.1152/ajpheart.00141.2011 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 826NE UT WOS:000295360100048 PM 21666120 ER PT J AU Cronin, J Livhits, M Mercado, C Chen, F Foster, N Chandler, C Gibbons, M Ko, CY Chen, DC AF Cronin, Jennifer Livhits, Masha Mercado, Cheryl Chen, Formosa Foster, Nova Chandler, Charles Gibbons, Melinda Ko, Clifford Y. Chen, David C. TI Quality Improvement Pilot Program for Vulnerable Elderly Surgical Patients SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT 22nd Annual Scientific Meeting of the Southern California Chapter of the American-College-of-Surgeons CY JAN 21-23, 2011 CL Santa Barbara, CA SP Amer Coll Surg ID OLDER-ADULTS; SURGERY; INDICATORS; CARE AB The elderly are a growing surgical population with more comorbidities and less physiological reserve compared with nonelderly patients. The objective of our study was to implement a quality improvement pilot program targeting the specific needs of the elderly. We prospectively enrolled consecutive patients aged 65 years or older undergoing inpatient general or vascular surgery operations. Patients completed a preoperative assessment including the Vulnerable Elder Survey (VES) to determine baseline functional status and incidence of polypharmacy (five or more medications). They were interviewed postdischarge Day 2 and Day 30 for changes in functional status. An intervention was implemented consisting of an elderly-specific postoperative order set and preoperative risk reports sent to the surgical team with instructions to order physical therapy consults and home health nursing on discharge for VES 3 or greater and geriatrics consults for patients with polypharmacy. The elderly-specific order set was used for 71 per cent of the postintervention group. There were no differences in the percentage of participants receiving physical therapy, geriatric, or home health nursing consults between the two groups. The postintervention group had significantly better functional status on postdischarge Day 30 (P < 0.01). Our preliminary data suggest that individualizing care for elderly patients is feasible and may improve postoperative outcomes. C1 [Chen, David C.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Hlth Sci 72 215, Dept Surg, Los Angeles, CA 90095 USA. [Foster, Nova; Chandler, Charles; Chen, David C.] Univ Calif Los Angeles, Dept Surg, Santa Monica, CA USA. [Gibbons, Melinda] Olive View UCLA, Dept Surg, Sylmar, CA USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP Chen, DC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Hlth Sci 72 215, Dept Surg, Box 956904, Los Angeles, CA 90095 USA. EM DCChen@mednet.ucla.edu NR 10 TC 6 Z9 6 U1 1 U2 6 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD OCT PY 2011 VL 77 IS 10 BP 1305 EP 1308 PG 4 WC Surgery SC Surgery GA 829ED UT WOS:000295558600006 PM 22127075 ER PT J AU Walsh, JE Young, MRI AF Walsh, Jarrett E. Young, M. Rita I. TI TGF-beta Regulation of Focal Adhesion Proteins and Motility of Premalignant Oral Lesions via Protein Phosphatase 1 SO ANTICANCER RESEARCH LA English DT Article DE Cytoskeleton; paxillin; phosphatase; PP-1; TGF-beta ID CELL MOTILITY; CANCER-CELLS; PANCREATIC-CANCER; PHOSPHORYLATION; MIGRATION; PAXILLIN; INVASION; SUPPRESSION; COMPLEXES; LINK AB Premalignant oral lesions have a high incidence of recurrence and progression to malignant disease and, although studies have shown the contribution of transforming growth factor beta (TGF-beta) to cancer progression, none have been conducted with premalignant oral lesion cells to determine the impact of TGF-beta in stimulating properties that are characteristic of more invasive cells. The present study focused on TGF-beta-modulation of paxillin and the serine/threonine protein phosphatase PP-I, and the impact on cellular motility. These studies show that TGF-beta stimulates premalignant lesion cell motility and up regulates expression of paxillin, as well as its co-localization with PP-I, while concurrently diminishing the level of paxillin serine phosphorylation. The TGF-beta-mediated up regulation of paxillin and co-localization with actin, as well as the TGF-beta-stimulated motility of premalignant lesion cells, were all blocked by inhibiting PP-I, indicating their dependence on PP-1 activity. These studies suggest interplay between TGF-beta and PP-1 in promoting a more malignant phenotype in premalignant oral lesion cells. C1 [Walsh, Jarrett E.; Young, M. Rita I.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. [Walsh, Jarrett E.; 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 Walsh, JE (reprint author), Ralph H Johnson VA 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 is part of the doctoral dissertation of Jarrett Walsh. 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 22 TC 2 Z9 2 U1 0 U2 2 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD OCT PY 2011 VL 31 IS 10 BP 3159 EP 3164 PG 6 WC Oncology SC Oncology GA 830PA UT WOS:000295667700007 PM 21965722 ER PT J AU Lo, RY Hubbard, AE Shaw, LM Trojanowski, JQ Petersen, RC Aisen, PS Weiner, MW Jagust, WJ AF Lo, Raymond Y. Hubbard, Alan E. Shaw, Leslie M. Trojanowski, John Q. Petersen, Ronald C. Aisen, Paul S. Weiner, Michael W. Jagust, William J. CA Alzheimer's Dis Neuroimaging TI Longitudinal Change of Biomarkers in Cognitive Decline SO ARCHIVES OF NEUROLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; NEUROIMAGING INITIATIVE ADNI; VOXEL-BASED MORPHOMETRY; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; CSF BIOMARKERS; APOLIPOPROTEIN-E; FOLLOW-UP; HIPPOCAMPAL VOLUME; METABOLIC-CHANGES AB Objective: To delineate the trajectories of A beta 42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD). Design: Cohort study. Setting: The 59 study sites for the Alzheimer's Disease Neuroimaging Initiative. Participants: A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007. Main Outcome Measures: Rates of change in level of A beta 42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease's Assessment Scale-cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker. Results: Reductions in the level of A beta 42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of A beta 42 in CSF or FDG uptake. The Alzheimer Disease's Assessment Scale-cognitive subscale scores were related only to the baseline level of A beta 42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD. Conclusion: Trajectories of A beta 42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent. C1 [Lo, Raymond Y.; Hubbard, Alan E.; Jagust, William J.] Univ Calif Berkeley, Div Epidemiol, Berkeley, CA 94720 USA. [Jagust, William J.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Shaw, Leslie M.; Trojanowski, John Q.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Shaw, Leslie M.; Trojanowski, John Q.] Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA. [Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN USA. RP Lo, RY (reprint author), Univ Calif Berkeley, Div Epidemiol, 118 Barker Hall,MC3190, Berkeley, CA 94720 USA. EM rlo@berkeley.edu RI Preda, Adrian /K-8889-2013; Saykin, Andrew/A-1318-2007 OI Preda, Adrian /0000-0003-3373-2438; Saykin, Andrew/0000-0002-1376-8532 FU Pfizer; National Institutes of Health (NIH) [AG024904, U01AG024904, P41 RR023953, R01 AG10897, P01AG19724, P50AG23501, R24 RR021992, R01 NS031966, P01AG012435, AG027859, AG027984, AG 024904, P30 AG010129, K01 AG030514]; National Institute of Neurological Disorders and Stroke [P01 AG 09215-20, P30 AG 10124-18, PO1 AG 17586-10, 1PO1 AG-19724-07, U01 AG 024904-05, P50 NS053488-02, UO1 AG029213-01, RC2NS069368, RC1AG035427, P30AG036468]; Marian S. Ware Alzheimer Program; NIH National Institute on Aging (NIA) [U01 AG 06786, P50 AG 16574, U01 AG 024904, R01 AG11378, U01-AG10483, U01-AG024904, R01-AG030048, R01-AG16381]; Baxter; Neuro-Hitech; Abbott; Martek; Nestle; Kenes International; Merck; Radiopharmaceuticals; US Department of Defense [DAMD17-01-1-0764]; Veterans Administration [MIRECC VISN 21]; State of California; Alzheimer's Association; ADNI NIH [U01 AG024904]; NIA; National Institute of Biomedical Imaging and Bioengineering; Dana Foundation FX Dr Shaw has received funding for travel and speaker honoraria from Pfizer; serves on the editorial board of the journal Therapeutic Drug Monitoring; may potentially receive revenue for patent pending (application number 10/192,193): O-methylated rapamycin derivatives for alleviation and inhibition of lymphoproliferative disorders, licensed by the University of Pennsylvania to Novartis; receives royalties from publication of Applied Pharmacokinetics and Pharmacodynamics: Principles of Therapeutic Drug Monitoring (Wolters Kluwer/Lippincott Williams & Wilkins, 2005); receives research support from the National Institutes of Health (NIH) (grantAG024904[coprincipal investigator {co-PI}, Biomarker Core Laboratory]); and receives board of directors' compensation and holds stock options in Saladax Biomedical. Dr Trojanowski has received funding for travel and honoraria from Takeda to attend numerous conferences not funded by industry; serves as an associate editor of the journal Alzheimer's & Dementia; may accrue revenue on patents regarding Modified Avidin-Biotin Technique, Method of Stabilizing Microtubules to Treat Alzheimer's Disease, Method of Detecting Abnormally Phosphorylated Tau, Method of Screening for Alzheimer's Disease or Disease Associated with the Accumulation of Paired Helical Filaments, Compositions and Methods for Producing and Using Homogeneous Neuronal Cell Transplants, Rat Comprising Straight Filaments in Its Brain, Compositions and Methods for Producing and Using Homogeneous Neuronal Cell Transplants to Treat Neurodegenerative Disorders and Brain and Spinal Cord Injuries, Diagnostic Methods for Alzheimer's Disease by Detection of Multiple MRNAs, Methods and Compositions for Determining Lipid Peroxidation Levels in Oxidant Stress Syndromes and Diseases, Compositions and Methods for Producing and Using Homogenous Neuronal Cell Transplants, Method of Identifying, Diagnosing and Treating alpha-synuclein Positive Neurodegenerative Disorders, Mutation-specific Functional Impairments in Distinct Tau Isoforms of Hereditary Frontotemporal Dementia and Parkinsonism Linked to Chromosome-17: Genotype Predicts Phenotype, Microtubule Stabilizing Therapies for Neurodegenerative Disorders, and Treatment of Alzheimer's and Related Diseases with an Antibody; and receives research support from the NIH National Institute on Aging (NIA) and National Institute of Neurological Disorders and Stroke (grants P01 AG 09215-20 [PI], P30 AG 10124-18 [PI], PO1 AG 17586-10 [project 4 leader], 1PO1 AG-19724-07 [core C leader], U01 AG 024904-05 [coPI, Biomarker Core Laboratory], P50 NS053488-02 [PI], UO1 AG029213-01 [coinvestigator], RC2NS069368 [PI], RC1AG035427 [PI], and P30AG036468 [PI]) and from the Marian S. Ware Alzheimer Program. Dr Petersen serves on scientific advisory boards for Pfizer, Janssen Alzheimer Immunotherapy, Elan, and GE Healthcare; receives royalties from the publication of Mild Cognitive Impairment (Oxford University Press, 2003); and receives research support from the NIH/NIA (grants U01 AG 06786 [PI], P50 AG 16574 [PI], U01 AG 024904 [subcontract PI], and R01 AG11378 [coinvestigator]).; Dr Aisen serves on a scientific advisory board for NeuroPhage; serves as a consultant to Elan, Wyeth, Eisai, Neurochem, Schering-Plough, Bristol-Myers Squibb, Eli Lilly, NeuroPhage, Merck, Roche, Amgen, Genentech, Abbott, Pfizer, Novartis, and Medivation; receives research support from Pfizer, Baxter, Neuro-Hitech, Abbott, Martek, and the NIH/NIA (grants U01-AG10483 [PI], U01-AG024904 [coordinating center director], R01-AG030048 [PI], and R01-AG1381 [coinvestigator]); and has received stock options from Medivation and NeuroPhage. Dr Weiner serves on scientific advisory boards for Bayer Schering Pharma, Eli Lilly, CoMentis, Neurochem, Eisai, Avid, Aegis Therapies, Genentech, Allergan, Lippincott Williams&Wilkins, Bristol-Myers Squibb, Forest Laboratories, Pfizer, McKinsey & Company, Mitsubishi Tanabe Pharma Corporation, and Novartis; has received funding for travel from Nestle and Kenes International to attend conferences not funded by industry; serves on the editorial board of the journal Alzheimer's & Dementia; has received honoraria from the Rotman Research Institute and BOLT International; serves as a consultant for Elan; receives research support from Merck, Radiopharmaceuticals, the NIH (grants U01AG024904 [PI], P41 RR023953 [PI], R01 AG10897 [PI], P01AG19724 [coinvestigator], P50AG23501 [coinvestigator], R24 RR021992 [coinvestigator], R01 NS031966 [coinvestigator], and P01AG012435 [coinvestigator]), the US Department of Defense (DAMD17-01-1-0764 [PI]), the Veterans Administration (MIRECC VISN 21 [core PI]), and the State of California; and holds stock in Synarc and Elan. Dr Jagust has served on a scientific advisory board for Genentech; has served as a consultant for Bayer Healthcare, GE Healthcare, Synarc, Janssen Alzheimer Immunotherapy, Genentech, TauRx, and Merck; and receives research support from the NIH (grants AG027859 [PI], AG027984 [PI], and AG 024904 [coinvestigator]) and the Alzheimer's Association.; Data collection and sharing for this project was funded by ADNI (NIH grant U01 AG024904), which is funded by the NIA and the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca, Bayer Schering Pharma, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly, Medpace, Merck, Novartis, Pfizer, F. Hoffman-La Roche, Schering-Plough, Synarc, as well as 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 (http: //www.fnih.org/). The grantee organization is the Northern California Institute for Research and Education, and our study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. The 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 and K01 AG030514 and the Dana Foundation. NR 40 TC 77 Z9 78 U1 2 U2 13 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 OCT PY 2011 VL 68 IS 10 BP 1257 EP 1266 DI 10.1001/archneurol.2011.123 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 830YV UT WOS:000295696700006 PM 21670386 ER PT J AU Blanquer, J Aspa, J Anzueto, A Ferrer, M Gallego, M Rajas, O Rello, J de Castro, FR Torres, A AF Blanquer, Jose Aspa, Javier Anzueto, Antonio Ferrer, Miguel Gallego, Miguel Rajas, Olga Rello, Jordi Rodriguez de Castro, Felipe Torres, Antonio TI SEPAR Guidelines for Nosocomial Pneumonia SO ARCHIVOS DE BRONCONEUMOLOGIA LA Spanish DT Article ID VENTILATOR-ASSOCIATED PNEUMONIA; HOSPITAL-ACQUIRED PNEUMONIA; INTENSIVE-CARE-UNIT; RANDOMIZED CONTROLLED-TRIAL; C-REACTIVE PROTEIN; REQUIRING MECHANICAL VENTILATION; BRONCHOALVEOLAR LAVAGE FLUID; ANTIBIOTIC-THERAPY; CIRCUIT CHANGES; CRITICALLY-ILL C1 [Blanquer, Jose] Hosp Clin Univ, Unidad Cuidados Intensivos Resp, Valencia, Spain. [Aspa, Javier; Rajas, Olga] Univ Autonoma Madrid, Hosp Univ La Princesa, Madrid, Spain. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. [Ferrer, Miguel; Torres, Antonio] Hosp Clin Barcelona, Unidad Vigilancia Intensiva & Intermedia Resp, Serv Neumol, Inst Torax,IDIBAPS, Barcelona, Spain. [Gallego, Miguel] Corp Sanitaria Parc Tauli, Barcelona, Spain. [Rello, Jordi] VHIR Univ Autonoma Barcelona, UCI, Hosp Univ Vall dHebron, CibeRes, Barcelona, Spain. [Rodriguez de Castro, Felipe] Hosp Univ Gran Canaria Dr Negrin, Las Palmas Gran Canaria, Spain. RP Blanquer, J (reprint author), Hosp Clin Univ, Unidad Cuidados Intensivos Resp, Valencia, Spain. EM blanquer_jos@gva.es OI Rello, Jordi/0000-0003-0676-6210 NR 80 TC 4 Z9 5 U1 1 U2 2 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 0300-2896 EI 1579-2129 J9 ARCH BRONCONEUMOL JI Arch. Bronconeumol. PD OCT PY 2011 VL 47 IS 10 BP 510 EP 520 DI 10.1016/j.arbres.2011.05.013 PG 11 WC Respiratory System SC Respiratory System GA 830OW UT WOS:000295667300006 PM 21908091 ER PT J AU Mathalon, DH AF Mathalon, Daniel H. TI Challenges Associated with Application of Clinical Staging Models to Psychotic Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID RESONANCE-IMAGING MORPHOMETRY; BRAIN; NEUROPLASTICITY; NEUROTOXICITY; SAFER C1 [Mathalon, Daniel H.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA. [Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Mathalon, Daniel H.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. RP Mathalon, DH (reprint author), San Francisco VA Med Ctr, Mental Hlth Serv, 116D,4150 Clement St, San Francisco, CA 94121 USA. EM daniel.mathalon@ucsf.edu OI Mathalon, Daniel/0000-0001-6090-4974 FU NIMH NIH HHS [R01 MH076989, U01 MH082022] NR 11 TC 2 Z9 2 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2011 VL 70 IS 7 BP 600 EP 601 DI 10.1016/j.biopsych.2011.08.007 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 829PI UT WOS:000295595800001 PM 21924130 ER PT J AU Wiren, KM Hashimoto, JG Semirale, AA Zhang, XW AF Wiren, Kristine M. Hashimoto, Joel G. Semirale, Anthony A. Zhang, Xiao-Wei TI Bone vs. fat: Embryonic origin of progenitors determines response to androgen in adipocytes and osteoblasts SO BONE LA English DT Article DE Androgen; Periosteum; Neural crest; Testosterone; Mesenchymal stem cell ID PARIETAL CALVARIAL BONES; SEX STEROIDS; STEM-CELLS; TESTOSTERONE LEVELS; NEURAL CREST; BODY-COMPOSITION; HYPOGONADAL MEN; CERVUS-ELAPHUS; YOUNG MEN; PERIOSTEUM AB Although androgen is considered an anabolic hormone, the consequences of androgen receptor (AR) overexpression in skeletally-targeted AR-transgenic lines highlight the detrimental effect of enhanced androgen sensitivity on cortical bone quality. A compartment-specific anabolic response is observed only in male and not in female AR3.6-transgenic (tg) mice, with increased periosteal bone formation and calvarial thickening. To identify anabolic signaling cascades that have the potential to increase bone formation, qPCR array analysis was employed to define expression differences between AR3.6-tg and wild-type (WT) periosteal tissue. Notably, categories that were significantly different between the two genotypes included axonal guidance, CNS development and negative regulation of Wnt signaling with a node centered on stem cell pathways. Further, fine mapping of AR3.6-tg calvaria revealed that anabolic thickening in vivo is not uniform across the calvaria, occurring only in frontal and in not parietal bones. Multipotent fraction 1 progenitor populations from both genotypes were cultured separately as frontal bone neural crest stem-like cells (fNCSC) and parietal bone mesenchymal stem-like cells (pMSC). Both osteoblastic and adipogenic differentiation in these progenitor populations was influenced by embryonic lineage and by genotype. Adipogenesis was enhanced in WT fNCSC compared to pMSC, but transgenic cultures showed strong suppression of lipid accumulation only in fNCSC cells. Osteoblastogenesis was significantly increased in transgenic fNCSC cultures compared to WT, with elevated alkaline phosphatase (ALP) activity and induction of mineralization and nodule formation assessed by alizarin red and von Kossa staining. Osteocalcin (OC) and ALP mRNA levels were also increased in fNCSC cultures from AR3.6-tg vs. WT, but in pMSC cultures ALP mRNA levels, mineralization and nodule formation were decreased in AR3.6-tg cells. Expression differences identified by array in long bone periosteal tissue from AR3.6-tg vs. WT were recapitulated in the fNCSC samples while pMSC profiles reflected cortical expression. These observations reveal the opposing effects of androgen signaling on lineage commitment and osteoblast differentiation that is enhanced in cells derived from a neural crest origin but inhibited in cells derived from a mesodermal origin, consistent with in vivo compartment-specific responses to androgen. Combined, these results highlight the complex action of androgen in the body that is dependent on the embryonic lineage and developmental origin of the cell. Further, these data these data suggest that the periosteum surrounding long bone is derived from neural crest. Published by Elsevier Inc. C1 [Wiren, Kristine M.; Hashimoto, Joel G.; Semirale, Anthony A.; Zhang, Xiao-Wei] Portland VA Med Ctr, Bone & Mineral Res Unit, Portland, OR USA. [Wiren, Kristine M.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Wiren, Kristine M.; Hashimoto, Joel G.; Semirale, Anthony A.; Zhang, Xiao-Wei] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. RP Wiren, KM (reprint author), Portland VA Med Ctr P3 R&D39, 3710 SW Vet Hosp Rd, Portland, OR 97239 USA. EM wirenk@ohsu.edu OI Wiren, Kristine/0000-0002-6159-4450 FU United States Army Research Acquisition Activity Award [W81XWH-05-1-0086]; National Institute of Diabetes, Digestive Kidney Disease [R01 DK067541]; Veterans Affairs Merit Review Program FX This publication was made possible by grants from the United States Army Research Acquisition Activity Award No. W81XWH-05-1-0086 (KMW) and the National Institute of Diabetes, Digestive & Kidney Disease R01 DK067541 (KMW). KMW is a Research Career Scientist of the Department of Veterans Affairs and received support from the Veterans Affairs Merit Review Program. All work was performed in facilities provided by the Department of Veterans Affairs. The study sponsor(s) did not play a role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. The information contained in this publication does not necessarily reflect the position or the policy of the government, and no official endorsement should be inferred. NR 54 TC 11 Z9 11 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD OCT PY 2011 VL 49 IS 4 BP 662 EP 672 DI 10.1016/j.bone.2011.06.010 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 824ZH UT WOS:000295240200009 PM 21704206 ER PT J AU Eisner, A Luoh, SW AF Eisner, Alvin Luoh, Shiuh-Wen TI Breast Cancer Medications and Vision: Effects of Treatments for Early-stage Disease SO CURRENT EYE RESEARCH LA English DT Review DE Aromatase inhibitor; Dry eye; Estrogen; Retina; Short-wavelength-sensitive cones; Tamoxifen ID ADJUVANT ENDOCRINE THERAPY; ESTROGEN-RECEPTOR MODULATORS; OPEN-ANGLE GLAUCOMA; WAVELENGTH AUTOMATED PERIMETRY; POSTERIOR VITREOUS DETACHMENT; HORMONE REPLACEMENT THERAPY; LATERAL GENICULATE-NUCLEUS; IDIOPATHIC MACULAR HOLES; DUCT STENOSIS SECONDARY; RETINAL BLOOD-FLOW AB This review concerns the effects on vision and the eye of medications prescribed at three phases of treatment for women with early-stage breast cancer (BC): (1) adjuvant cytotoxic chemotherapy, (2) adjuvant endocrine therapy, and (3) symptomatic relief. The most common side effects of cytotoxic chemotherapy are epiphora and ocular surface irritation, which can be caused by any of several different regimens. Most notably, the taxane docetaxel can lead to epiphora by inducing canalicular stenosis. The selective-estrogen-receptor-modulator (SERM) tamoxifen, long the gold-standard adjuvant-endocrine-therapy for women with hormone-receptor-positive BC, increases the risk of posterior subcapsular cataract. Tamoxifen also affects the optic nerve head more often than previously thought, apparently by causing subclinical swelling within the first 2 years of use for women older than similar to 50 years. Tamoxifen retinopathy is rare, but it can cause foveal cystoid spaces that are revealed with spectral-domain optical coherence tomography (OCT) and that may increase the risk for macular holes. Tamoxifen often alters the perceived color of flashed lights detected via short-wavelength-sensitive (SWS) cone response isolated psychophysically; these altered perceptions may reflect a neural-response-sluggishness that becomes evident at similar to 2 years of use. The aromatase inhibitor (AI) anastrozole affects perception similarly, but in an age-dependent manner suggesting that the change of estrogen activity towards lower levels is more important than the low estrogen activity itself. Based on analysis of OCT retinal thickness data, it is likely that anastrozole increases the tractional force between the vitreous and retina. Consequently, AI users, myopic AI users particularly, might be at increased risk for traction-related vision loss. Because bisphosphonates are sometimes prescribed to redress AI-induced bone loss, clinicians should be aware of their potential to cause scleritis and uveitis occasionally. We conclude by suggesting some avenues for future research into the visual and ocular effects of AIs, particularly as relates to assessment of cognitive function. C1 [Eisner, Alvin] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Womens Hlth Res Unit, Portland, OR 97239 USA. [Luoh, Shiuh-Wen] Oregon Hlth & Sci Univ, Knight Canc Inst, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Luoh, Shiuh-Wen] Portland VA Med Ctr, Portland, OR USA. RP Eisner, A (reprint author), Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Womens Hlth Res Unit, Mail Code UHN70, Portland, OR 97239 USA. EM aeisnerphd@gmail.com FU NIH [EY014594] FX Portions of this work were supported by NIH grant EY014594 (to A. Eisner). We would like to thank Alison Conlin, MD, MPH, and David Sullivan, PhD, for critiquing the manuscript; and Linda Simmons, MLS, for help locating references. NR 302 TC 20 Z9 22 U1 1 U2 13 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD OCT PY 2011 VL 36 IS 10 BP 867 EP 885 DI 10.3109/02713683.2011.594202 PG 19 WC Ophthalmology SC Ophthalmology GA 825MX UT WOS:000295283300001 PM 21819259 ER PT J AU Ripoll, LH Triebwasser, J Siever, LJ AF Ripoll, Luis H. Triebwasser, Joseph Siever, Larry J. TI Evidence-based pharmacotherapy for personality disorders SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Review DE Avoidant personality disorder; borderline personality disorder; medication; psychopharmacology; schizotypal personality disorder ID SOCIAL ANXIETY DISORDER; PLACEBO-CONTROLLED-TRIAL; SELF-INJURIOUS-BEHAVIOR; POSITRON-EMISSION-TOMOGRAPHY; 18-MONTH FOLLOW-UP; POSTTRAUMATIC-STRESS-DISORDER; IMPULSIVE AGGRESSIVE-BEHAVIOR; RANDOMIZED CONTROLLED-TRIAL; VENLAFAXINE EXTENDED-RELEASE; FEMALE BORDERLINE-PATIENTS AB Patients with personality disorders are prescribed psychotropic medications with greater frequency than almost any other diagnostic group. Prescribing practices in these populations are often based on anecdotal evidence rather than rigorous data. Although evidence-based psychotherapy remains an integral part of treatment, Axis IT psychopathology is increasingly conceptualized according to neurobiological substrates that correspond to specific psychopharmacological strategies. We summarize the best available evidence regarding medication treatment of personality disordered patients and provide optimal strategies for evidence-based practice. Most available evidence is concentrated around borderline and schizotypal personality disorders, with some additional evidence concerning the treatment of avoidant and antisocial personality disorders. Although maladaptive personality symptoms respond to antidepressants, antipsychotics, mood stabilizers, and other medications, evidence-based pharmacotherapy is most useful in treating circumscribed symptom domains and induces only partial improvement. Most available evidence supports use of medication in reducing impulsivity and aggression, characteristic of borderline and antisocial psychopathology. Efforts have also begun to reduce psychotic-like symptoms and improve cognitive deficits characteristic of schizotypy. Indirect evidence is also provided for psychopharmacological reduction of social anxiety central to avoidant personality disorder. Evidence-based practice requires attention to domains of expected clinical improvement associated with a medication, relative to the potential risks. The development of future rational pharmacotherapy will require increased understanding of the neurobiological underpinnings of personality disorders and their component dimensions. Increasing efforts to translate personality theory and social cognitive neuroscience into increasingly specific neurobiological substrates may provide more effective targets for pharmacotherapy. C1 [Ripoll, Luis H.; Triebwasser, Joseph; Siever, Larry J.] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY 10468 USA. RP Ripoll, LH (reprint author), James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Luis.Ripoll@mssm.edu NR 185 TC 11 Z9 11 U1 7 U2 30 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD OCT PY 2011 VL 14 IS 9 BP 1257 EP 1288 DI 10.1017/51461145711000071 PG 32 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 827NG UT WOS:000295434600010 PM 21320390 ER PT J AU Shen, Q Du, F Huang, SL Duong, TQ AF Shen, Qiang Du, Fang Huang, Shiliang Duong, Timothy Q. TI Spatiotemporal characteristics of postischemic hyperperfusion with respect to changes in T1, T2, diffusion, angiography, and blood-brain barrier permeability SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ADC; arterial spin labeling; CBF; cerebral ischemia; dynamic susceptibility-contrast; relaxation time ID CEREBRAL-ARTERY OCCLUSION; QUANTITATIVE DIFFUSION; ISCHEMIC STROKE; FOCAL ISCHEMIA; PERFUSION; TISSUE; REPERFUSION; RATS; MRI; FLOW AB The spatiotemporal dynamics of postischemic hyperperfusion (HP) remains incompletely understood. Diffusion, perfusion, T2, T1, angiographic, dynamic susceptibility-contrast magnetic resonance imaging (MRI) and magnetic resonance angiography were acquired longitudinally at multiple time points up to 7 days after stroke in rats subjected to 30-, 60-, and 90-minutes middle cerebral artery occlusion (MCAO). The spatiotemporal dynamics of postischemic HP was analyzed and compared with T1, T2 and blood-brain barrier (BBB) changes. No early HP within 3 hours after recanalization was observed. Late (>= 12 hours) HP was present in all animals of the 30-minute MCAO group (N = 20), half of the animals in the 60-minute MCAO group (N = 8), and absent in the 90-minute MCAO group (N = 9). Dynamic susceptibility-contrast MRI and magnetic resonance angiography corroborated HP. Hyperperfusion preceded T2 increase in some animals, but HP and T2 changes temporally coincided in others. T2 peaked first at 24 hours whereas HP peaked at 48 hours after occlusion, and HP resolved by day 7 in most animals at which point the arteries became tortuous. Pixel-by-pixel tracking analysis showed that tissue did not infarct (migrated from core or mismatch at 30 minutes to normal at 48 hours) showed normal cerebral blood flow (CBF), whereas infarct tissue (migrated from core or mismatch at 30 minutes to infarct at 48 hours) showed exaggerated CBF, indicating that HP was associated with poor outcome. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 2076-2085; doi:10.1038/jcbfm.2011.64; published online 4 May 2011 C1 [Shen, Qiang; Du, Fang; Huang, Shiliang; 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, 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 40 TC 23 Z9 23 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2011 VL 31 IS 10 BP 2076 EP 2085 DI 10.1038/jcbfm.2011.64 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 829YB UT WOS:000295621600012 PM 21540871 ER PT J AU Vermehren, J Yu, ML Monto, A Yao, JD Anderson, C Bertuzis, R Schneider, G Sarrazin, C AF Vermehren, Johannes Yu, Ming-Lung Monto, Alexander Yao, Joseph D. Anderson, Christopher Bertuzis, Rasa Schneider, George Sarrazin, Christoph TI Multi-center evaluation of the Abbott RealTime HCV Assay for monitoring patients undergoing antiviral therapy for chronic hepatitis C SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE Chronic hepatitis C; Pegylated interferon; Ribavirin; RealTime HCV; bDNA; TMA; Rapid virologic response; Early virologic response; Response-guided therapy ID RAPID VIROLOGICAL RESPONSE; COBAS AMPLIPREP/COBAS TAQMAN; VIRUS-RNA QUANTIFICATION; ALPHA-2A PLUS RIBAVIRIN; TIME PCR ASSAYS; QUANTITATIVE DETECTION; GENOTYPE-1 PATIENTS; TREATMENT DURATION; MANAGEMENT; INFECTION AB Background: Hepatitis C virus (HCV) RNA monitoring during antiviral therapy is essential for early prediction of treatment success and failure to peginterferon alfa/ribavirin (PEG-IFN/RBV) therapy. Objectives: In this multi-center study we assessed the clinical utility of the Abbott RealTime HCV assay for monitoring patients undergoing antiviral therapy for chronic infection with HCV genotypes (GT) 1-3. Study design: We analyzed serum from 361 patients with chronic hepatitis C who had been treated with PEG-IFN/RBV. The predictive value of rapid virologic response (RVR), partial (>= 2log(10) decline) and complete (HCV-RNA undetectable) early virologic response (pEVR/cEVR) based on RealTime HCV for achieving sustained virologic response was evaluated. In addition, the utility of RealTime HCV to tailor treatment duration according to individual virologic responses was studied in a subset of 136 GT 1 patients and compared to the reference tests, Versant HCV Quantitative 3.0 (bDNA) and Qualitative (TMA) assay. Results: At week 4 of therapy, patients with RVR had a 100% and 93.5% probability to achieve an SVR in GT 1 and GT 2/3 patients, respectively. At week 12, patients who did not achieve a pEVR had a 97.2% and 100% probability of not achieving an SVR. In addition, assignment of GT 1 patients to abbreviated or extended treatment durations based on low baseline HCV-RNA (<800,000 IU/mL) and RVR or pEVR was highly concordant between RealTime HCV and bDNA/TMA assays (97.8% and 91.9%, respectively). Conclusions: The RealTime HCV assay is suitable for monitoring virologic response to PEG-INF/RBV therapy and tailoring treatment duration accordingly. (C) 2011 Elsevier B. V. All rights reserved. C1 [Vermehren, Johannes; Sarrazin, Christoph] Klinikum JW Goethe Univ, Med Klin 1, Frankfurt, Germany. [Yu, Ming-Lung] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Kaohsiung Municipal Ta Tung Hosp, Dept Internal Med, Kaohsiung, Taiwan. [Monto, Alexander] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Yao, Joseph D.] Mayo Clin, Mayo Med Labs, Rochester, MN USA. [Anderson, Christopher; Bertuzis, Rasa; Schneider, George] Abbott Mol, Des Plaines, IL USA. RP Sarrazin, C (reprint author), Klinikum JW Goethe Univ, Med Klin 1, Frankfurt, Germany. EM sarrazin@em.uni-frankfurt.de FU Abbott Molecular FX MLY, AM, JDY and CS have received research grants from Abbott Molecular. CA, RB and GS are employees of Abbott Molecular. NR 31 TC 40 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD OCT PY 2011 VL 52 IS 2 BP 133 EP 137 DI 10.1016/j.jcv.2011.07.007 PG 5 WC Virology SC Virology GA 828WS UT WOS:000295535500014 PM 21803650 ER PT J AU Moreno, K Murray-Wijelath, J Yagi, M Kohler, T Hatsukami, T Clowes, A Sobel, M AF Moreno, Katherine Murray-Wijelath, Jacqui Yagi, Mayumi Kohler, Ted Hatsukami, Thomas Clowes, Alexander Sobel, Michael TI Circulating inflammatory cells are associated with vein graft stenosis SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; GLYCOPROTEIN IB-ALPHA; SURFACE P-SELECTIN; BYPASS-SURGERY; PLATELET ACTIVATION; NEOINTIMA FORMATION; NATURAL-HISTORY; VASCULAR INJURY; INTEGRIN MAC-1; RESTENOSIS AB Objective: Infrainguinal autogenous vein grafts are especially prone to narrowing and failure, and both inflammatory and thrombotic pathways are implicated. Platelets and monocytes are the key thrombo-inflammatory cells that arrive first at sites of vascular injury. These cells have potent interactions that recruit and activate one another, propagating thrombotic and inflammatory responses within the vessel wall. We therefore hypothesized that elevated levels of platelet-monocyte aggregates (PMA) might be associated with stenosis, and could possibly discriminate between patients with or without vein graft stenosis. Methods: Thirty-six vascular surgery patients were studied, in a stable quiescent period after infrainguinal autogenous vein graft bypasses for occlusive disease. Eighteen patients had hemodynainically significant graft stenoses confirmed by imaging, and 18 were free from stenosis. The level of PMA in whole blood was quantified after blood draw using two-color flow cytometry. Three measurements were made per sample: the basal, in-vivo level of aggregates (baseline PMA); the predisposition to spontaneously generate PMA (spontaneous PMA); and PMA generation by the addition of exogenous thrombin receptor-activating peptide (stimulated PMA). The baseline, in-vivo level of PMA was estimated by immediate flow analysis. The predisposition to spontaneously generate PMA was measured after in vitro incubation. Responsiveness to thrombin stimulation of the blood was quantified by the in vitro dose response to an exogenous thrombin receptor-activating peptide (sfllrn). Results: Baseline PMA levels were similar in patients with vein graft stenosis vs nonstenosis (14.8% +/- 3.2 vs 10.1% +/- 1.5, respectively, mean +/- SEM). However, patients with stenosis showed higher spontaneous PMA levels (58.5% +/- 4.5 vs 28.3% +/- 4.3; P < .001) and higher stimulated PMA levels (P < .001; analysis of variance). Covariables of smoking, diabetes, statin, or antithrombotic therapy could not account for these differences. Conclusions: Platelet-monocyte reactivity may play a role in the development of vein graft stenoses. Those with/without stenosis differed primarily in their threshold, or predisposition to form aggregates (spontaneous PMA), while their basal circulating levels of PMA (baseline PMA) were similar. These measurements may unmask pathologic differences in thrombo-inflammatory responsiveness that are not apparent in basal measurements. Understanding the causes and mechanisms leading to abnormal platelet-monocyte responses may improve approaches to predicting or preventing vein graft stenosis. (J Vase Surg 2011;54:1124-30.) Clinical Relevance: Infrainguinal autogenous vein grafts are especially prone to narrowing and failure with both inflammatory and thrombotic pathways implicated. Platelets and monocytes are key thrombo-inflammatory cells that arrive first at sites of vascular injury. These cells have potent interactions that recruit and activate one another, propagating thrombotic and inflammatory responses within the vessel wall. Excessive platelet-monocyte interactions are associated with myocardial infarction, unstable coronary syndrome, and cerebral vascular accidents. This article bridges clinical and basic science. It has a potentially large clinical impact in that it could lead to development of methods that identify patients who have increased risk of graft failure and provide clues that help with the design of drugs that limit thrombo-inflammatory processes that lead to graft failure. C1 VA Puget Sound Hlth Care Syst, Div Vasc Surg, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Moreno, K (reprint author), 1660 S Columbian Way,Bldg 1,Room 605, Seattle, WA 98108 USA. EM morenok@u.washington.edu FU US Department of Veterans Affairs, Office of Research and Development, Merit Review Agency; National Heart, Lung, and Blood Institute [T32 HL007828] FX Supported by a grant from the US Department of Veterans Affairs, Office of Research and Development, Merit Review Agency (M.S., T.K., T.H.), and National Heart, Lung, and Blood Institute, T32 HL007828 (K.M.). NR 44 TC 5 Z9 5 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2011 VL 54 IS 4 BP 1124 EP 1130 DI 10.1016/j.jvs.2011.04.039 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 829FA UT WOS:000295562800027 PM 21906902 ER PT J AU Resnik, L Reiber, G Evans, R Steager, P Barnabe, K AF Resnik, Linda Reiber, Gayle Evans, Rachel Steager, Pam Barnabe, Kate TI New Guidebook to Facilitate VA/DoD Collaboration in Health Care Research SO MILITARY MEDICINE LA English DT Editorial Material C1 [Resnik, Linda; Steager, Pam; Barnabe, Kate] Providence VA Med Ctr, Providence, RI 02908 USA. [Resnik, Linda] Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA. [Reiber, Gayle] US Dept Vet Affairs, VA Puget Sound Healthcare Syst, Washington, DC 20420 USA. [Reiber, Gayle] Univ Washington, Seattle, WA 98195 USA. [Evans, Rachel] Brooke Army Med Ctr, Ctr Intrepid, Ft Sam Houston, TX 78234 USA. RP Resnik, L (reprint author), Providence VA Med Ctr, 830 Chalkstone Ave, Providence, RI 02908 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 2011 VL 176 IS 10 BP 1085 EP 1087 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 831EK UT WOS:000295711300001 PM 22128638 ER PT J AU Blackwell, T Yaffe, K Ancoli-Israel, S Redline, S Ensrud, KE Stefanick, ML Laffan, A Stone, KL AF Blackwell, Terri Yaffe, Kristine Ancoli-Israel, Sonia Redline, Susan Ensrud, Kristine E. Stefanick, Marcia L. Laffan, Alison Stone, Katie L. CA Osteoporotic Fractures Men MrOS St TI Association of Sleep Characteristics and Cognition in Older Community-Dwelling Men: the MrOS Sleep Study SO SLEEP LA English DT Article DE Sleep fragmentation; total sleep time; cognitive function; aging ID OSTEOPOROTIC FRACTURES; DAYTIME SLEEPINESS; APNEA SYNDROME; PERFORMANCE; QUALITY; ADULTS; SCALE; IMPAIRMENT; ACTIGRAPHY; INSOMNIA AB Study Objectives: To examine the association of objectively and subjectively measured sleep characteristics with cognition in older men. Design: A population-based cross-sectional study. Setting: 6 centers in the United States. Participants: 3,132 community-dwelling older men (mean age 76.4 +/- 5.6 years). Interventions: None. Measurements and Results: Objectively measured sleep predictors from wrist actigraphy were total sleep time (TST), sleep efficiency (SE), and wake after sleep onset (WASO). Subjective sleep predictors were self-reported poor sleep (Pittsburgh Sleep Quality Index [PSQI] > 5), excessive daytime sleepiness (EDS, Epworth Sleepiness Scale Score > 10), and TST. Cognitive outcomes were measured with the Modified Mini-Mental State examination (3MS), the Trails B test, and the Digit Vigilance Test (DVT). After adjustment for multiple potential confounders, WASO was modestly related to poorer cognition. Compared to those with WASO < 90 min, men with WASO >= 90 min took 6.1 sec longer to complete the Trails B test and had a 0.9-point worse 3MS score, on average (P < 0.05). Actigraphically measured long sleepers had a slightly worse 3MS score compared to those with 7-8 h of sleep, but had similar Trails B and DVT completion times. Compared to those who self-reported sleeping 7-8 h, long sleepers (> 8 h) on average took 8.6 sec more to complete the Trails B test, had a 0.6-point worse 3MS score, and took 46 sec longer to complete the DVT (P < 0.05). PSQI and ED S were not independently related to cognitive outcomes. Conclusions: There were modest cross-sectional associations of WASO and self-reported long sleep with cognition among older community-dwelling men. ED S and PSQI were not related to cognition. C1 [Blackwell, Terri; Laffan, Alison; Stone, Katie L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Redline, Susan] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Ensrud, Kristine E.] Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Stefanick, Marcia L.] Stanford Univ, Dept Med, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. RP Blackwell, T (reprint author), San Francisco Coordinating Ctr, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA. EM tblackwell@sfcc-cpmc.net FU Sepracor; Litebook; Dymedix, Inc. FX This was not an industry supported study. Dr. Ancoli-Israel has consulted for or is on the advisory boards of Ferring Pharmaceuticals, GlaxoSmithKline, Merck, NeuroVigil, Pfizer, Philips Respironics, Sanofi-Aventis, Sepracor, Scherling-Plough, and Perdue and has received research support from Sepracor and Litebook. Dr. Redline is the incumbent of an endowed chair professorship donated to Harvard Medical School by Dr. Peter Farrell, the founder and board chairman of ResMed, Inc, has received research support from Dymedix, Inc, and has received equipment for use in research from Philips Respironics. The other authors have indicated no financial conflicts of interest. NR 45 TC 54 Z9 55 U1 1 U2 5 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD OCT 1 PY 2011 VL 34 IS 10 BP 1347 EP 1356 DI 10.5665/SLEEP.1276 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 829ZC UT WOS:000295624800011 PM 21966066 ER PT J AU Maust, DT Mavandadi, S Eakin, A Streim, JE DiFillipo, S Snedden, T Oslin, DW AF Maust, Donovan T. Mavandadi, Shahrzad Eakin, April Streim, Joel E. DiFillipo, Suzanne Snedden, Thomas Oslin, David W. TI Telephone-Based Behavioral Health Assessment for Older Adults Starting a New Psychiatric Medication SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; LATE-LIFE DEPRESSION; PRIMARY-CARE; ANTIDEPRESSANT PHARMACOTHERAPY; PSYCHOTROPIC MEDICATIONS; ANXIETY DISORDERS; OFFICE VISITS; UNITED-STATES; DSM-IV AB Objectives: The purpose of this study is to explore behavioral health symptoms and characteristics of noninstitutionalized older adults newly started on an antidepressant, anxiolytic, or antipsychotic agent by nonpsychiatrist physicians. Design: Naturalistic cohort study of older adults participating in the Pharmaceutical Assistance Contract for the Elderly (PACE) of the state of Pennsylvania. Setting/Participants: Noninstitutionalized adults in Pennsylvania. Measurements: Standardized scales including the Blessed Orientation-Memory-Concentration (BOMC) test, Mini International Neuropsychiatric Interview (including Psychosis, Mania, Generalized Anxiety Disorder [GAD], Panic Disorder, and Alcohol Abuse/Dependence modules), Patient Health Questionnaire-9 (PHQ-9), Paykel Scale for suicide ideation, and Medical Outcomes Survey (SF-12). Results: Participants were mostly women (83.7%) with a mean age of 79.2 years (SD 7.1). The average PHQ-9 score for those on antidepressants was 5.8 (5.2), with no statistically significant difference between medication groups (F-[2,F-409] = 1.48, p = 0.23); just seven (4.9%) of those receiving anxiolytics met criteria for an anxiety disorder, which was not significantly different than other medication classes (chi(2) (2) = 0.83, p = 0.66). Overall, 197 (47.8%) of the sample did not meet criteria for a mental health disorder. Just 69 (28.8%) of those on antidepressants reported depression as the self-reported reason for taking the medication, while 91 (22.8%) of the total reported poor sleep or stressful life events as the reason. Conclusions: In this sample, many older persons received psychotropic medications despite low symptomatology, increasing the costs of care and possible exposure to unnecessary side effects. It is important to understand perceived benefit to both patient and provider of such prescribing patterns and work towards minimizing unnecessary use. (Am J Geriatr Psychiatry 2011; 19: 851-858) C1 [Maust, Donovan T.; Mavandadi, Shahrzad; Eakin, April; Streim, Joel E.; DiFillipo, Suzanne; Oslin, David W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Mavandadi, Shahrzad; Streim, Joel E.; DiFillipo, Suzanne; Oslin, David W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Mavandadi, Shahrzad; Streim, Joel E.; DiFillipo, Suzanne; Oslin, David W.] VISN 4 Mental Illness Res Educ & Clin Ctr MIRECC, Philadelphia, PA USA. [Snedden, Thomas] Penn Dept Aging, PACE Program, Harrisburg, PA USA. RP Maust, DT (reprint author), Univ Penn, Dept Psychiat, 3535 Market St,2nd Floor, Philadelphia, PA 19104 USA. EM Donovan.Maust@uphs.upenn.edu FU Pennsylvania Department of Aging; NIMH; Department of Psychiatry, University of Pennsylvania FX This work was funded by the PACE Program of the Pennsylvania Department of Aging. DTM is supported by the NIMH-funded Clinical Research Scholars Program of the Department of Psychiatry, University of Pennsylvania. NR 37 TC 12 Z9 12 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD OCT PY 2011 VL 19 IS 10 BP 851 EP 858 DI 10.1097/JGP.0b013e318202c1dc PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 823XN UT WOS:000295161400003 PM 21946801 ER PT J AU Fett, NM Toporcer, MB Dalmau, J Shinohara, MM Vogl, DT AF Fett, Nicole M. Toporcer, Mary B. Dalmau, Josep Shinohara, Michi M. Vogl, Dan T. TI Scleromyxedema and dermato-neuro syndrome in a patient with multiple myeloma effectively treated with dexamethasone and bortezomib SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID PAPULAR MUCINOSIS; THALIDOMIDE; THERAPY C1 [Fett, Nicole M.] Univ Penn, Perelman Ctr Adv Med, Dept Dermatol, Sch Med, Philadelphia, PA 19104 USA. [Fett, Nicole M.] Philadelphia VA Med Ctr, Dept Med, Div Dermatol, Philadelphia, PA USA. [Toporcer, Mary B.] Doylestown Dermatol, Doylestown, PA USA. [Dalmau, Josep] Univ Penn, Dept Neurol, Sch Med, Philadelphia, PA 19104 USA. [Shinohara, Michi M.] Univ Penn, Dept Dermatopathol, Sch Med, Philadelphia, PA 19104 USA. [Vogl, Dan T.] Univ Penn, Div Hematol & Oncol, Dept Med, Sch Med, Philadelphia, PA 19104 USA. RP Fett, NM (reprint author), Univ Penn, Perelman Ctr Adv Med, Dept Dermatol, Sch Med, Suite 1 330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM nicole.fett@uphs.upenn.edu OI Vogl, Dan/0000-0002-2935-2566; Dalmau, Josep/0000-0001-5856-2813 NR 19 TC 12 Z9 12 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD OCT PY 2011 VL 86 IS 10 BP 893 EP 896 DI 10.1002/ajh.22131 PG 4 WC Hematology SC Hematology GA 824WB UT WOS:000295231800022 PM 22026006 ER PT J AU Lieu, TA Au, D Krishnan, JA Moss, M Selker, H Harabin, A Taggart, V Connors, A AF Lieu, Tracy A. Au, David Krishnan, Jerry A. Moss, Marc Selker, Harry Harabin, Andrea Taggart, Virginia Connors, Alfred CA Comparative Effectiveness Res Lung TI Comparative Effectiveness Research in Lung Diseases and Sleep Disorders Recommendations from the National Heart, Lung, and Blood Institute Workshop SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE randomized controlled trials; observational studies; implementation; study designs; methodology ID UNITED-STATES; TIME-SERIES; CARE; SAFETY; NETWORK; ASTHMA; TRIAL AB The Division of Lung Diseases of the National Heart, Lung, and Blood Institute (NHLBI) held a workshop to develop recommendations on topics, methodologies, and resources for comparative effectiveness research (CER) that will guide clinical decision making about available treatment options for lung diseases and sleep disorders. A multidisciplinary group of experts with experience in efficacy, effectiveness, implementation, and economic research identified (a) what types of studies the domain of CER in lung diseases and sleep disorders should include, (b) the criteria and process for setting priorities, and (c) current resources for and barriers to CER in lung diseases. Key recommendations were to (1) increase efforts to engage stakeholders in developing CER questions and study designs; (2) invest in further development of databases and other infrastructure, including efficient methods for data sharing; (3) make full use of a broad range of study designs; (4) increase the appropriate use of observational designs and the support of methodologic research; (5) ensure that committees that review CER grant applications include persons with appropriate perspective and expertise; and (6) further develop the workforce for CER by supporting training opportunities that focus on the methodologic and practical skills needed. C1 [Harabin, Andrea; Taggart, Virginia] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. [Connors, Alfred] Case Western Reserve Univ, Sch Med, Metrohlth Med Ctr, Cleveland, OH USA. [Lieu, Tracy A.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Lieu, Tracy A.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Lieu, Tracy A.] Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. [Au, David] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Au, David] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Au, David] Dept Vet Affairs, Seattle, WA USA. [Krishnan, Jerry A.] Univ Chicago, Dept Med, Asthma & COPD Ctr, Chicago, IL 60637 USA. [Krishnan, Jerry A.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Moss, Marc] Univ Colorado, Sch Med, Dept Med, Denver, CO USA. [Selker, Harry] Tufts Univ, Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Clin & Translat Sci Inst, Boston, MA 02111 USA. RP Taggart, V (reprint author), NHLBI, Div Lung Dis, NIH, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM taggartv@nih.gov FU Division of Lung Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health; HSR&D, VA Puget Sound Health Care System FX Supported by the Division of Lung Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health.; D.A. was funded by HSR&D, VA Puget Sound Health Care System. The views expressed in this manuscript are those of the authors and do not necessarily represent the opinions of the Department of Veterans Affairs. NR 42 TC 23 Z9 24 U1 1 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 OCT 1 PY 2011 VL 184 IS 7 BP 848 EP 856 DI 10.1164/rccm.201104-0634WS PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 827DM UT WOS:000295407300020 PM 21965016 ER PT J AU Hsia, RY Asch, SM Weiss, RE Zingmond, D Liang, L Han, W McCreath, H Sun, BC AF Hsia, R. Y. Asch, S. M. Weiss, R. E. Zingmond, D. Liang, L. Han, W. McCreath, H. Sun, B. C. TI Is Ambulance Diversion Associated With Increased Mortality for Emergency Department Patients Who Are Admitted? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Annual Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2011 CL San Francisco, CA SP Amer Coll Emergency Phys C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. VA Greater Los Angeles Hlth Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2011 VL 58 IS 4 SU S BP S181 EP S181 PG 1 WC Emergency Medicine SC Emergency Medicine GA 827ID UT WOS:000295421300012 ER PT J AU Singh, JA Houston, TK Ponce, BA Maddox, G Bishop, MJ Richman, J Campagna, EJ Henderson, WG Hawn, MT AF Singh, Jasvinder A. Houston, Thomas K. Ponce, Brent A. Maddox, Grady Bishop, Michael J. Richman, Joshua Campagna, Elizabeth J. Henderson, William G. Hawn, Mary T. TI Smoking As a Risk Factor for Short-Term Outcomes Following Primary Total Hip and Total Knee Replacement in Veterans SO ARTHRITIS CARE & RESEARCH LA English DT Article ID POSTOPERATIVE PULMONARY COMPLICATIONS; QUALITY IMPROVEMENT PROGRAM; SURGEON PROCEDURE VOLUME; BODY-MASS INDEX; CIGARETTE-SMOKE; UNITED-STATES; GENERAL-ANESTHESIA; ABDOMINAL-SURGERY; WOUND-INFECTION; SURGICAL CARE AB Objective. To assess the effect of smoking on postoperative complications following elective primary total hip replacement (THR) or primary total knee replacement (TKR). Methods. We used data from the national Veterans Affairs Surgical Quality Improvement Program to examine the association of smoking status at surgery with 30-day postoperative complication rates (including surgical site and other infections, pneumonia, stroke, myocardial infarction, mortality, and other complications) in veterans undergoing primary elective THR or TKR. Multilevel multivariable-adjusted logistic regression models, adjusted for age, race/ethnicity, work relative value units, American Society of Anesthesiology classification, and year of surgery, with additional adjustment for wound classification for surgical site infections, were used. Results. A total of 33,336 patients, 95% men and 80% white with a mean age of 64 years, underwent elective primary THR/TKR between October 2001 and September 2008. Fifty-seven percent never smoked, 19% were prior smokers, and 24% were current smokers. Current smokers undergoing THR/TKR were significantly more likely than never smokers to have surgical site infections (odds ratio [OR] 1.41, 95% CI 1.16-1.72), pneumonia (OR 1.53, 95% CI 1.10-2.14), stroke (OR 2.61, 95% CI 1.26-5.41), and 1-year mortality (OR 1.63, 95% CI 1.31-2.02). Prior smokers were significantly more likely than nonsmokers to have pneumonia, (OR 1.34, 95% CI 1.00-1.80), stroke (OR 2.14, 95% CI 1.12-4.10), and urinary tract infection (OR 1.26, 95% CI 1.02-1.55). Conclusion. Current smoking at the time of elective THR or TKR is associated with increased postarthroplasty complications, especially surgical site infections and pneumonia. Preoperative smoking cessation programs should be considered in patients undergoing elective THR or TKR. C1 [Singh, Jasvinder A.; Ponce, Brent A.; Maddox, Grady; Richman, Joshua; Hawn, Mary T.] Univ Alabama, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Ponce, Brent A.; Maddox, Grady; Richman, Joshua; Hawn, Mary T.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Rochester, MN USA. [Houston, Thomas K.] Bedford VA Med Ctr, Bedford, MA USA. [Bishop, Michael J.] VA Cent Off, Washington, DC USA. [Bishop, Michael J.] VA Puget Sound, Seattle, WA USA. [Bishop, Michael J.] Univ Washington, Sch Med, Seattle, WA USA. [Campagna, Elizabeth J.; Henderson, William G.] Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. [Henderson, William G.] Denver VA Med Ctr, Aurora, CO 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 RI Houston, Thomas/F-2469-2013 OI singh, jasvinder/0000-0003-3485-0006 FU VA [IIR IAB 06-038-2]; Allergan; Takeda; Savient; Wyeth; Amgen FX Supported by the VA (grant IIR IAB 06-038-2) and the use and resources of facilities at the Department of VA Medical Centers at Bedford, Massachusetts, Birmingham, Alabama, and Puget Sound, Washington.; Mr. Singh has received consultant fees, speaking fees, and/or honoraria (less than $ 10,000 each) from Savient, Novartis, Takeda, URL Pharmaceuticals, and Abbott, and has received research and travel grants from Allergan, Takeda, Savient, Wyeth, and Amgen. Dr. Ponce has received consultant fees, speaking fees, and/or honoraria (less than $ 10,000) from Arinex and (more than $ 10,000) from Tornier. NR 54 TC 31 Z9 31 U1 0 U2 3 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 OCT PY 2011 VL 63 IS 10 BP 1365 EP 1374 DI 10.1002/acr.20555 PG 10 WC Rheumatology SC Rheumatology GA 825FA UT WOS:000295255200002 PM 21770042 ER PT J AU Singh, JA Lewallen, DG AF Singh, Jasvinder A. Lewallen, David G. TI Association of Peptic Ulcer Disease and Pulmonary Disease With Risk of Periprosthetic Fracture After Primary Total Knee Arthroplasty SO ARTHRITIS CARE & RESEARCH LA English DT Article ID TOTAL HIP-ARTHROPLASTY; SUPRACONDYLAR FRACTURES; FEMORAL FRACTURES; FEMUR; MORTALITY; REPLACEMENT; MORBIDITY AB Objective. To assess the association of specific comorbidities with periprosthetic fractures after primary total knee replacement (TKR). Methods. We used the prospectively collected data in the Mayo Clinic total joint registry from 1989-2008 on all patients who had undergone primary TKR. The outcome of interest was postoperative periprosthetic fractures during followup. The main predictors of interest were comorbidities grouped from the validated Deyo-Charlson index. Multivariable-adjusted Cox regression analyses were adjusted for sex, age, body mass index (BMI), American Society of Anesthesiology (ASA) class, operative diagnosis, and implant fixation. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated. Results. We included 17,633 primary TKRs with a mean followup of 6.3 years. The mean age was 68 years, 55% were women, and the mean BMI was 31 kg/m(2). There were 188 postoperative periprosthetic fractures on postoperative day 1 or later; 162 fractures (86%) occurred on postoperative day 90 or later. In multivariable analyses that simultaneously adjusted for all comorbidities and other variables (age, sex, BMI, ASA, operative diagnosis, and cement status), the following 2 conditions were significantly associated with an increased hazard of postoperative periprosthetic fractures: peptic ulcer disease (HR 1.87, 95% CI 1.28-2.75; P = 0.0014) and chronic obstructive pulmonary disease (HR 1.62, 95% CI 1.10-2.40; P = 0.02). Conclusion. Peptic ulcer disease and chronic obstructive pulmonary disease are associated with a higher risk of periprosthetic fractures after primary TKR. This may be related to the disease or its treatments, which need further study. Identification of specific risk factors may allow for implementation of intervention strategies to reduce this risk. C1 [Singh, Jasvinder A.] Univ Alabama, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Coll Med, Rochester, MN 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 singh, jasvinder/0000-0003-3485-0006 FU NIH [1-KL2-RR024151-01]; Abbott; Novartis; Savient; Takeda; URL Pharmaceuticals; Amgen; Wyeth; Zimmer; DePuy; Stryker; Osteotech FX Supported by an NIH Clinical Translational Science Award (grant 1-KL2-RR024151-01, Mayo Clinic Center for Clinical and Translational Research).; Dr. Singh has received consultant fees and/or honoraria (less than $10,000 each) from Abbott, Novartis, Savient, Takeda, and URL Pharmaceuticals, and has received research and travel grants from Amgen, Savient, Takeda, and Wyeth. Dr. Lewallen has received consultant fees and/or speaking fees (less than $10,000) from Zimmer; has received institutional research funds from DePuy, Stryker, and Zimmer; and has received royalties from Osteotech and Zimmer. NR 29 TC 6 Z9 7 U1 0 U2 2 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 OCT PY 2011 VL 63 IS 10 BP 1471 EP 1476 DI 10.1002/acr.20548 PG 6 WC Rheumatology SC Rheumatology GA 825FA UT WOS:000295255200015 PM 21748860 ER PT J AU Attridge, RT Frei, CR Restrepo, MI Lawson, KA Ryan, L Pugh, MJV Anzueto, A Mortensen, EM AF Attridge, R. T. Frei, C. R. Restrepo, M. I. Lawson, K. A. Ryan, L. Pugh, M. J. V. Anzueto, A. Mortensen, E. M. TI Guideline-concordant therapy and outcomes in healthcare-associated pneumonia SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE Drug resistance; guidelines for management of pneumonia; health outcomes; pneumonia ID COMMUNITY-ACQUIRED PNEUMONIA; SINGLE-CENTER EXPERIENCE; HOSPITALIZED-PATIENTS; ADMINISTRATIVE DATA; RESISTANT BACTERIA; UNITED-STATES; EPIDEMIOLOGY; MORTALITY; VALIDATION; PREDICTION AB Healthcare-associated pneumonia (HCAP) guidelines were first proposed in 2005 but have not yet been validated. The objective of this study was to compare 30-day mortality in HCAP patients treated with either guideline-concordant (GC)-HCAP therapy or GC community-acquired pneumonia (CAP) therapy. We performed a population-based cohort study of >150 hospitals in the US Veterans Health Administration. Patients were included if they had one or more HCAP risk factors and received antibiotic therapy within 48 h of admission. Critically ill patients were excluded. Independent risk factors for 30-day mortality were determined in a generalised linear mixed-effect model, with admitting hospital as a random effect. Propensity scores for the probability of receiving GC-HCAP therapy were calculated and incorporated into a second logistic regression model. A total of 15,071 patients met study criteria and received GC-HCAP therapy (8.0%), GC-CAP therapy (75.7%) or non-GC therapy (16.3%). The strongest predictors of 30-day mortality were recent hospital admission (OR 2.49, 95% CI 2.12-2.94) and GC-HCAP therapy (OR 2.18, 95% CI 1.86-2.55). GC-HCAP therapy remained an independent risk factor for 30-day mortality (OR 2.12, 95% CI 1.82-2.48) in the propensity score analysis. In nonsevere HCAP patients, GC-HCAP therapy is not associated with improved survival compared with GC-CAP therapy. C1 [Attridge, R. T.; Frei, C. R.; Ryan, L.] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, Sch Med, San Antonio, TX 78229 USA. [Attridge, R. T.] Univ Incarnate Word, Feik Sch Pharm, San Antonio, TX USA. [Restrepo, M. I.; Pugh, M. J. V.; Anzueto, A.; Mortensen, E. M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Restrepo, M. I.; Mortensen, E. M.] S Texas Vet Hlth Care Syst, VERDICT Res Program, San Antonio, TX USA. [Restrepo, M. I.; Pugh, M. J. V.; Anzueto, A.; Mortensen, E. M.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Attridge, R. T.; Frei, C. R.; Lawson, K. A.; Ryan, L.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. RP Frei, CR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, Sch Med, 7703 Floyd Curl Dr,MC 6220, San Antonio, TX 78229 USA. EM freic@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 OI Mortensen, Eric/0000-0002-3880-5563 FU National Institute of Nursing Research (Bethesda, MD, USA) [R01NR010828]; South Texas Veterans Health Care System (San Antonio, TX, USA); The University of Texas at Austin; National Institutes of Health [KL2 RR025766, K23HL096054]; The University of Texas at Austin College of Pharmacy; Ortho-McNeil Janssen (Titusville, NJ, USA); South Texas Veterans Health Care System Audie L. Murphy Division; The University of Texas Health Science Center at San Antonio FX This project was supported by a grant from the National Institute of Nursing Research (Bethesda, MD, USA; grant R01NR010828). 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 (San Antonio, TX, USA) and The University of Texas at Austin. E. M. Mortensen, the principal investigator, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. C. R. Frei is supported by a National Institutes of Health Grant KL2 RR025766, salary support from The University of Texas at Austin College of Pharmacy, and research support from Ortho-McNeil Janssen (Titusville, NJ, USA). M. I. Restrepo is supported by a National Institutes of Health Grant K23HL096054, salary support by the South Texas Veterans Health Care System Audie L. Murphy Division and The University of Texas Health Science Center at San Antonio. The funding agencies had no role in conducting the study, or role in the preparation, review or approval of the manuscript. The views expressed in this article are those of the authors and do not necessarily represent the views of the Dept of Veterans Affairs (Washington, DC, USA). NR 29 TC 54 Z9 55 U1 0 U2 2 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD OCT PY 2011 VL 38 IS 4 BP 878 EP 887 DI 10.1183/09031936.00141110 PG 10 WC Respiratory System SC Respiratory System GA 827EK UT WOS:000295410200019 PM 21436359 ER PT J AU Wang, FM Galson, DL Roodman, GD Ouyang, HJ AF Wang, Feng-Ming Galson, Deborah L. Roodman, G. David Ouyang, Hongjiao TI Resveratrol triggers the pro-apoptotic endoplasmic reticulum stress response and represses pro-survival XBP1 signaling in human multiple myeloma cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID UNFOLDED PROTEIN RESPONSE; FACTOR-KAPPA-B; TRANSCRIPTION FACTOR; MESSENGER-RNA; ER STRESS; DIFFERENTIATION; ACTIVATION; IRE1; PROLIFERATION; PATHOGENESIS AB Objective. Resveratrol, trans-3, 4', 5,-trihydroxystilbene, suppresses multiple myeloma (MM). The endoplasmic reticulum (ER) stress response component inositol-requiring enzyme 1 alpha (IRE1 alpha)/X-box binding protein 1 (XBP1) axis is essential for MM pathogenesis. We investigated the molecular action of resveratrol on IRE1 alpha/XBP1 axis in human MM cells. Materials and Methods. Human MM cell lines ANBL-6, OPM2, and MM.1S were utilized to determine the molecular signaling events following treatment with resveratrol. The stimulation of IRE1 alpha/XBP1 axis was analyzed by Western blot and reverse transcription polymerase chain reaction. The effect of resveratrol on the transcriptional activity of spliced XBP1 was assessed by luciferase assays. Chromatin immunoprecipitation was performed to determine the effects of resveratrol on the DNA binding activity of XBP1 in MM cells. Results. Resveratrol activated IRE1 alpha as evidenced by XBP1 messenger RNA splicing and phosphorylation of both IRE1 alpha and its downstream kinase c-Jun N-terminal kinase in MM cells. These responses were associated with resveratrol-induced cytotoxicity of MM cells. Resveratrol selectively suppressed the transcriptional activity of XBP1s while it stimulated gene expression of the molecules that are regulated by the non-IRE1/XBP1 axis of the ER stress response. Luciferase assays indicated that resveratrol suppressed the transcriptional activity of XBP1s through sirtuin 1, a downstream molecular target of resveratrol. Chromatin immunoprecipitation studies revealed that resveratrol decreased the DNA binding capacity of XBP1 and increased the enrichment of sirtuin 1 at the XBP1 binding region in the XBP1 promoter. Conclusions. Resveratrol exerts its chemotherapeutic effect on human MM cells through mechanisms involving the impairment of the pro-survival XBP1 signaling and the activation of pro-apoptotic ER stress response. (C) 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 [Galson, Deborah L.; Roodman, G. David; Ouyang, Hongjiao] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Wang, Feng-Ming; Galson, Deborah L.; Roodman, G. David; Ouyang, Hongjiao] Univ Pittsburgh, Sch Med, Ctr Bone Biol UPMC, Pittsburgh, PA USA. [Wang, Feng-Ming] Sichuan Univ, State Key Lab Oral Dis, Chengdu 610064, Peoples R China. [Wang, Feng-Ming; Galson, Deborah L.; Roodman, G. David; Ouyang, Hongjiao] Univ Pittsburgh, Sch Med, Dept Med Hematol Oncol, Pittsburgh, PA USA. [Ouyang, Hongjiao] Univ Pittsburgh, Sch Dent Med, Dept Comprehens Care Restorat Dent & Endodont, Pittsburgh, PA USA. RP Ouyang, HJ (reprint author), VA Pittsburgh Healthcare Syst, R&D151-U,2W 143,Univ Dr C, Pittsburgh, PA 15240 USA. EM hoo1@pitt.edu RI Wang, Fengming/H-6450-2011; Galson, Deborah/E-9370-2010 OI Wang, Fengming/0000-0001-5340-228X; Galson, Deborah/0000-0002-2045-8807 FU National Institutes of Health, Bethesda, MD, USA [DE017439]; Multiple Myeloma Research Foundation; VA Merit Review Fund; National Natural Science Foundation, P. R. China [30901677] FX This work was supported by grants from the National Institutes of Health, Bethesda, MD, USA (grant number DE017439 to H.-J.O.), the Multiple Myeloma Research Foundation (to H.-J.O.), and the VA Merit Review Fund (to G.D.R.). F.M.W is in part supported by the National Natural Science Foundation, P. R. China (grant number 30901677). We acknowledge the Veterans Administration Pittsburgh Healthcare System Research and Development for the use of their facilities. NR 33 TC 33 Z9 34 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD OCT PY 2011 VL 39 IS 10 BP 999 EP 1006 DI 10.1016/j.exphem.2011.06.007 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 827KL UT WOS:000295427300005 PM 21723843 ER PT J AU Carlson, KF Gravely, AA Noorbaloochi, S Simon, AB Bangerter, AK Sayer, NA AF Carlson, Kathleen F. Gravely, Amy A. Noorbaloochi, Siamak Simon, Alisha Baines Bangerter, Ann K. Sayer, Nina A. TI Post-deployment injury among new combat veterans enrolled in Veterans Affairs (VA) healthcare SO INJURY PREVENTION LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MORTALITY; IRAQ AB The purpose of this study was to examine prevalence and potential risk factors for post-deployment injury among Iraq and Afghanistan combat veterans enrolled in Veterans Affairs (VA) healthcare. A national, stratified sample of Iraq/Afghanistan combat Veteran VA users was surveyed in 2008. Mental and physical health, including medically-treated injuries sustained since deployment, were self-reported. Injury risk was estimated using survey logistic regression. Stratified ORs and 95% CIs were adjusted for potential confounders and non-response bias and weighted to represent the target population. Nearly half the population reported post-deployment injuries. In multivariate models, veterans with probable post-traumatic stress disorder (OR=2.1; 95% CI 1.3 to 3.5), self-reported diagnosed depression (OR=3.6; 95% CI 1.8 to 7.0) and anger problems (OR=2.4; 95% CI 1.4 to 4.2) had greater odds of post-deployment injury. Deployment-related injuries were also strongly associated with odds of post-deployment injury. Results suggest that mental health disorders increase the odds of post-deployment injury among combat veteran VA users. Longitudinal research examining these associations is warranted. C1 [Carlson, Kathleen F.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, Portland, OR USA. [Carlson, Kathleen F.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Gravely, Amy A.; Noorbaloochi, Siamak; Simon, Alisha Baines; Bangerter, Ann K.; Sayer, Nina A.] Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Noorbaloochi, Siamak; Sayer, Nina A.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. [Sayer, Nina A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. RP Carlson, KF (reprint author), Portland VA Med Ctr R&D 66, Portland Ctr Study Chron Comorbid Mental & Phys D, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM kathleen.carlson@va.gov RI Schueter, nicos/A-3625-2014; Sayer, Nina/E-3249-2016 FU US Department of Veterans Affairs (VA), Veterans Health Administration, Health Services Research and Development Service [RRP 07-315, TPP 67-005, CDA 08-025] FX This research was supported by the US Department of Veterans Affairs (VA), Veterans Health Administration, Health Services Research and Development Service grants (RRP 07-315; TPP 67-005; CDA 08-025). The findings and conclusions of this manuscript are those of the authors and do not necessarily represent those of the VA. NR 20 TC 4 Z9 4 U1 1 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1353-8047 J9 INJURY PREV JI Inj. Prev. PD OCT PY 2011 VL 17 IS 5 BP 343 EP 347 DI 10.1136/ip.2010.030213 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 823MB UT WOS:000295125300012 PM 21546526 ER PT J AU Clines, GA Mohammad, KS Grunda, JM Clines, KL Niewolna, M McKenna, CR McKibbin, CR Yanagisawa, M Suva, LJ Chirgwin, JM Guise, TA AF Clines, Gregory A. Mohammad, Khalid S. Grunda, Jessica M. Clines, Katrina L. Niewolna, Maria McKenna, C. Ryan McKibbin, Christopher R. Yanagisawa, Masashi Suva, Larry J. Chirgwin, John M. Guise, Theresa A. TI Regulation of Postnatal Trabecular Bone Formation by the Osteoblast Endothelin A Receptor SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE ENDOTHELIN A RECEPTOR; ENDOTHELIN-1; OSTEOBLAST; BONE; SEX STEROIDS ID ANDROGEN DEPRIVATION THERAPY; PULMONARY ARTERIAL-HYPERTENSION; RECOMBINANT CONGENIC MICE; SITE-SPECIFIC REGULATION; QUANTITATIVE TRAIT LOCI; PROSTATE-CANCER; OSTEOCLAST FORMATION; GROWTH; PATHWAY; CELLS AB Endothelin-1 (ET-1) is a potent vasoconstrictor that also stimulates cells in the osteoblast lineage by binding to the endothelin A receptor (ETAR). ET-1 ligand is widely secreted, particularly by the vasculature. However, the contributions of ETAR signaling to adult bone homeostasis have not been defined. ETAR was inactivated in osteoblasts by crossing ETAR-floxed and osteocalcin-Cre mice. Histomorphometric analyses were performed on 4-, 8-, and 12-week-old osteoblast-targeted ETAR knockout (KO) and wild-type (WT) male and female mice. Tibial trabecular bone volume was significantly lower from 12 weeks in KO versus WT mice in both males and females. Bone-formation rate, osteoblast density, and in vitro osteoblast differentiation were reduced by targeted inactivation of ETAR. A separate longitudinal analysis was performed between 8 and 64 weeks to examine the effect of aging and castration on bone metabolism in ETAR KO mice. Hypogonadism did not change the rate of bone accrual in WT or KO females. However, eugonadal KO males had a significantly larger increase in tibial and femoral bone acquisition than WT mice. Male mice castrated at: 8 weeks of age showed the reverse: KO mice had reduced rates of tibial and femoral BMD acquisition compared with WT mice. In vitro, ET-1 increased osteoblast proliferation, survival, and differentiation. Dihydrotestosterone also increased osteoblast differentiation using a mechanism distinct from the actions of ET-1. These results demonstrate that endothelin signaling in osteoblasts is an important regulator of postnatal trabecular bone remodeling and a modulator of androgen effects on bone. (C) 2011 American Society for Bone and Mineral Research. C1 [Clines, Gregory A.] Univ Alabama, Dept Med, Birmingham VA Med Ctr, Div Endocrinol Diabet & Metab,Endocrinol Sect, Birmingham, AL 35294 USA. [Clines, Gregory A.] Vet Affairs Med Ctr, Birmingham, AL USA. [Clines, Gregory A.; Mohammad, Khalid S.; Clines, Katrina L.; Niewolna, Maria; McKenna, C. Ryan; McKibbin, Christopher R.; Chirgwin, John M.; Guise, Theresa A.] Univ Virginia, Dept Med, Div Endocrinol & Metab, Charlottesville, VA USA. [Yanagisawa, Masashi] Univ Texas SW Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA. [Yanagisawa, Masashi] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. [Suva, Larry J.] Univ Arkansas Med Sci, Ctr Orthopaed Res, Dept Orthopaed Surg, Little Rock, AR 72205 USA. RP Clines, GA (reprint author), Univ Alabama, Dept Med, Birmingham VA Med Ctr, Div Endocrinol Diabet & Metab,Endocrinol Sect, 1808 7th Ave S,BDB 730, Birmingham, AL 35294 USA. EM clines@uab.edu FU NIH [R01 DK067333, F32 AR52295, K08 118428]; Gerald D Aurbach Endowment; Carl L Nelson Chair in Orthopaedic Creativity; Mellon Institute and Cancer Center of the University of Virginia; Endocrine Fellows Foundation FX This work was supported by NIH Grants R01 DK067333, F32 AR52295, and K08 118428; the Gerald D Aurbach Endowment, the Carl L Nelson Chair in Orthopaedic Creativity; the Mellon Institute and Cancer Center of the University of Virginia; and the Endocrine Fellows Foundation. We would like to thank Dr Thomas Clemens for providing osteocalcin-Cre mice and helpful discussions, the UAB Center for Metabolic Bone Disease Bone Histomorphometry Core, and the UAB Center for AIDS Research Flow Cytometry Core. NR 47 TC 12 Z9 12 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2011 VL 26 IS 10 BP 2523 EP 2536 DI 10.1002/jbmr.450 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 824ZQ UT WOS:000295241100019 PM 21698666 ER PT J AU Bhatt, AB Brenner, RP Van Cott, AC AF Bhatt, Amar B. Brenner, Richard P. Van Cott, Anne C. TI Generalized Paroxysmal Fast Activity and Tonic Seizures in Older Adults SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Tonic movements; Generalized epilepsy; Adult epilepsy; Lennox-Gastaut syndrome ID ABSENCE SEIZURES AB Generalized paroxysmal fast activity is an uncommon ictal EEG pattern usually associated with tonic seizures. Patients with generalized paroxysmal fast activity typically have multiple seizure types beginning in childhood and are refractory to antiepileptic drug therapy. We describe 3 hospitalized adult patients (age, older than 55 years) with new-onset tonic movements, noted during an acute illness, associated with generalized paroxysmal fast activity on EEG. These seizures were characterized by subtle stiffening of the arms, trunk, and face for up to 3 seconds. All patients had multiple medical problems and polypharmacy. None had a history of static encephalopathy, other epileptiform abnormalities on EEG, other seizure types, or significant neuroimaging abnormalities. In contrast to previously described reports in children, all three adults responded to antiepileptic drug monotherapy. EEG played a critical role in differentiating tonic seizures from nonepileptic movements in these three cases. C1 [Bhatt, Amar B.; Brenner, Richard P.; Van Cott, Anne C.] Univ Pittsburgh, Dept Neurol, Med Ctr, Pittsburgh, PA 15260 USA. [Van Cott, Anne C.] Vet Affairs Pittsburgh Hlth Care Syst, Div Neurol, Pittsburgh, PA USA. RP Bhatt, AB (reprint author), Vanderbilt Univ, Med Ctr, Dept Neurol, 1161 21st Ave S,A-0118 Med Ctr N, Nashville, TN 37232 USA. EM biga898@gmail.com NR 11 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD OCT PY 2011 VL 28 IS 5 BP 474 EP 477 DI 10.1097/WNP.0b013e318231c8dd PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 827DZ UT WOS:000295409100006 PM 21946373 ER PT J AU Axon, RN Tice, JA Egede, LE AF Axon, R. Neal Tice, Jeffrey A. Egede, Leonard E. TI Vitamin D as a Mediator of Racial Differences in Blood Pressure SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID UNITED-STATES; HYPERTENSION; HEALTH; TRENDS; RISK; SUPPLEMENTATION; PREVALENCE; AWARENESS; DISEASE; ADULTS C1 [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Axon, R. Neal; Egede, Leonard E.] Ralph H Johnson VAMC, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Axon, R. Neal; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Dept Med, Charleston, SC 29425 USA. [Tice, Jeffrey A.] Univ Calif San Francisco, Div Gen Internal Med, Dept Med, San Francisco, CA 94143 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU NIDDK NIH HHS [K24 DK093699] NR 17 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2011 VL 26 IS 10 BP 1088 EP 1089 DI 10.1007/s11606-011-1791-9 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600004 PM 21748433 ER PT J AU Lyles, CR Karter, AJ Young, BA Spigner, C Grembowski, D Schillinger, D Adler, N AF Lyles, Courtney R. Karter, Andrew J. Young, Bessie A. Spigner, Clarence Grembowski, David Schillinger, Dean Adler, Nancy TI Patient-Reported Racial/Ethnic Healthcare Provider Discrimination and Medication Intensification in the Diabetes Study of Northern California (DISTANCE) SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE diabetes; healthcare disparities; managed care; race/ethnicity; quality; discrimination ID QUALITY-OF-CARE; PERCEIVED DISCRIMINATION; HYPERTENSION MANAGEMENT; RACIAL-DISCRIMINATION; TECHNICAL QUALITY; CLINICAL-PRACTICE; BLOOD-PRESSURE; UNITED-STATES; ADHERENCE; DISEASE AB BACKGROUND: Racial/ethnic minority patients are more likely to report experiences with discrimination in the healthcare setting, potentially leading to reduced access to appropriate care; however, few studies evaluate reports of discrimination with objectively measured quality of care indicators. OBJECTIVE: To evaluate whether patient-reported racial/ethnic discrimination by healthcare providers was associated with evidence of poorer quality care measured by medication intensification. RESEARCH DESIGN AND PARTICIPANTS: Baseline data from the Diabetes Study of Northern California (DISTANCE), a random, race-stratified sample from the Kaiser Permanente Diabetes Registry from 2005-2006, including both survey and medical record data. MAIN MEASURES: Self-reported healthcare provider discrimination (from survey data) and medication intensification (from electronic prescription records) for poorly controlled diabetes patients (A1c >= 9.0%; systolic BP >= 140 mmHg or diastolic BP >= 90 mmHg; low-density lipoprotein (LDL) >= 130 mg/dl). KEY RESULTS: Of 10,409 eligible patients, 21% had hyperglycemia, 14% had hyperlipidemia, and 32% had hypertension. Of those with hyperglycemia, 59% had their medications intensified, along with 40% with hyperlipidemia, 33% with hypertension, and 47% in poor control of any risk factor. In adjusted log-binomial GEE models, discrimination was not associated with medication intensification [RR = 0.96 (95% CI: 0.74, 1.24) for hyperglycemia, RR = 1.23 (95% CI: 0.93, 1.63) for hyperlipidemia, RR = 1.06 (95% CI: 0.69, 1.61) for hypertension, and RR = 1.08 (95% CI: 0.88, 1.33) for the composite cohort]. CONCLUSIONS: We found no evidence that patient-reported healthcare discrimination was associated with less medication intensification. While not associated with this technical aspect of care, discrimination could still be associated with other aspects of care (e.g., patient-centeredness, communication). C1 [Lyles, Courtney R.; Spigner, Clarence; Grembowski, David] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Karter, Andrew J.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Young, Bessie A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Adler, Nancy] UCSF, Ctr Hlth & Community, San Francisco, CA USA. [Schillinger, Dean] UCSF, San Francisco Gen Hosp, Ctr Vulnerable Populat, San Francisco, CA USA. RP Lyles, CR (reprint author), Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Box 359455, Seattle, WA 98195 USA. EM crees@u.washington.edu FU National Research Service; AHRQ [HS013853]; NIDDK [R01 DK65664, R01 DK080726]; NICHD [R01 HD46113] FX This project was supported by a National Research Service Award, grant number HS013853 from AHRQ, and funds were provided by NIDDK R01 DK65664, NICHD R01 HD46113, and NIDDK R01 DK080726. None of the authors had conflicts of interest, and the funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. All authors contributed to the conception and design, and drafting and critical revision of the manuscript, including final approval of the version to be published. NR 43 TC 5 Z9 5 U1 2 U2 7 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 OCT PY 2011 VL 26 IS 10 BP 1138 EP 1144 DI 10.1007/s11606-011-1729-2 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600014 PM 21547610 ER PT J AU Ahluwalia, SC Gross, CP Chaudhry, SI Leo-Summers, L Van Ness, PH Fried, TR AF Ahluwalia, Sangeeta C. Gross, Cary P. Chaudhry, Sarwat I. Leo-Summers, Linda Van Ness, Peter H. Fried, Terri R. TI Change in Comorbidity Prevalence with Advancing Age Among Persons with Heart Failure SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE heart failure; comorbidity; prevalence; age groups ID OBSTRUCTIVE PULMONARY-DISEASE; MULTIPLE CHRONIC CONDITIONS; CHRONIC KIDNEY-DISEASE; ELDERLY POPULATION; DIASTOLIC FUNCTION; OLDER PATIENTS; IMPACT; MORTALITY; ENALAPRIL; SURVIVAL AB BACKGROUND: Comorbidity-a condition that co-exists with a primary illness-is common among older persons with heart failure and can complicate the overall management of this population. OBJECTIVES: To determine the relationship between advancing age and the prevalence and patterns of comorbidity among older persons with heart failure. DESIGN: Retrospective longitudinal cohort study PARTICIPANTS: A total of 201,130 Medicare beneficiaries with heart failure stratified into three age strata in 2001: 66-75, 76-85, and 86+ years, and followed over 5 years. MEASUREMENTS: (1) Prevalence of 19 conditions as identified by the Chronic Conditions Warehouse from Medicare claims data, characterized as concordant (related to heart failure) or discordant (unrelated to heart failure), and (2) overall comorbidity burden, defined as count of conditions. RESULTS: The median number of comorbidities rose from four (IQR: 2-5) to five (IQR: 4-7) among the young-old, and from 4 (IQR: 3-6) to 6 (IQR: 5-8) among the middle-old and oldest-old between 2001 and 2006. In 2001, the majority of concordant conditions were more prevalent among the youngest than oldest beneficiaries (e.g., diabetes 46.2% vs 26.9%; kidney disease 21.8% vs 18.4%), while the majority of discordant conditions were more prevalent among the oldest-old than youngest-old beneficiaries (e.g., dementia 39.6% vs 9.9%; hip fracture 9.5% vs 1.9%). Discordant conditions increased in prevalence faster among the oldest than youngest beneficiaries (e.g., dementia 13% points versus 9% points). CONCLUSION: Among older Medicare beneficiaries with heart failure, there is a higher overall burden of comorbidity and greater prevalence of discordant comorbidity among the oldest old. Comorbidity prevalence increases over time, with discordant comorbidity increasing at the fastest rate among the oldest old. This comorbidity burden highlights the challenge of effectively treating heart failure while simultaneously managing co-existing and unrelated conditions. C1 [Ahluwalia, Sangeeta C.] VA Greater Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Los Angeles, CA 90064 USA. [Gross, Cary P.; Chaudhry, Sarwat I.] Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, New Haven, CT 06510 USA. [Leo-Summers, Linda; Van Ness, Peter H.] Yale Univ, Sch Med, Program Aging, New Haven, CT 06510 USA. [Van Ness, Peter H.; Fried, Terri R.] Yale Univ, Sch Med, Dept Internal Med, Sect Geriatr, New Haven, CT 06510 USA. [Fried, Terri R.] VA Connecticut Healthcare Syst, Clin Epidemiol Res Ctr, West Haven, CT USA. RP Ahluwalia, SC (reprint author), VA Greater Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, 11301 Wilshire Blvd 111-G, Los Angeles, CA 90064 USA. EM sangeeta.ahluwalia@va.gov FU National Institute on Aging [T32AG1934, K24 AG028443, K23AG030986]; Office of Academic Affiliation at the VA Greater Los Angeles HSR&D Center of Excellence; Claude D. Pepper Older Americans Independence Center at Yale University School of Medicine [2P30AG021342-06 NIH/NIA] FX Dr. Ahluwalia was supported by a training grant from the National Institute on Aging (T32AG1934) and is currently supported by an Office of Academic Affiliation's VA Associated Health Postdoctoral Fellowship Program at the VA Greater Los Angeles HSR&D Center of Excellence. Dr. Fried is a recipient of a Midcareer Investigator Award in Patient-Oriented Research from the National Institute on Aging (K24 AG028443). Dr. Chaudhry is the recipient of a Paul Beeson/K23 Career Development Award (K23AG030986) from the National Institute on Aging. Supported by the Claude D. Pepper Older Americans Independence Center at Yale University School of Medicine (#2P30AG021342-06 NIH/NIA). NR 41 TC 23 Z9 23 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2011 VL 26 IS 10 BP 1145 EP 1151 DI 10.1007/s11606-011-1725-6 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600015 PM 21573881 ER PT J AU Steinman, MA Harlow, JB Massie, BM Kaboli, PJ Fung, KZ Heidenreich, PA AF Steinman, Michael A. Harlow, John B. Massie, Barry M. Kaboli, Peter J. Fung, Kathy Z. Heidenreich, Paul A. TI Age and Receipt of Guideline-Recommended Medications for Heart Failure: A Nationwide Study of Veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE guideline adherence; heart failure; aging; health services research; quality of care ID QUALITY-OF-CARE; BETA-BLOCKER THERAPY; CONVERTING ENZYME-INHIBITORS; OLDER PATIENTS; DIABETES-MELLITUS; CLINICAL-PRACTICE; MANAGED MEDICARE; ELDERLY-PATIENTS; NORTH-CAROLINA; TRIAL AB BACKGROUND: Older patients often receive less guideline-concordant care for heart failure than younger patients. OBJECTIVE: To determine whether age differences in heart failure care are explained by patient, provider, and health system characteristics and/or by chart-documented reasons for non-adherence to guidelines. DESIGN AND PATIENTS: Retrospective cohort study of 2,772 ambulatory veterans with heart failure and left ventricular ejection fraction < 40% from a 2004 nationwide medical record review program (the VA External Peer Review Program). MAIN MEASURES: Ambulatory use of ACE inhibitors, angiotensin receptor blockers (ARBs), and beta blockers. RESULTS: Among 2,772 patients, mean age was 73 +/- 10 years, 87% received an ACE inhibitor or ARB, and 82% received a beta blocker. When patients with explicit chart-documented reasons for not receiving these drugs were excluded, 95% received an ACE inhibitor or ARB and 89% received a beta blocker. In multivariable analyses controlling for a variety of patient and health system characteristics, the adjusted odds ratio for ACE-inhibitor and ARB use was 0.43 (95% CI 0.24-0.78) for patients age 80 and over vs. those age 50-64 years, and the adjusted odds ratio for beta blocker use was 0.66 (95% CI 0.48-0.93) between the two age groups. The magnitude of these associations was similar but not statistically significant after excluding patients with chart-documented reasons for not prescribing ACE inhibitors or ARBs and beta blockers. CONCLUSIONS: A high proportion of veterans receive guideline-recommended medications for heart failure. Older veterans are consistently less likely to receive these drugs, although these differences were no longer significant when accounting for patients with chart-documented reasons for not prescribing these drugs. Closely evaluating reasons for non-prescribing in older adults is essential to assessing whether non-treatment represents good clinical judgment or missed opportunities to improve care. C1 [Steinman, Michael A.] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program REAP, San Francisco, CA 94121 USA. [Steinman, Michael A.; Harlow, John B.; Fung, Kathy Z.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Steinman, Michael A.; Harlow, John B.; Massie, Barry M.; Fung, Kathy Z.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.] San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA USA. [Massie, Barry M.; Heidenreich, Paul A.] Vet Hlth Adm Congest Heart Failure Qual Enhanceme, Washington, DC USA. [Kaboli, Peter J.] Iowa City VA Healthcare Syst, Comprehens Access & Delivery Res & Evaluat CADR, Iowa City, IA USA. [Kaboli, Peter J.] Univ Iowa, Carver Coll Med, Dept Internal Med, Div Gen Internal Med, Iowa City, IA USA. [Heidenreich, Paul A.] Palo Alto VA Hlth Care Syst, Div Cardiol, Palo Alto, CA USA. [Heidenreich, Paul A.] Stanford Univ, Palo Alto, CA 94304 USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program REAP, 4150 Clement St,VA Box 181 G, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu OI Heidenreich, Paul/0000-0001-7730-8490 FU VA Health Services Research and Development Service [IIR 06-080-2]; National Institute on Aging; American Federation for Aging Research [K23-AG030999] FX This work was funded by the VA Health Services Research and Development Service (IIR 06-080-2, Dr. Steinman) and by the National Institute on Aging and American Federation for Aging Research (K23-AG030999, Dr. Steinman). The funding sources had no control over the analysis, writing, or decision to publish this manuscript. NR 44 TC 4 Z9 4 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 OCT PY 2011 VL 26 IS 10 BP 1152 EP 1159 DI 10.1007/s11606-011-1745-2 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600016 PM 21604076 ER PT J AU Seal, KH Cohen, G Bertenthal, D Cohen, BE Maguen, S Daley, A AF Seal, Karen H. Cohen, Greg Bertenthal, Daniel Cohen, Beth E. Maguen, Shira Daley, Aaron TI Reducing Barriers to Mental Health and Social Services for Iraq and Afghanistan Veterans: Outcomes of an Integrated Primary Care Clinic SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE veterans; mental health; health services utilization; primary care ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; COLLABORATIVE CARE; WAR VETERANS; RISK-FACTORS; US-VETERANS; DEPRESSION; DIAGNOSES; COMBAT; ASSOCIATION AB BACKGROUND: Despite high rates of post-deployment psychosocial problems in Iraq and Afghanistan veterans, mental health and social services are under-utilized. OBJECTIVE: To evaluate whether a Department of Veterans Affairs (VA) integrated care (IC) clinic (established in April 2007), offering an initial three-part primary care, mental health and social services visit, improved psychosocial services utilization in Iraq and Afghanistan veterans compared to usual care (UC), a standard primary care visit with referral for psychosocial services as needed. DESIGN: Retrospective cohort study using VA administrative data. POPULATION: Five hundred and twenty-six Iraq and Afghanistan veterans initiating primary care at a VA medical center between April 1, 2005 and April 31, 2009. MAIN MEASURES: Multivariable models compared the independent effects of primary care clinic type (IC versus UC) on mental health and social services utilization outcomes. KEY RESULTS: After 2007, compared to UC, veterans presenting to the IC primary care clinic were significantly more likely to have had a within-30-day mental health evaluation (92% versus 59%, p < 0.001) and social services evaluation [77% (IC) versus 56% (UC), p < 0.001]. This exceeded background system-wide increases in mental health services utilization that occurred in the UC Clinic after 2007 compared to before 2007. In particular, female veterans, younger veterans, and those with positive mental health screens were independently more likely to have had mental health and social service evaluations if seen in the IC versus UC clinic. Among veterans who screened positive for a parts per thousand yenaEuro parts per thousand 1 mental health disorder(s), there was a median of 1 follow-up specialty mental health visit within the first year in both clinics. CONCLUSIONS: Among Iraq and Afghanistan veterans new to primary care, an integrated primary care visit further improved the likelihood of an initial mental health and social services evaluation over background increases, but did not improve retention in specialty mental health services. C1 [Seal, Karen H.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Seal, Karen H.; Cohen, Greg; Bertenthal, Daniel; Cohen, Beth E.; Maguen, Shira; Daley, Aaron] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Seal, KH (reprint author), Univ Calif San Francisco, Dept Med, 4150 Clement St,Box 111A 1, San Francisco, CA 94121 USA. EM Karen.Seal@va.gov FU San Francisco VA HSR&D Research Enhancement Award Program; Department of Defense [W81XWH-08-2-0072, W81XWH-08-2-0106] FX We would like to thank Dr. Rina Shah and Dr. Dawn Lawhon for their leadership in the design and coordination of the SFVAMC Integrated Care Clinic. We acknowledge the support of the San Francisco VA HSR&D Research Enhancement Award Program. We would also like to thank Ms. Ann Chu for her assistance in data abstraction. Finally, we acknowledge and thank veterans of Iraq and Afghanistan for their service to our country.; This study was funded by Department of Defense awards W81XWH-08-2-0072 and W81XWH-08-2-0106. The funders had no role in the design, data analysis, writing or approval of the manuscript. NR 57 TC 20 Z9 20 U1 1 U2 9 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 OCT PY 2011 VL 26 IS 10 BP 1160 EP 1167 DI 10.1007/s11606-011-1746-1 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600017 PM 21647750 ER PT J AU Grenard, JL Munjas, BA Adams, JL Suttorp, M Maglione, M McGlynn, EA Gellad, WF AF Grenard, Jerry L. Munjas, Brett A. Adams, John L. Suttorp, Marika Maglione, Margaret McGlynn, Elizabeth A. Gellad, Walid F. TI Depression and Medication Adherence in the Treatment of Chronic Diseases in the United States: A Meta-Analysis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE depression; adherence; chronic disease; meta-analysis ID HYPERTENSIVE AFRICAN-AMERICANS; CORONARY-HEART-DISEASE; PATIENT-ADHERENCE; MATHEMATICAL CONTRIBUTIONS; MYOCARDIAL-INFARCTION; BLOOD-PRESSURE; META-ANALYSIS; NONADHERENCE; PREDICTORS; SYMPTOMS AB OBJECTIVE: To conduct a meta-analysis of the association between depression and medication adherence among patients with chronic diseases. Poor medication adherence may result in worse outcomes and higher costs than if patients fully adhere to their medication regimens. DATA SOURCES: We searched the PubMed and PsycINFO databases, conducted forward searches for articles that cited major review articles, and examined the reference lists of relevant articles. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: We included studies on adults in the United States that reported bivariate relationships between depression and medication adherence. We excluded studies on special populations (e.g., substance abusers) that were not representative of the general adult population with chronic diseases, studies on certain diseases (e.g., HIV) that required special adherence protocols, and studies on interventions for medication adherence. STUDY APPRAISAL AND SYNTHESIS METHODS: Data abstracted included the study population, the protocol, measures of depression and adherence, and the quantitative association between depression and medication adherence. Synthesis of the data followed established statistical procedures for meta-analysis. RESULTS: The estimated odds of a depressed patient being non-adherent are 1.76 times the odds of a non-depressed patient, across 31 studies and 18,245 participants. The association was similar across disease types but was not as strong among studies that used pharmacy records compared to self-report and electronic cap measures. LIMITATIONS: The meta-analysis results are correlations limiting causal inferences, and there is some heterogeneity among the studies in participant characteristics, diseases studied, and methods used. CONCLUSIONS: This analysis provides evidence that depression is associated with poor adherence to medication across a range of chronic diseases, and we find a new potential effect of adherence measurement type on this relationship. Although this study cannot assess causality, it supports the importance that must be placed on depression in studies that assess adherence and attempt to improve it. C1 [Grenard, Jerry L.] Claremont Grad Univ, Sch Community & Global Hlth, San Dimas, CA 91773 USA. [Munjas, Brett A.; Adams, John L.; Suttorp, Marika; Maglione, Margaret; Gellad, Walid F.] RAND Corp, Santa Monica, CA USA. [McGlynn, Elizabeth A.] Kaiser Permanente Ctr Effectiveness & Safety Res, Pasadena, CA USA. [Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gellad, Walid F.] Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Gellad, Walid F.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Grenard, JL (reprint author), Claremont Grad Univ, Sch Community & Global Hlth, 180 E Via Verde St,Suite 100, San Dimas, CA 91773 USA. EM jerry.grenard@cgu.edu FU Agency for Healthcare Research and Quality (AHRQ) [T32 HS00046-14]; VA HSR&D Career Development Award [CDA 09-207]; Mehlman Vogel Castagnetti FX This research was supported by the Agency for Healthcare Research and Quality (AHRQ: T32 HS00046-14), a VA HSR&D Career Development Award to Dr. Gellad (CDA 09-207), and by Mehlman Vogel Castagnetti. NR 88 TC 103 Z9 108 U1 6 U2 34 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 OCT PY 2011 VL 26 IS 10 BP 1175 EP 1182 DI 10.1007/s11606-011-1704-y PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600019 PM 21533823 ER PT J AU Erickson, B Dhaliwal, G Henderson, MC Amsterdam, E Rencic, J AF Erickson, Brandon Dhaliwal, Gurpreet Henderson, Mark C. Amsterdam, Ezra Rencic, Joseph TI Effusive Reasoning SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE pattern recognition; analytic reasoning; problem representation; clinical diagnostic reasoning ID PRIMARY SYSTEMIC AMYLOIDOSIS; RESTRICTIVE CARDIOMYOPATHY; CONSTRICTIVE PERICARDITIS; INVOLVEMENT; FEATURES C1 [Rencic, Joseph] Tufts Med Ctr, Dept Internal Med, Boston, MA 02111 USA. [Erickson, Brandon; Rencic, Joseph] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. [Henderson, Mark C.] Univ Calif Davis, Med Ctr, Dept Internal Med, Sacramento, CA 95817 USA. [Amsterdam, Ezra] Univ Calif Davis, Med Ctr, Div Cardiovasc Med, Dept Internal Med, Sacramento, CA 95817 USA. RP Rencic, J (reprint author), Tufts Med Ctr, Dept Internal Med, 750 Washington St,Box 398, Boston, MA 02111 USA. EM jrencic@tuftsmedicalcenter.org NR 15 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2011 VL 26 IS 10 BP 1204 EP 1208 DI 10.1007/s11606-011-1785-7 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600023 PM 21761239 ER PT J AU Erickson, B Dhaliwal, G Henderson, MC Amsterdam, E Rencic, J AF Erickson, Brandon Dhaliwal, Gurpreet Henderson, Mark C. Amsterdam, Ezra Rencic, Joseph TI Effusive Reasoning (vol 26, pg 1204, 2011) SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Correction C1 [Erickson, Brandon; Rencic, Joseph] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. [Amsterdam, Ezra] Calif State Univ Sacramento, Dept Internal Med, Davis Med Ctr, Div Cardiovasc Med, Sacramento, CA 95819 USA. [Rencic, Joseph] Tufts Med Ctr, Dept Internal Med, Boston, MA USA. RP Erickson, B (reprint author), Tufts Univ, Sch Med, Boston, MA 02111 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2011 VL 26 IS 10 BP 1235 EP 1235 DI 10.1007/s11606-011-1846-y PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600030 ER PT J AU Massie, BM AF Massie, Barry M. TI Novel targets for the treatment of heart failure: Perspectives from a heart failure clinician and trialist SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Editorial Material ID SURVIVAL; ENALAPRIL; MORTALITY C1 [Massie, Barry M.] Univ Calif San Francisco, Div Cardiol, San Francisco VAMC, San Francisco, CA 94143 USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Massie, BM (reprint author), Univ Calif San Francisco, Div Cardiol, San Francisco VAMC, San Francisco, CA 94143 USA. EM barry.massie@va.gov NR 8 TC 6 Z9 6 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD OCT PY 2011 VL 51 IS 4 BP 438 EP 440 DI 10.1016/j.yjmcc.2011.03.016 PG 3 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 825SR UT WOS:000295302900002 PM 21549124 ER PT J AU Mishra, RK Devereux, RB Cohen, BE Whooley, MA Schiller, NB AF Mishra, Rakesh K. Devereux, Richard B. Cohen, Beth E. Whooley, Mary A. Schiller, Nelson B. TI Prediction of Heart Failure and Adverse Cardiovascular Events in Outpatients with Coronary Artery Disease Using Mitral E/A Ratio in Conjunction with E-Wave Deceleration Time: The Heart and Soul Study SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Echocardiography; Diastolic function; Mitral deceleration time; Mitral E-to-A ratio; Heart failure; Adverse cardiovascular events ID VENTRICULAR DYSFUNCTION; MYOCARDIAL-INFARCTION; DIASTOLIC FUNCTION; VELOCITY; ECHOCARDIOGRAPHY; RECOMMENDATIONS; MORTALITY; PRESSURE; LIFE AB Background: Deceleration time (DT) of early mitral inflow (E) is a marker of diastolic left ventricular (LV) chamber stiffness that is routinely measured during the quantitation of LV diastolic function with Doppler echocardiography. Shortened DT after myocardial infarction predicts worse cardiovascular outcome. Recent studies have shown that indexing DT to peak E-wave velocity (pE) augments its prognostic power in a population with a high prevalence of coronary risk factors and in patients with hypertension during antihypertensive treatment. However, in ambulatory subjects with stable coronary artery disease (CAD), it is not known whether DT predicts cardiovascular events and whether DT/pE improves its prognostic power. Methods: The ability of DT and DT/pE to predict heart failure (HF) hospitalizations and other major adverse cardiovascular events (MACEs) was studied prospectively in 926 ambulatory patients with stable CAD enrolled in the Heart and Soul Study. Unadjusted and multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for HF and other MACEs. Results: During a mean of 6.3 +/- 2.0 years, there were 124 hospitalizations for HF and 198 other MACEs. Relative to participants with mitral E/A ratios in the normal range (0.75 < E/A < 1.5; n = 604), those with E/A ratios >= 1.5 (n = 107) had an increased risk for HF (HR, 2.54; 95% CI, 1.52-4.25, P < .001) but not for other MACEs (HR, 1.00; 95% CI, 0.60-1.68; P = 1.00), while those with E/A ratios <= 0.75 (n = 215) were not at increased risk for either outcome. Among patients with normal E/A ratios, lower DT/pE predicted HF (HR, 0.47; 95% CI, 0.23-0.97, P = .04 per point increase in ln{msec/[cm/sec]}), while DT alone did not. However, in this group with normal E/A ratios, neither DT/pE nor DT alone was predictive of other MACEs. In patients with E/A ratios <= 0.75 (n = 215) and those with E/A ratios >= 1.5 (n = 107), neither DT nor DT/pE predicted either end point. Conclusions: In ambulatory patients with stable CAD, restrictive filling (E/A ratio >= 1.5) is a powerful predictor of HF. Among those with normal mitral E/A ratios (0.75-1.5), only DT/pE predicts HF, while neither DT nor DT/pE predicts other MACEs. This suggests that mitral E/A ratio has significant prognostic value in patients with CAD, and in those with normal mitral E/A ratios, the normalization of DT to pE augments its prognostic power. (J Am Soc Echocardiogr 2011;24:1134-40.) C1 [Mishra, Rakesh K.; Cohen, Beth E.; Whooley, Mary A.] Vet Affairs Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Mishra, Rakesh K.; Cohen, Beth E.; Whooley, Mary A.; Schiller, Nelson B.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Devereux, Richard B.] Weill Cornell Med Coll, Greenberg Div Cardiol, Dept Med, New York, NY USA. RP Mishra, RK (reprint author), San Francisco VA Med Ctr, Div Cardiol 111C, 4150 Clement St, San Francisco, CA 94121 USA. EM rakesh.mishra@ucsf.edu NR 17 TC 7 Z9 7 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD OCT PY 2011 VL 24 IS 10 BP 1134 EP 1140 DI 10.1016/j.echo.2011.06.003 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 827WE UT WOS:000295459200010 PM 21764551 ER PT J AU Gera, J Lichtenstein, A AF Gera, Joseph Lichtenstein, Alan TI The mammalian target of rapamycin pathway as a therapeutic target in multiple myeloma SO LEUKEMIA & LYMPHOMA LA English DT Review DE Multiple myeloma; mTOR; rapalogs ID PHASE-II TRIAL; RENAL-CELL CARCINOMA; PROTEIN-KINASE; WALDENSTROM MACROGLOBULINEMIA; ENHANCED SENSITIVITY; SYNERGISTIC ACTIVITY; INHIBITOR RAPAMYCIN; MTOR INHIBITION; AKT ACTIVITY; TUMOR-CELLS AB The mammalian target of rapamycin (mTOR) is centrally located, linking proximal oncogenic cascades to critical downstream pathways that drive tumor growth. mTOR regulates such diverse functions as protein translation, proliferation, viability, autophagy, metabolism homeostasis, monitoring of energy reserves, and induction of angiogenesis. Given its fundamental role in tumorigenesis, it is not surprising that a huge effort is being made to develop mTOR inhibitors. The existence of feedback pathways that become activated subsequent to mTOR inhibition has complicated these efforts. However, the fact that mTOR exists in two separate complexes, TORC1 and TORC2, and rapalogs primarily inhibit only TORC1 and TORC2 is actually a key activator of AKT, has injected new energy into the quest to find inhibitors that can inhibit both complexes. In myeloma models, preclinical studies confirm the activity of rapalogs as well as newer TORC1/TORC2 inhibitors, and early phase clinical trials have begun. In addition, the recent finding of up-regulated myeloma cell expression of DEPTOR, an mTOR binding protein that restricts mTOR activity, suggests an additional future therapeutic target specific to the myeloma tumor model. C1 UCLA Sch Med, Greater Los Angeles VA Healthcare Ctr, Div Hematol Oncol, Los Angeles, CA USA. Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. RP Lichtenstein, A (reprint author), VA W LA Hosp, W111H,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM alan.lichtenstein@med.va.gov NR 67 TC 17 Z9 19 U1 0 U2 0 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 OCT PY 2011 VL 52 IS 10 BP 1857 EP 1866 DI 10.3109/10428194.2011.580478 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 824CA UT WOS:000295176800009 PM 21599581 ER PT J AU Dash, R Chung, JH Chan, T Yamada, M Barral, J Nishimura, D Yang, PC Simpson, PC AF Dash, Rajesh Chung, Jaehoon Chan, Trevor Yamada, Mayumi Barral, Joelle Nishimura, Dwight Yang, Phillip C. Simpson, Paul C. TI A Molecular MRI Probe to Detect Treatment of Cardiac Apoptosis In Vivo SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cardiac MRI; apoptosis; doxorubicin; annexin-V; SPIO; alpha-1-adrenergic agonist ID MESENCHYMAL STEM-CELLS; MAGNETIC-RESONANCE; ANNEXIN-V; 1.5 T; CARDIOMYOPATHY; NANOPARTICLES; SURVIVAL; MYOCYTES; AGENT; DEATH AB Cell death by apoptosis is critical in myocardial diseases, and noninvasive detection of early, reversible apoptosis might be useful clinically. Exogenous Annexin-V (ANX) protein binds membrane phosphatidylserine, which is externalized in early apoptosis. A molecular MRI probe was constructed with superparamagnetic iron oxide (SPIO) conjugated to recombinant human ANX (ANX-SPIO). Apoptosis was induced with doxorubicin, a cardiotoxic cancer drug, in culture in neonatal rat ventricular myocytes, cardiac fibroblasts, and mesenchymal stem cells, and in vivo in the mouse heart. ANX-SPIO was validated using T2*-weighted 3T MRI. ANX-SPIO produced T2* signal loss, reflecting iron content, that correlated highly with independent apoptosis markers; bound with high affinity to apoptotic myocytes by competition assay (Ki 69 nM); detected apoptosis in culture much earlier than did TUNEL stain; and revealed fibroblast resistance to apoptosis. With apoptosis in vivo, ANX-SPIO produced diffuse myocardial T2* signal loss that correlated with increased iron stain and caspase activity. Treatment with an alpha-1-adrenergic agonist in vivo reversed apoptosis and eliminated the ANX-SPIO MRI signal. It is concluded that cardiac MRI of ANX-SPIO detects early, nonischemic cardiac apoptosis in culture and in vivo, and can identify reversibly injured cardiac cells in diseased hearts, when treatment is still possible. Magn Reson Med 66:1152-1162, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Dash, Rajesh; Chan, Trevor; Simpson, Paul C.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA USA. [Dash, Rajesh; Chan, Trevor; Simpson, Paul C.] San Francisco VA Med Ctr, Res Serv, San Francisco, CA USA. [Dash, Rajesh; Simpson, Paul C.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Dash, Rajesh; Simpson, Paul C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Dash, Rajesh; Chung, Jaehoon; Chan, Trevor; Yamada, Mayumi; Yang, Phillip C.] Stanford Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Barral, Joelle; Nishimura, Dwight] Stanford Univ, Med Ctr, Dept Elect Engn, Stanford, CA 94305 USA. RP Simpson, PC (reprint author), VA Med Ctr, 111-C-8,4150 Clement St, San Francisco, CA 94121 USA. EM paul.simpson@ucsf.edu FU VA; NIH; American Heart Association, Western States Affiliate; Sarnoff Cardiovascular Research Foundation FX Grant sponsors: VA and NIH; American Heart Association, Western States Affiliate; Sarnoff Cardiovascular Research Foundation. NR 28 TC 28 Z9 31 U1 1 U2 8 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 OCT PY 2011 VL 66 IS 4 BP 1152 EP 1162 DI 10.1002/mrm.22876 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 826LV UT WOS:000295356500027 PM 21360750 ER PT J AU Yaffe, K Lindquist, K Schwartz, AV Vitartas, C Vittinghoff, E Satterfield, S Simonsick, EM Launer, L Rosano, C Cauley, JA Harris, T AF Yaffe, K. Lindquist, K. Schwartz, A. V. Vitartas, C. Vittinghoff, E. Satterfield, S. Simonsick, E. M. Launer, L. Rosano, C. Cauley, J. A. Harris, T. TI Advanced glycation end product level, diabetes, and accelerated cognitive aging SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; OXIDATIVE STRESS; PENTOSIDINE; ACCUMULATION; DEMENTIA; DECLINE; ELDERS; HEALTH; SERUM AB Objective: Several studies report that diabetes increases risk of cognitive impairment; some have hypothesized that advanced glycation end products (AGEs) underlie this association. AGEs are cross-linked products that result from reactions between glucose and proteins. Little is known about the association between peripheral AGE concentration and cognitive aging. Methods: We prospectively studied 920 elders without dementia, 495 with diabetes and 425 with normal glucose (mean age 74.0 years). Using mixed models, we examined baseline AGE concentration, measured with urine pentosidine and analyzed as tertile, and performance on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and repeatedly over 9 years. Incident cognitive impairment (a decline of > 1.0 SD on each test) was analyzed with logistic regression. Results: Older adults with high pentosidine level had worse baseline DSST score (p = 0.05) but not different 3MS score (p = 0.32). On both tests, there was a more pronounced 9-year decline in those with high and mid pentosidine level compared to those in the lowest tertile (3MS 7.0, 5.4, and 2.5 point decline, p overall < 0.001; DSST 5.9, 7.4, and 4.5 point decline, p = 0.03). Incident cognitive impairment was higher in those with high or mid pentosidine level than those in the lowest tertile (3MS: 24% vs 17%, odds ratio = 1.55; 95% confidence interval 1.07-2.26; DSST: 31% vs 22%, odds ratio = 1.62; 95% confidence interval 1.13-2.33). There was no interaction between pentosidine level, diabetes status, and cognitive decline. Multivariate adjustment for age, sex, race, education, hypertension, cardiovascular disease, estimated glomerular filtration rate, and diabetes diminished results somewhat but overall patterns remained similar. Conclusion: High peripheral AGE level is associated with greater cognitive decline in older adults with and without diabetes. Neurology (R) 2011;77:1351-1356 C1 [Yaffe, K.; Vitartas, C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, K.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, K.; Schwartz, A. V.; Vittinghoff, E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Lindquist, K.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Yaffe, K.; Vitartas, C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Satterfield, S.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Simonsick, E. M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Launer, L.; Harris, T.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Baltimore, MD 21224 USA. [Rosano, C.; Cauley, J. A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu OI Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010; Cauley, Jane A/0000-0003-0752-4408 FU NIH, National Institute of Aging; American Health Assistance Foundation [A201-0029]; Amgen; Merck Serono; GlaxoSmithKline; Anonymous Foundation; Alzheimer Association; NIH (NIA, NIDDK, NIMH); Department of Defense; NIH (NIDDK, NIA); Medtronic, Inc.; Zoll Medical Corporation; NIH (NIA, NIDDK, NHLBI, NIAID, NIMH); NIH/NIA; Novartis; NIH; NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] FX NIA contract nos. N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Aging, and by a grant from the American Health Assistance Foundation, grant no. A201-0029.; Dr. Yaffe has served on data safety monitoring boards for Pfizer Inc, Medivation, Inc. and the NIH (NIMH and NIA trials); and has received research support from the NIH (NIA, NIDDK, NIMH), the Department of Defense, American Health Assistance Foundation, Anonymous Foundation, and the Alzheimer Association. K. Lindquist reports no disclosures. Dr. Schwartz serves on a scientific advisory board for GlaxoSmithKline; has received speaker honoraria from Amgen and Merck Serono; has received funding for travel from Amgen; and receives research support from Merck Serono, GlaxoSmithKline, the NIH (NIDDK, NIA). C. Vitartas reports no disclosures. Dr. Vittinghoff receives publishing royalties for Regression Methods in Biostatistics: Linear, Logistic, Survival and Repeated Measures Models (Springer Verlag, 2005); and receives research support from Medtronic, Inc., Zoll Medical Corporation, Amgen, and the NIH (NIA, NIDDK, NHLBI, NIAID, NIMH). Dr. Satterfield receives research support from the NIH/NIA. Dr. Simonsick serves as an Associate Editor for the Journal of Gerontology Medical Sciences and on the editorial board of the Journal of Aging and Health. Dr. Launer receives research support from the NIH/NIA Intramural Research Program. Dr. Rosano reports no disclosures. Dr. Cauley receives research support from Novartis. Dr. Harris receives research support from the NIH. NR 31 TC 49 Z9 49 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 2011 VL 77 IS 14 BP 1351 EP 1356 DI 10.1212/WNL.0b013e3182315a56 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 828XV UT WOS:000295539000010 PM 21900628 ER PT J AU Oujiri, J Hakeem, A Pack, Q Holland, R Meyers, D Hildebrand, C Bridges, A Roach, MA Vogelman, B AF Oujiri, James Hakeem, Abdul Pack, Quinn Holland, Robert Meyers, David Hildebrand, Christopher Bridges, Alan Roach, Mary A. Vogelman, Bennett TI Republished original article: Resident-initiated interventions to improve inpatient heart-failure management SO POSTGRADUATE MEDICAL JOURNAL LA English DT Article ID ELECTRONIC HEALTH RECORD; ACUTE MYOCARDIAL-INFARCTION; CLINICAL DECISION-SUPPORT; QUALITY-OF-CARE; IMPLEMENTATION; PERFORMANCE; INDICATORS; MORTALITY; SYSTEMS; SAFETY AB Background: Third-year internal medicine residents participating in a quality improvement rotation identified gaps between the Joint Commission's ORYX quality guidelines and clinical practices for the inpatient management of heart failure (HF) at the William S. Middleton Memorial Veterans Hospital. Residents focused on the performance metrics associated with tobacco-cessation counselling documentation, ejection fraction assessment and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescriptions. Methods: After analysing data collected by the External Peer Review Program, residents reviewed the institution's admissions and discharge processes with the aim of improving quality and compliance. In redesigning these processes, residents created an admissions template and a discharge face sheet, and compared specific ORYX measure compliance rates before and after institution-wide implementation. Results: Following implementation of the tobacco-cessation admissions template, 100% of HF patients who used tobacco received documented cessation counselling, compared with 59% prior to intervention (p<0.01, n=32). Following implementation of the mandatory discharge face sheet, 97% of HF patients (compared with 92% preintervention, p>0.05) received comprehensive discharge instruction; LV function assessment went from 98% to 100% (p>0.05); and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription for left ventricular systolic dysfunction at discharge (or documentation of a contra-indication) went from 82% to 100% (p<0.01, n=48). Discussion: By implementing a standardised admissions template and a mandatory discharge face sheet, the hospital improved its processes of documentation and increased adherence to quality-performance measures. By strengthening residents' learning and commitment to quality improvement, the hospital created a foundation for future changes in the systems that affect patient care. C1 [Oujiri, James; Roach, Mary A.; Vogelman, Bennett] Univ Wisconsin Madison Sch Med & Publ Hlth, Madison, WI USA. [Oujiri, James; Holland, Robert; Meyers, David; Hildebrand, Christopher; Bridges, Alan] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Hakeem, Abdul] Univ Cincinnati Coll Med, Div Cardiovasc Dis, Cincinnati, OH USA. [Pack, Quinn] Henry Ford Hlth Syst K 14, Div Cardiovasc Dis, Detroit, MI USA. RP Vogelman, B (reprint author), Educ Program Off, Internal Med Residency Program, Suite 5000,1685 Highland Ave, Madison, WI 53705 USA. EM bsv@medicine.wisc.edu FU Medical Education and Research Committee (MERC) of the University of Wisconsin-Madison School of Medicine and Public Health; Residency Review Committee for Internal Medicine; William S Middleton Memorial Veterans Administration Hospital; University of Wisconsin Institute for Clinical and Translational Research; NIH [1 UL1RR025011] FX Completion of this paper was made possible by a grant from the Medical Education and Research Committee (MERC) of the University of Wisconsin-Madison School of Medicine and Public Health as well as by the support of the Education Innovation Project of the Residency Review Committee for Internal Medicine, of which we are a participating residency. These QI projects received widespread support from the William S Middleton Memorial Veterans Administration Hospital, especially the director, D Thompson, and personnel in the Information Technology, Pharmacy, Nursing, and Organisation Improvement departments. Results of these projects were shared at the Association of Program Directors in Internal Medicine (APDIM) meeting in April, 2009. We also wish to acknowledge the support of the University of Wisconsin Institute for Clinical and Translational Research, funded through an NIH Clinical and Translational Science Award (CTSA), grant no 1 UL1RR025011. NR 18 TC 0 Z9 0 U1 1 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0032-5473 J9 POSTGRAD MED J JI Postgrad. Med. J. PD OCT PY 2011 VL 87 IS 1032 BP 700 EP 705 DI 10.1136/pgmj.2009.39339rep PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 825GO UT WOS:000295259400009 PM 21954033 ER PT J AU Cersosimo, E Musi, N AF Cersosimo, Eugenio Musi, Nicolas TI Improving Treatment in Hispanic/Latino Patients SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Cultural competence; Hispanic; Latino; Treatment barriers; Type 2 diabetes mellitus ID DIABETES SELF-MANAGEMENT; LIMITED ENGLISH PROFICIENCY; BLOOD-PRESSURE CONTROL; BODY-MASS INDEX; MEXICAN-AMERICANS; UNITED-STATES; HEALTH-CARE; SAN-ANTONIO; RACIAL/ETHNIC DIFFERENCES; PHYSICAL-ACTIVITY AB The prevalence of type 2 diabetes mellitus is higher in Hispanic/Latino individuals living in the United States compared with their non-Hispanic white counterparts. Many factors contribute to the increased prevalence of type 2 diabetes, including biological characteristics, socioeconomic conditions, and cultural aspects. The contribution of genetics to the risk of type 2 diabetes in Hispanic/Latino patients is becoming increasingly clear, but this inherent risk factor cannot be modified. However, certain socioeconomic and cultural factors, such as reduced access to healthcare, language barriers, cultural beliefs, and lack of cultural competence by the healthcare provider, are modifiable and should be overcome in order to improve the management of type 2 diabetes in Hispanic/Latino patients. At the healthcare system level, policies should be put into place to reduce disparities between Hispanics/Latinos and non-Hispanic whites regarding health insurance coverage and access to healthcare. At the healthcare provider and patient level, cultural beliefs should be taken into consideration when selecting adequate treatment. Overall, type 2 diabetes management should be individualized by identifying the preferred language and level of acculturation for each patient. These considerations are necessary to further improve communication through culturally appropriate educational materials and programs. These strategies may help to overcome the barriers in the treatment of type 2 diabetes in Hispanic/Latino patients. (C) 2011 Elsevier Inc. All rights reserved. The American Journal of Medicine (2011) 124, S16-S21 C1 [Cersosimo, Eugenio; Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Texas Diabet Inst, San Antonio, TX 78229 USA. [Musi, Nicolas] Audie L Murphy Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. RP Cersosimo, E (reprint author), 701 S Zarzamora,MS 10-5, San Antonio, TX 78284 USA. EM Eugenio.Cersosimo@uhs-sa.com FU Daiichi Sankyo, Inc. FX Medical writing services and editorial assistance provided by Karen Stauffer, PhD, and Lucy Whitehouse, of inScience Communications, a Wolters Kluwer business, were funded by Daiichi Sankyo, Inc. NR 46 TC 6 Z9 6 U1 2 U2 18 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 OCT PY 2011 VL 124 IS 10 SU 1 BP S16 EP S21 DI 10.1016/j.amjmed.2011.07.019 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 825GD UT WOS:000295258300004 PM 21939794 ER PT J AU Hamilton, BE Nesbit, GM Dosa, E Gahramanov, S Rooney, B Nesbit, EG Raines, J Neuwelt, EA AF Hamilton, Bronwyn E. Nesbit, Gary M. Dosa, Edit Gahramanov, Seymur Rooney, Bill Nesbit, Eric G. Raines, Joshua Neuwelt, Edward A. TI Comparative Analysis of Ferumoxytol and Gadoteridol Enhancement Using T1-and T2-Weighted MRI in Neuroimaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE contrast agents; glial neoplasms; iron oxide nanoparticles; nephrogenic systemic fibrosis; ultrasmall superparamagnetic iron oxides ID CENTRAL-NERVOUS-SYSTEM; CONTRAST AGENT; BRAIN-TUMORS; FERUMOXTRAN-10; NANOPARTICLES; FERUMOXIDES AB OBJECTIVE. Ferumoxytol, an ultrasmall superparamagnetic iron oxide particle, has been suggested as a potential alternative MRI contrast agent in patients with renal failure. We compared ferumoxytol to gadoteridol enhancement on T1- and T2-weighted MRI in CNS disorders to explore its diagnostic utility. SUBJECTS AND METHODS. Data were collected from three protocols in 70 adults who underwent alternate-day gadoteridol-and ferumoxytol-enhanced MRI using identical parameters. Two neuroradiologists measured lesion-enhancing size and intensity on contrast-enhanced T1-weighted images in consensus. T2-weighted images were evaluated for the presence of contrast-enhanced hypointensity. Mixed model repeated measures analysis of variance determined differences between T1-weighted enhancement size and intensity for individual protocols and group. RESULTS. After exclusions, 49 MRI studies in 29 men and 20 women (mean age, 51 years) were assessed. T1-weighted estimated enhancing sizes were different between agents (p = 0.0456) as a group; however, no differences were observed with untreated gliomas (n = 17) in two protocols (p = 1.0 and p = 0.99, respectively). Differences in T1-weighted enhancement intensity between agents were significant for the group overall (p = 0.0006); however, three-way interactions were not significant (p = 0.1233). T2-weighted images were assessed for contrast-enhanced hypointensity, observed in 26 of 49 (53%) ferumoxytol and zero of 49 (0%) gadoteridol scans. CONCLUSION. Ferumoxytol may be a useful MRI contrast agent in patients who are unable to receive gadolinium-based contrast agents. Greater experience with a wider variety of disorders is necessary to understand differences in enhancement with ferumoxytol compared with gadolinium-based contrast agents, given their different mechanisms of action. C1 [Hamilton, Bronwyn E.; Nesbit, Gary M.; Nesbit, Eric G.] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97239 USA. [Dosa, Edit; Gahramanov, Seymur; Raines, Joshua; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Rooney, Bill] Oregon Hlth & Sci Univ, Adv Imaging Res Lab, Portland, OR 97239 USA. [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97239 USA. [Neuwelt, Edward A.] Portland VA Med Ctr, Portland, OR USA. RP Hamilton, BE (reprint author), Oregon Hlth & Sci Univ, Dept Radiol, 3181 SW Sam Jackson Pk Rd,Mail Code CR 135, Portland, OR 97239 USA. EM hamiltob@ohsu.edu FU National Institutes of Health [NS44687, NS53468, CA137488]; Department of Veterans Affairs FX This research was funded in part by the National Institutes of Health (grants NS44687, NS53468, and CA137488) and by a Veterans Affairs Merit Review grant from the Department of Veterans Affairs to E. A. Neuwelt. NR 19 TC 32 Z9 32 U1 1 U2 11 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 OCT PY 2011 VL 197 IS 4 BP 981 EP 988 DI 10.2214/AJR.10.5992 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 822WL UT WOS:000295081000072 PM 21940589 ER PT J AU Peterson, CL Kautz, SA Neptune, RR AF Peterson, Carrie L. Kautz, Steven A. Neptune, Richard R. TI Muscle work is increased in pre-swing during hemiparetic walking SO CLINICAL BIOMECHANICS LA English DT Article DE Post-stroke; Mechanical work; Simulation; Three-dimensional; Biomechanics ID MECHANICAL WORK; ENERGY-COST; LOWER-EXTREMITY; MOTOR CONTROL; STROKE; GAIT; SPEED; MODEL; DETERMINANTS; PROPULSION AB Background: Muscle mechanical work is likely affected by gait abnormalities in hemiparetic walking during the paretic pre-swing phase (i.e., double support phase preceding paretic toe-off). Previous experimental studies suggest that muscle work may be decreased in the paretic leg, but paretic work may have been underestimated since experimental approaches based on net joint moments do not account for co-contraction of antagonist muscles. Also, whether the non-paretic leg does more work compared to control subjects at matched speeds and how work generation may differ between hemiparetic subjects walking with different self-selected speeds remains unknown. Methods: Three-dimensional forward dynamics simulations of two representative hemiparetic subjects walking with different self-selected speeds (i.e.. limited community = 0.45 m/s and community walkers = 0.9 m/s) and a speed and age-matched control subject were generated to quantify musculotendon (fiber and in-series tendon) work during paretic pre-swing. Findings: Total paretic and non-paretic fiber work were increased in both the limited community and community hemiparetic walkers compared to the control. Increased fiber work in the limited community walker was primarily related to decreased fiber and tendon work by the paretic plantar flexors requiring compensatory work by other muscles. Increased fiber work in the community walker was primarily related to increased work by the hip abductors and adductors. Interpretation: The hemiparetic walkers would expend more metabolic energy during pre-swing if the hemiparetic and control subjects were to perform work with the same mechanical efficiency. These results may partly explain the increased metabolic cost of hemiparetic walkers compared to nondisabled walkers at matched speeds. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Peterson, Carrie L.; Neptune, Richard R.] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. [Kautz, Steven A.] Malcom Randall VA Med Ctr, Brain Rehabil Res Ctr, Gainesville, FL USA. [Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Kautz, Steven A.] Med Univ S Carolina, Dept Hlth Sci & Res, Div Phys Therapy, Charleston, SC 29425 USA. RP Neptune, RR (reprint author), Univ Texas Austin, Dept Mech Engn, 1 Univ Stn C2200, Austin, TX 78712 USA. EM rneptune@mail.utexas.edu RI Peterson, Carrie/C-6007-2016 OI Peterson, Carrie/0000-0002-7169-2089; Kautz, Steven/0000-0003-3151-8235 FU NIH [RO1 HD46820]; Rehabilitation Research & Development Service of the VA; NSF FX This work was funded by NIH grant RO1 HD46820, the Rehabilitation Research & Development Service of the VA and a NSF Graduate Research Fellowship. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NICHD, VA or United States Government. NR 38 TC 9 Z9 9 U1 0 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD OCT PY 2011 VL 26 IS 8 BP 859 EP 866 DI 10.1016/j.clinbiomech.2011.04.010 PG 8 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 822TR UT WOS:000295073000011 PM 21605927 ER PT J AU Patel, SG Ahnen, DJ AF Patel, Swati G. Ahnen, Dennis J. TI Isn't It Time to Stop Talking About Colonoscopy Quality and Start Doing Something About It? SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material ID COLORECTAL-CANCER; NEGATIVE COLONOSCOPY; ENDOSCOPIST; PREVENTION; RISK C1 [Patel, Swati G.; Ahnen, Dennis J.] Denver VA Med Ctr, Div Gastroenterol, Dept Med, Denver, CO 80220 USA. [Patel, Swati G.; Ahnen, Dennis J.] Univ Colorado, Sch Med, Denver, CO USA. RP Ahnen, DJ (reprint author), Denver VA Med Ctr, Div Gastroenterol, Dept Med, Denver, CO 80220 USA. EM dennis.ahnen@ucdenver.edu NR 18 TC 3 Z9 3 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 OCT PY 2011 VL 56 IS 10 BP 2776 EP 2779 DI 10.1007/s10620-011-1860-2 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 823YP UT WOS:000295164600019 PM 21863330 ER PT J AU Solomon, M Bonafede, M Pan, K Wilson, K Beam, C Chakravarti, P Spiegel, B AF Solomon, M. Bonafede, M. Pan, K. Wilson, K. Beam, C. Chakravarti, P. Spiegel, B. TI Direct Medical Care Costs Among Pegylated Interferon Plus Ribavirin-Treated and Untreated Chronic Hepatitis C Patients SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Hepatitis C; Pegylated interferon; Burden of illness; Administrative claims database analysis ID QUALITY-OF-LIFE; BURDEN; MANAGEMENT; INFECTION; ILLNESS; DISEASE AB Hepatitis C virus (HCV) is a common and expensive infectious disease. The current standard of care for HCV infection, pegylated interferon with ribavirin (PEG-RBV), is costly and has a significant adverse event profile. To quantify the direct economic burden of HCV infection and PEG-RBV treatment for HCV. Using a large administrative claims database, we evaluated the medical and prescription drug costs of patients with HCV from 2002 to 2007. A cohort of patients with PEG-RBV was 1:1 propensity score-matched to a cohort of untreated HCV patients. Multivariate models adjusted for demographic and clinical characteristics in evaluating the effect of PEG-RBV treatment on direct medical expenditure. The matched analysis included 20,002 patients. PEG-RBV-treated patients had higher total direct medical costs ($28,547 vs. $21,752; P < 0.001), outpatient pharmacy costs ($17,419 vs. $2,900; P < 0.001), and outpatient physician visit costs ($894 vs. $787; P < 0.001), but lower inpatient costs ($3,942 vs. $9,543; P < 0.001) and emergency room costs ($366 vs. $505; P < 0.001). After multivariate adjustment, PEG-RBV use was associated with an additional $9,423 in total direct medical costs and an additional $12,244 in HCV-related total medical costs. Total HCV-related medical costs are higher for treated than untreated patients, driven mostly by higher outpatient pharmacy costs, which outweigh higher HCV-related inpatient costs incurred by untreated patients. C1 [Spiegel, B.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Chakravarti, P.] Novartis Pharmaceut, E Hanover, NJ USA. [Beam, C.] Human Genome Sci Inc, Rockville, MD USA. [Bonafede, M.; Pan, K.; Wilson, K.] Thomson Reuters Healthcare, Cambridge, MA USA. [Solomon, M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Spiegel, B (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU Human Genome Sciences; Novartis Pharmaceuticals Corporation; Thomson Reuters FX This study was funded in full by Human Genome Sciences and Novartis Pharmaceuticals Corporation, which employs Cynthia Beam and Paula Chakravarti, respectively. Thomson Reuters was awarded a contract to conduct the study and is the employer of Machaon Bonafede, Katy Pan, and Kathleen Wilson. Brennan Spiegel and Matthew Solomon received funding from Human Genome Sciences to serve as consultants in support of the study. NR 24 TC 10 Z9 10 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2011 VL 56 IS 10 BP 3024 EP 3031 DI 10.1007/s10620-011-1802-z PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 823YP UT WOS:000295164600051 PM 21717127 ER PT J AU Michaelis, KA Knox, AJ Xu, M Kiseljak-Vassiliades, K Edwards, MG Geraci, M Kleinschmidt-DeMasters, BK Lillehei, KO Wierman, ME AF Michaelis, Katherine A. Knox, Aaron J. Xu, Mei Kiseljak-Vassiliades, Katja Edwards, Michael G. Geraci, Mark Kleinschmidt-DeMasters, B. K. Lillehei, Kevin O. Wierman, Margaret E. TI Identification of Growth Arrest and DNA-Damage-Inducible Gene beta (GADD45 beta) as a Novel Tumor Suppressor in Pituitary Gonadotrope Tumors SO ENDOCRINOLOGY LA English DT Article ID INHIBITORY GENE; P53 PROTEIN; ADENOMAS; EXPRESSION; PROLIFERATION; TUMORIGENESIS; GADD45-GAMMA; INVASION; CANCER; CARCINOMAS AB Gonadotrope and null cell pituitary tumors cause significant morbidity, often presenting with signs of hypogonadism together with visual disturbances due to mass effects. Surgery and radiation are the only therapeutic options to date. To identify dysregulated genes and pathways that may play a role in tumorigenesis and/or progression, molecular profiling was performed on 14 gonadotrope tumors, with nine normal human pituitaries obtained at autopsy serving as controls. Bioinformatic analysis identified putative downstream effectors of tumor protein 53 (p53) that were consistently repressed in gonadotrope pituitary tumors, including RPRM, P21, and PMAIP1, with concomitant inhibition of the upstream p53 regulator, PLAGL1(Zac1). Further analysis of the growth arrest and DNA damage-inducible (GADD45) family revealed no change in the p53 target, GADD45 alpha, but identified repression of GADD45 beta in pituitary tumors in addition to the previously reported inhibition of GADD45 gamma. Overexpression of GADD45 beta in L beta T2 mouse gonadotrope cells blocked tumor cell proliferation and increased rates of apoptosis in response to growth factor withdrawal. Stable gonadotrope cell transfectants expressing increased GADD45 beta showed decreased colony formation in soft agar, confirming its normal role as a tumor suppressor. Unlike previous studies of GADD45 gamma in pituitary tumors and alpha and beta in other tumors, bisulfite sequencing showed no evidence of hypermethylation of the GADD45 beta promoter in human pituitary tumor samples to explain the repression of its expression. Thus, GADD45 beta is a novel pituitary tumor suppressor whose reexpression blocks proliferation, survival, and tumorigenesis. Together these studies identify new targets and mechanisms to explore in pituitary tumor initiation and progression. (Endocrinology 152: 3603-3613, 2011) C1 [Michaelis, Katherine A.; Knox, Aaron J.; Xu, Mei; Kiseljak-Vassiliades, Katja; Edwards, Michael G.; Geraci, Mark; Wierman, Margaret E.] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA. [Kleinschmidt-DeMasters, B. K.] Univ Colorado Denver, Dept Pathol, Aurora, CO 80045 USA. [Lillehei, Kevin O.] Univ Colorado Denver, Dept Neurosurg, Aurora, CO 80045 USA. [Xu, Mei; Kiseljak-Vassiliades, Katja; Wierman, Margaret E.] Denver Vet Affairs Med Ctr, Res Serv, Denver, CO 80220 USA. RP Wierman, ME (reprint author), Univ Colorado, Sch Med, Vet Affairs Med Ctr Endo 111H, 1055 Clermont St, Denver, CO 80220 USA. EM Margaret.Wierman@ucdenver.edu FU Veterans Affairs Merit Review FX This work was supported by Veterans Affairs Merit Review to M.E.W. NR 42 TC 42 Z9 45 U1 0 U2 10 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 OCT PY 2011 VL 152 IS 10 BP 3603 EP 3613 DI 10.1210/en.2011-0109 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 822WN UT WOS:000295081200005 PM 21810943 ER PT J AU Etzel, JP Larson, MF Anawalt, BD Collins, J Dominitz, JA AF Etzel, Jason P. Larson, Meaghan F. Anawalt, Bradley D. Collins, Judith Dominitz, Jason A. TI Assessment and Management of Low Bone Density in Inflammatory Bowel Disease and Performance of Professional Society Guidelines SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE inflammatory bowel disease; osteoporosis; guideline; hypogonadism ID POPULATION-BASED COHORT; MINERAL DENSITY; CROHNS-DISEASE; ULCERATIVE-COLITIS; FRACTURE RISK; FRAGILITY FRACTURE; CORTICOSTEROID USE; OLMSTED COUNTY; OSTEOPOROSIS; DIAGNOSIS AB Background: Inflammatory bowel disease (IBD) patients have increased prevalence of osteoporosis, leading to guideline recommendations for bone mineral density (BMD) testing. The study aim was to identify predictors of BMD testing and treatment and assess guideline effectiveness to identify IBD patients with osteoporosis. Methods: Records of all IBD patients at seven medical facilities were reviewed for clinical data and BMD testing from January 1996 through October 2006. Results: A total of 2035 patients had 317 bone density tests performed. Osteopenia was found in 48% of patients, osteoporosis in 26%. Among patients meeting guideline criteria for BMD testing and >= 1 year of follow-up, 23.3% underwent testing. The strongest predictors of testing were menopause (adjusted hazard ratio [AHR] 3.02) and receiving care at a tertiary center (AHR 2.56). Testing rates were low in patients with age >= 60 years, ulcerative colitis, and a history of inpatient IBD treatment. Osteoporotic patients received calcium/vitamin D and bisphosphonates in 59% and 75% of cases, respectively. Osteoporotic males had a 37% rate of hypogonadism. Guideline criteria do not distinguish patients with osteoporosis. The criteria had a sensitivity, specificity, positive predictive value, and negative predictive value of 84%, 23%, 27%, and 81% for osteoporosis in the tested population, respectively. Conclusions: Osteoporosis is highly prevalent in the IBD population, but BMD testing and osteoporosis treatments are underutilized. Male hypogonadism is common in osteoporotic IBD patients. Guidelines do not identify IBD patients with osteoporosis. C1 [Etzel, Jason P.; Collins, Judith] Oregon Hlth & Sci Univ, Dept Med, Div Gastroenterol, Portland, OR 97201 USA. [Larson, Meaghan F.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Anawalt, Bradley D.] Univ Washington, Sch Med, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. [Dominitz, Jason A.] VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Dominitz, Jason A.] Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. RP Dominitz, JA (reprint author), VAPSHCS S 111 GI, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Jason.Dominitz@va.gov OI Dominitz, Jason/0000-0002-8070-7086 FU VA Puget Sound Health Care System, Seattle, Washington FX There was no funding for this study. This material is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, Washington. The views and opinions of the authors expressed herein do not necessarily state or reflect those of the United States Government or the Department of Veterans Affairs. The authors have no conflicts of interest to disclose. NR 38 TC 25 Z9 27 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD OCT PY 2011 VL 17 IS 10 BP 2122 EP 2129 DI 10.1002/ibd.21601 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 823RF UT WOS:000295140800017 PM 21910174 ER PT J AU Chua, SL Maurer, T Chren, MM AF Chua, Ser Ling Maurer, Toby Chren, Mary-Margaret TI Adaptation of a Runyankore version of Skindex-16 for oral administration in Mbarara, Uganda SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID QUALITY-OF-LIFE; SKIN DISEASES; CULTURAL-ADAPTATION; RELIABILITY; VALIDITY; ALPHA AB Background Health-related quality of life instruments are typically developed and validated for use in developed countries by patients who can read and write. Little is known about the feasibility of using adaptations of validated instruments in situations where literacy rates are low. Objective We aimed to translate, culturally adapt, and test an oral version of Skindex-16 in Runyankore, the predominant language in Mbarara, Uganda, for use in dermatologic research. Methods Skindex-16 was forward-and back-translated to Runyankore. The Runyankore version was administered orally to 47 dermatology patients and 47 random hospital visitors. Additional questions regarding duration, dyspigmentation, concealment status of the skin problem, and overall quality of life effect were also asked. Results Oral delivery was feasible; <= 10 minutes per subject. High Cronbach alpha values (0.86, 0.88, and 0.85 for symptoms, emotions, and functioning subscales, respectively) demonstrated internal consistency reliability. As hypothesized, subjects with reported skin problems, dyspigmentation, and difficulty in concealment had higher mean Skindex scores. A total of 72.4% of responses to the open-ended question were addressed in Skindex-16, indicating content validity. Conclusion The orally delivered Runyankore version of Skindex-16 is reliable, with construct and content validity, and feasible for use in dermatology research in Mbarara, Uganda. Orally administered quality of life instruments have potential for use in low literacy groups worldwide. C1 [Chua, Ser Ling; Maurer, Toby; Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94110 USA. [Chren, Mary-Margaret] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program, San Francisco, CA USA. [Chua, Ser Ling] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Dermatol, San Francisco, CA 94110 USA. RP Chua, SL (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Dept Dermatol, 1001 Potrero Ave, San Francisco, CA 94110 USA. EM schua@doctors.org.uk FU British Association of Dermatologists; National Institute of Health [K24 AR052667] FX We would like to thank the investigators and staff of the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort, a collaboration between University of California, San Francisco, Harvard and Mbarara University of Science and Technology in Uganda, for making this study possible. SLC was supported by the Roger Harman African Travelling Fellowship from the British Association of Dermatologists. MMC was supported by a grant from the National Institute of Health (K24 AR052667). NR 17 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD OCT PY 2011 VL 50 IS 10 BP 1249 EP 1254 DI 10.1111/j.1365-4632.2011.04894.x PG 6 WC Dermatology SC Dermatology GA 824BY UT WOS:000295176300009 PM 21950290 ER PT J AU Dennehy, EB Marangell, LB Allen, MH Chessick, C Wisniewski, SR Thase, ME AF Dennehy, Ellen B. Marangell, Lauren B. Allen, Michael H. Chessick, Cheryl Wisniewski, Stephen R. Thase, Michael E. TI Suicide and suicide attempts in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar disorder; Suicide; Suicide attempt ID MOOD DISORDERS; RISK-FACTORS; COMPLETED SUICIDE; FOLLOW-UP; COMORBIDITY; MORTALITY; PREDICTORS; BEHAVIOR AB Background: The current report describes individuals with bipolar disorder who attempted or completed suicide while participating in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study. Methods: Baseline and course features of individuals with suicide events are described. Results: Among the 4360 people with bipolar disorder enrolled, 182 individuals made 270 prospectively observed suicidal acts, including 8 completed suicides. This represents a suicide rate of .014 per 100 person years in STEP-BD. which included frequent clinical visits, evidence based care, and standardized assessment at each patient contact. Approximately 1/3 of those who attempted suicide had more than one attempt during study participation. Those who completed suicide tended to do so early in study participation, and half of them did so on their first attempt. Limitations: While this study is limited to description of individuals and precipitants of completed suicides and attempts in STEP-BD, further analyses are planned to explore risk factors and potential interventions for prevention of suicidal acts in persons with bipolar disorder. Conclusions: Persons with bipolar disorder are at high risk for suicide. Overall rates of suicide events in STEP-BD were lower than expected, suggesting that the combination of frequent clinical visits (i.e.. access to care), standardized assessment, and evidence-based treatment were helpful in this population. (C) 2011 Elsevier B.V. All rights reserved. C1 [Dennehy, Ellen B.] Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. [Marangell, Lauren B.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Marangell, Lauren B.] Baylor Coll Med, Mood Disorders Ctr, Menninger Dept Psychiat, Houston, TX 77030 USA. [Marangell, Lauren B.] US Dept Vet Affairs, Houston, TX USA. [Allen, Michael H.; Chessick, Cheryl] Univ Colorado, Denver Depress Ctr, Denver, CO 80202 USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA USA. [Thase, Michael E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Dennehy, EB (reprint author), Purdue Univ, Dept Psychol Sci, 703 3rd St, W Lafayette, IN 47907 USA. EM edennehy@purdue.edu RI Allen, Michael/A-8776-2011 OI Wisniewski, Stephen/0000-0002-3877-9860 FU National Institute of Mental Health (NIMH), National Institutes of Health [N01MH80001] FX The STEP-BD study was conducted with federal funds from the National Institute of Mental Health (NIMH), National Institutes of Health, under Contract N01MH80001. NIMH had no role in study design. An NIMH staff member was a member of the committee that reviewed all reported suicide events; decisions whether deaths were coded as a suicide were determined in some cases by a death certificate, and in some cases by the presence of a clear suicide note or other evidence in support of clear suicidal intention. Ruling of whether events were coded as a suicide attempts were based on patient self report, evidence of self-harm and/or evidence of clear intent for self-harm, and were based on consensus of the committee members. Other than that, NIMH staff had no involvement 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 31 TC 26 Z9 27 U1 4 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT PY 2011 VL 133 IS 3 BP 423 EP 427 DI 10.1016/j.jad.2011.04.036 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 823HB UT WOS:000295112000008 PM 21601286 ER PT J AU Leung, F Leung, J Siao-Salera, R Mann, S Ramirez, F Friedland, S Amato, A Radaelli, F Hsieh, YH AF Leung, F. Leung, J. Siao-Salera, R. Mann, S. Ramirez, F. Friedland, S. Amato, A. Radaelli, F. Hsieh, Y-H TI Removal of infused water predominantly during insertion (water exchange) is consistently associated with a greater reduction of pain score - review of data in RCTs of water method colonoscopy SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Meeting Abstract C1 [Leung, F.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Sacramento, CA USA. [Leung, F.] David Geffen Sch Med Ucla, Sacramento, CA USA. [Leung, J.; Mann, S.] Uc Davis Med Ctr, Vanchcs, Sacramento Vamc, Sacramento, CA USA. [Siao-Salera, R.] Vanchcs, Sacramento Vamc, Mather, CA USA. [Ramirez, F.] Mayo Clin, Scottsdale, AZ USA. [Friedland, S.] Stanford Univ, Palo Alto Vamc, Palo Alto, CA 94304 USA. [Amato, A.] Valduce Hosp, Como, Italy. [Radaelli, F.; Hsieh, Y-H] Buddhist Dalin Tzu Chi Gen Hosp, Chiayi, Taiwan. 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 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD OCT PY 2011 VL 26 SU 5 SI SI BP 128 EP 129 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 823CG UT WOS:000295099200346 ER PT J AU Mizukami, K Ishikawa, M Akatsu, H Abrahamson, EE Ikonomovic, MD Asada, T AF Mizukami, Katsuyoshi Ishikawa, Masanori Akatsu, Hiroyasu Abrahamson, Eric E. Ikonomovic, Milos D. Asada, Takashi TI An immunohistochemical study of the serotonin 1A receptor in the hippocampus of subjects with Alzheimer's disease SO NEUROPATHOLOGY LA English DT Article DE Alzheimer's disease; hippocampus; immunohistochemistry; neurofibrillary tangle; serotonin 1A receptor ID MILD COGNITIVE IMPAIRMENT; 5-HT1A RECEPTORS; RAT-BRAIN; DEMENTIA; NEURONS; BINDING; 5-HYDROXYTRYPTAMINE(1A); ACETYLCHOLINE; LOCALIZATION; GLUTAMATE AB Alzheimer's disease (AD) is associated with neuronal degeneration, synaptic loss and deficits in multiple neurotransmitter systems. Alterations in the serotonin 1A (5-HT1A) receptor can contribute to impaired cognitive function in AD, and both in vitro binding and Positron emission tomography (PET) imaging studies have demonstrated that 5-HT1A receptors in the hippocampus/medial temporal cortex are affected early in AD. This neuropathological study examined the localization and immunoreaction intensity of 5-HT1A receptor protein in AD hippocampus with the goal to determine whether neuronal receptor levels are influenced by the severity of NFT severity defined by Braaks' pathological staging and to provide immunohistochemical confirmation of the binding assays and PET imaging studies. Subjects included AD patients and non-AD controls (NC) stratified into three Braaks' stages (Braak 0-II, NC; Braak III/IV and V/VI, AD). In the Braak 0-II group, 5-HT1A-immunoreactivity (ir) was prominent in the neuropil of the CA1 and subiculum, moderate in the dentate gyrus molecular layer (DGml), and low in the CA3 and CA4. No changes in 5-HT1A-ir were observed in the hippocampus of AD subjects in the Braak III/IV group. Hippocampal 5-HT1A-ir intensity was markedly decreased in the CA1 region in 6/11 (54.5%) subjects in the Braak V/VI group. Across all three groups combined, there was a statistically significant association between reduced 5HT1A-ir and neuronal loss in the CA1, but not in the CA3. The present data demonstrate that hippocampal 5-HT1A receptors are mainly preserved until the end-stage of NFT progression in AD. Thus, the utility of PET imaging using a 5-HT1A-specific radiolabeled probe as a marker of hippocampal neuronal loss may be limited to the CA1 field in advanced stage AD cases. C1 [Mizukami, Katsuyoshi; Ishikawa, Masanori; Asada, Takashi] Univ Tsukuba, Inst Clin Med, Dept Psychiat, Tsukuba, Ibaraki 3058575, Japan. [Akatsu, Hiroyasu] Fukushimura Hosp, Choju Med Inst, Aichi, Japan. [Abrahamson, Eric E.; Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15260 USA. RP Mizukami, K (reprint author), Univ Tsukuba, Inst Clin Med, Dept Psychiat, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan. EM mizukami@md.tsukuba.ac.jp FU NIH [NIA AG05133, AG14449]; Snee-Reinhardt Charitable Foundation; Japanese Ministry of Education, Culture, Sports, Science and Technology; ADRC at the University of Pittsburgh FX We are indebted to the support of the participants in the ADRC at the University of Pittsburgh. This study was supported by NIH grants NIA AG05133 (University of Pittsburgh ADRC), and AG14449 (MDI), The Snee-Reinhardt Charitable Foundation (MDI), and by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (KM). Ms. Suganya Srinivasan, Ms. Natsuko Kato and Ms. Megumi Mitani provided expert technical assistance. NR 31 TC 6 Z9 6 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0919-6544 J9 NEUROPATHOLOGY JI Neuropathology PD OCT PY 2011 VL 31 IS 5 BP 503 EP 509 DI 10.1111/j.1440-1789.2010.01193.x PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 823SK UT WOS:000295145500006 PM 21269332 ER PT J AU Zite, N Borrero, S AF Zite, Nikki Borrero, Sonya TI Female sterilisation in the United States SO EUROPEAN JOURNAL OF CONTRACEPTION AND REPRODUCTIVE HEALTH CARE LA English DT Review DE Tubal sterilisation; Hysteroscopic sterilisation; Contraception; Family planning; United States ID TUBAL-STERILIZATION; CONTRACEPTIVE STERILIZATION; HYSTEROSCOPIC STERILIZATION; PREGNANCY; RATES; WOMEN; RISK AB Female sterilisation is a safe and effective form of permanent birth control. In the United States (US), it is still the second most commonly used form of contraception overall and is the most frequently used method among married women and among women over 30 years of age. Although several European countries have noted a sharp decline in the number of women electing tubal sterilisation in recent years, such trends have not been as obvious in the US. While female sterilisation remains popular, there are considerable system-level barriers to getting the procedure for certain segments of the population as well as emerging concerns about appropriate utilisation of this contraceptive method in light of newer, reversible options and the knowledge that regret after permanent contraception is high. Given the complexity of this decision-making process, it is critical that providers ensure at the very least that women are aware of the potential disadvantages of tubal occlusion and are knowledgeable of other highly effective contraceptive methods that are available but vastly underutilised in the US, namely, vasectomy, intrauterine contraceptives, and implants. C1 [Zite, Nikki] Univ Tennessee, Grad Sch Med, Dept Obstet & Gynecol, Knoxville, TN 37920 USA. [Borrero, Sonya] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Zite, N (reprint author), Univ Tennessee, Grad Sch Med, Dept Obstet & Gynecol, 1928 Alcoa Highway,Suite 118, Knoxville, TN 37920 USA. EM nzite@mc.utmck.edu FU National Center for Research Resources (NCRR) [05 KL2 RR024154-05]; National Institutes of Health (NIH) FX Dr Borrero is funded by 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. The content of this publication is solely the responsibility of the authors and it does not necessarily represent the official view of NCRR or NIH. NR 24 TC 7 Z9 7 U1 1 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1362-5187 J9 EUR J CONTRACEP REPR JI Eur. J. Contracept. Reprod. Health Care PD OCT PY 2011 VL 16 IS 5 BP 336 EP 340 DI 10.3109/13625187.2011.604451 PG 5 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology SC Public, Environmental & Occupational Health; Obstetrics & Gynecology GA 821WC UT WOS:000295004100003 PM 21848391 ER PT J AU Dutz, J Werth, VP AF Dutz, Jan Werth, Victoria P. TI Cigarette Smoking and Response to Antimalarials in Cutaneous Lupus Erythematosus Patients: Evolution of a Dogma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID BLOOD HYDROXYCHLOROQUINE; RHEUMATOID-ARTHRITIS; SEVERITY INDEX; DISEASE AREA; INSTRUMENT; THERAPY; LESIONS; MARKER; DRUGS; CLASI AB Antimalarial agents ameliorate disease in more than half of patients with cutaneous lupus erythematosus (CLE), regardless of smoking status. The major determinant of responsiveness appears to be severity: more extensive CLE and CLE in the setting of systemic lupus erythematosus (SLE) respond less well to antimalarial therapy. Prospective studies are needed to determine whether antimalarials are more likely to benefit patients smokers and nonsmokers who have milder cutaneous lupus. Agreement on a single, validated disease severity measure for CLE would permit comparisons among studies and thereby foster progress in the field. C1 [Werth, Victoria P.] Univ Penn, Sch Med, Dept Dermatol, Perelman Ctr Adv Med, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Dutz, Jan] Univ British Columbia, Dept Dermatol & Skin Sci, Child & Family Res Inst, Vancouver, BC V5Z 1M9, Canada. RP Werth, VP (reprint author), Univ Penn, Sch Med, Dept Dermatol, Perelman Ctr Adv Med, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU NIAMS NIH HHS [K24-AR 18 02207, K24 AR002207-09, K24 AR002207] NR 24 TC 8 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2011 VL 131 IS 10 BP 1968 EP 1970 DI 10.1038/jid.2011.237 PG 3 WC Dermatology SC Dermatology GA 822RV UT WOS:000295068200002 PM 21918570 ER PT J AU Keedy, AW Yee, J Aslam, R Weinstein, S Landeras, LA Shah, JN McQuaid, KR Yeh, BM AF Keedy, Alexander W. Yee, Judy Aslam, Rizwan Weinstein, Stefanie Landeras, Luis A. Shah, Janak N. McQuaid, Kenneth R. Yeh, Benjamin M. TI Reduced Cathartic Bowel Preparation for CT Colonography: Prospective Comparison of 2-L Polyethylene Glycol and Magnesium Citrate SO RADIOLOGY LA English DT Article ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; LOW-FIBER DIET; COLORECTAL-CANCER; PATIENT ACCEPTANCE; SODIUM-PHOSPHATE; CONTROLLED-TRIAL; PERFORMANCE-CHARACTERISTICS; DIAGNOSTIC PERFORMANCE; COLONOSCOPY; VOLUME AB Purpose: To prospectively compare adequacy of colonic cleansing, adequacy of solid stool and fluid tagging, and patient acceptance by using reduced-volume, 2-L polyethylene glycol (PEG) versus magnesium citrate bowel preparations for CT colonography. Materials and Methods: This study was approved by the institutional Committee on Human Research and was compliant with HIPAA; all patients provided written consent. In this randomized, investigator-blinded study, 50 patients underwent oral preparation with either a 2-L PEG or a magnesium citrate solution, tagging with oral contrast agents, and subsequent CT colonography and segmentally unblinded colonoscopy. The residual stool (score 0 [best] to 3 [worst]) and fluid (score 0 [best] to 4 [worst]) burden and tagging adequacy were qualitatively assessed. Residual fluid attenuation was recorded as a quantitative measure of tagging adequacy. Patients completed a tolerance questionnaire within 2 weeks of scanning. Preparations were compared for residual stool and fluid by using generalized estimating equations; the Mann-Whitney test was used to compare the qualitative tagging score, mean residual fluid attenuation, and adverse effects assessed on the patient experience questionnaire. Results: The mean residual stool (0.90 of three) and fluid burden (1.05 of four) scores for PEG were similar to those for magnesium citrate (0.96 [P = .58] and 0.98 [P = .48], respectively). However, the mean fecal and fluid tagging scores were significantly better for PEG (0.48 and 0.28, respectively) than for magnesium citrate (1.52 [P < .01] and 1.28 [P < .01], respectively). Mean residual fluid attenuation was higher for PEG (765 HU) than for magnesium citrate (443 HU, P = .01), and mean interpretation time was shorter for PEG (14.8 minutes) than for magnesium citrate (18.0 minutes, P = .04). Tolerance ratings were not significantly different between preparations. Conclusion: Reduced-volume PEG and magnesium citrate bowel preparations demonstrated adequate cleansing effectiveness for CT colonography, with better tagging and shorter interpretation time observed in the PEG group. Adequate polyp detection was maintained but requires further validation because of the small number of clinically important polyps. C1 [Keedy, Alexander W.; Yee, Judy; Aslam, Rizwan; Weinstein, Stefanie; Landeras, Luis A.; Shah, Janak N.; McQuaid, Kenneth R.; Yeh, Benjamin M.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, VAMC, Dept Radiol, San Francisco, CA 94143 USA. RP Yee, J (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, VAMC, Dept Radiol, 4150 Clement St,Box 114, San Francisco, CA 94143 USA. EM Judy.Yee@radiology.ucsf.edu FU National Institutes of Health [UL1 RR024131] FX This research was supported by the National Institutes of Health (grant UL1 RR024131). NR 44 TC 8 Z9 9 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2011 VL 261 IS 1 BP 156 EP 164 DI 10.1148/radiol.11110217 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 822IW UT WOS:000295039000017 PM 21873253 ER PT J AU Shin, JM Munson, K Sachs, G AF Shin, Jai Moo Munson, Keith Sachs, George TI Gastric H+,K+-ATPase SO COMPREHENSIVE PHYSIOLOGY LA English DT Article AB The gastric H+, K+-ATPase is responsible for gastric acid secretion. This ATPase is composed of two subunits, the catalytic alpha subunit and the structural beta subunit. The alpha subunit with molecular mass of about 100 kDa has 10 transmembrane domains and is strongly associated with the beta subunit with a single transmembrane segment and a peptide mass of 35 kDa. Its three-dimensional structure is based on homology modeling and site-directed mutagenesis resulting in a proton extrusion and K+ reabsorption model. There are three conserved H3O+-binding sites in the middle of the membrane domain and H3O+ secretion depends on a conformational change involving Lys(791) insertion into the second H3O+ site enclosed by E795, E820, and D824 that allows export of protons at a concentration of 160 mM. K+ countertransport involves binding to this site after the release of protons with retrograde displacement of Lys(791) and then K+ transfer to E343 and exit to the cytoplasm. This ATPase is the major therapeutic target in treatment of acid-related diseases and there are several known luminal inhibitors allowing analysis of the luminal vestibule. One class contains the acid-activated covalent, thiophilic proton pump inhibitors, the most effective of current acid-suppressive drugs. Their binding sites and trypsinolysis allowed identification of all ten transmembrane segments of the ATPase. In addition, various K+-competitive inhibitors of the ATPase are being developed, with the advantage of complete and rapid inhibition of acid secretion independent of pump activity and allowing further refinement of the structure of the luminal vestibule of the E-2 form of this ATPase. (C) 2011 American Physiological Society. Compr Physiol 1: 2141-2153, 2011. C1 [Shin, Jai Moo; Munson, Keith; Sachs, George] Univ Calif Los Angeles, Dept Med Physiol, Los Angeles, CA 90095 USA. [Shin, Jai Moo; Munson, Keith; Sachs, George] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Shin, JM (reprint author), Univ Calif Los Angeles, Dept Med Physiol, Los Angeles, CA 90095 USA. EM jaishin@ucla.edu FU US VA; NIH/NIDDK [DK053642, DK058333] FX This work was supported by US VA Merit Grant, NIH/NIDDK grant numbers DK053642 and DK058333. NR 110 TC 8 Z9 8 U1 1 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2040-4603 J9 COMPR PHYSIOL JI Compr. Physiol. PD OCT PY 2011 VL 1 IS 4 BP 2141 EP 2153 DI 10.1002/cphy.c110010 PG 13 WC Physiology SC Physiology GA V27SM UT WOS:000208632900018 PM 23733700 ER PT J AU Pugh, MJV Hanlon, JT Wang, CP Semla, T Burk, M Amuan, ME Lowery, A Good, CB Berlowitz, DR AF Pugh, Mary Jo V. Hanlon, Joseph T. Wang, Chen-Pin Semla, Todd Burk, Muriel Amuan, Megan E. Lowery, Ashlei Good, Chester B. Berlowitz, Dan R. TI Trends in Use of High-Risk Medications for Older Veterans: 2004 to 2006 SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE inappropriate prescribing; quality of care; aged; pharmacoepidemiology ID ELDERLY VETERANS; CLAIMS DATABASE; HEALTH; AFFAIRS; FALLS; DRUG; CARE; NITROFURANTOIN; CRITERIA; PATIENT AB OBJECTIVES: To examine the change in use of high-risk medications for the elderly (HRME), as defined by the National Committee on Quality Assurance's Healthcare Effectiveness Data and Information Set (HEDIS) quality measure (HEDIS HRME), by older outpatient veterans over a 3-year period and to identify risk factors for HEDIS HRME exposure overall and for the most commonly used drug classes. DESIGN: Longitudinal retrospective database analysis. SETTING: Outpatient clinics within the Department of Veterans Affairs (VA). PARTICIPANTS: Veterans aged 65 by October 1, 2003, and who received VA care at least once each year until September 30, 2006. MEASUREMENTS: Rates of use of HEDIS HRME overall and according to specific drug classes each year from fiscal year 2004 (FY04) to FY06. RESULTS: In a cohort of 1,567,467, high-risk medication exposure fell from 13.1% to 12.3% between FY04 and FY06 (P < .001). High-risk antihistamines (e. g., diphenhydramine), opioid analgesics (e. g., propoxyphene), skeletal muscle relaxants (e. g., cyclobenzaprine), psychotropics (e. g., long half-life benzodiazepines), endocrine (e. g., estrogen), and cardiac medications (e. g., short-acting nifedipine) had modest but statistically significant (P < .001) reductions (range -3.8% to -16.0%); nitrofurantoin demonstrated a statistically significant increase (+36.5%; P < .001). Overall HEDIS HRME exposure was more likely for men, Hispanics, those receiving more medications, those with psychiatric comorbidity, and those without prior geriatric care. Exposure was lower for individuals exempt from copayment. Similar associations were seen between ethnicity, polypharmacy, psychiatric comorbidity, access-to-care factors, and use of individual HEDIS HRME classes. CONCLUSION: HEDIS HRME drug exposure decreased slightly in an integrated healthcare system. Risk factors for exposure were not consistent across drug groups. Future studies should examine whether interventions to further reduce HEDIS HRME use improve health outcomes. J Am Geriatr Soc 59:1891-1898, 2011. C1 [Pugh, Mary Jo V.] S Texas Vet Hlth Care Syst 11C6, VERDICT REAP, Vet Evidence Based Res & Implementat Ctr, San Antonio, TX 78023 USA. [Pugh, Mary Jo V.; Wang, Chen-Pin] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Lowery, Ashlei] Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr Gerontol & Palliat Med, San Antonio, TX 78229 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Div Geriatr Med, Dept Pharm & Therapeut, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Div Geriatr Med, Pittsburgh, PA 15261 USA. [Good, Chester B.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Hanlon, Joseph T.; Good, Chester B.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Hanlon, Joseph T.; Good, Chester B.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Semla, Todd; Burk, Muriel] Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA. [Semla, Todd; Burk, Muriel] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Semla, Todd; Burk, Muriel; Berlowitz, Dan R.] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Amuan, Megan E.] Ctr Hlth Qual Outcomes & Econ Res, Dept Vet Affairs, Bedford, MA USA. [Berlowitz, Dan R.] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Pugh, MJV (reprint author), S Texas Vet Hlth Care Syst 11C6, VERDICT REAP, Vet Evidence Based Res & Implementat Ctr, 7400 Merton Minter, San Antonio, TX 78023 USA. EM maryjo.pugh2@va.gov OI Pugh, Mary Jo/0000-0003-4196-7763 FU South Texas Veterans Healthcare System/Audie L. Murphy Division; Veterans Evidence-based Research and Implementation Center; VA Health Services Research and Development Service (HSRD) [DHI-09-237, IIR-06-062, IIR 08-274, SDR-07-042, IIR-05-121, IAF-06-080, IIR-09-335, SHP 08-140, TRX 01-091]; Epilepsy Foundation; Department of Defense CDMRP [09090014]; NIH [R01-NR010828]; VA Health Services Research [IIR-06-062]; National Institute of Aging [R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056]; National Institute of Mental Health [R34 MH082682]; National Institute of Nursing Research [R01NR010135]; Agency for Healthcare Research and Quality [R01HS017695] FX The authors acknowledge and appreciate support from the South Texas Veterans Healthcare System/Audie L. Murphy Division and the Veterans Evidence-based Research and Implementation Center. The views expressed in this article are those of the authors and do not necessarily represent the views of the VA. We acknowledge the contributions of Jeffrey Tabares and Ranjani Davalath in assisting with manuscript preparation.; Dr. Pugh has received research funding from VA Health Services Research and Development Service (HSRD) DHI-09-237 (PI); VA HSRD IIR-06-062 PI, Epilepsy Foundation PI, VA HSRD PPO 09-295 PI, VA HSRD IIR 02-274 PI. Pugh as co-I: VA HSRD IIR 08-274, VA HSRD SDR-07-042, IIR-05-121, IAF-06-080, IIR-09-335, SHP 08-140, TRX 01-091 Department of Defense CDMRP 09090014, NIH R01-NR010828,; This study was supported by a VA Health Services Research grant (IIR-06-062, Dr. Pugh PI). Dr Hanlon is supported by National Institute of Aging grants (R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056), a National Institute of Mental Health grant (R34 MH082682), a National Institute of Nursing Research grant (R01NR010135), and an Agency for Healthcare Research and Quality grant (R01HS017695). NR 39 TC 14 Z9 15 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2011 VL 59 IS 10 BP 1891 EP 1898 DI 10.1111/j.1532-5415.2011.03559.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 840OE UT WOS:000296449300014 PM 21883108 ER PT J AU Pratchett, LC Daly, K Bierer, LM Yehuda, R AF Pratchett, Laura C. Daly, Kelly Bierer, Linda M. Yehuda, Rachel TI New approaches to combining pharmacotherapy and psychotherapy for posttraumatic stress disorder SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE evidence-based psychotherapy; pharmacologic augmentation of psychotherapy; pharmacotherapy; posttraumatic stress disorder; treatment ID RANDOMIZED CONTROLLED-TRIAL; EYE-MOVEMENT DESENSITIZATION; COGNITIVE-BEHAVIOR-THERAPY; REALITY EXPOSURE THERAPY; VIETNAM COMBAT VETERANS; BRIEF ECLECTIC PSYCHOTHERAPY; AFRICAN REFUGEE SETTLEMENT; PLACEBO-CONTROLLED TRIAL; SOCIAL ANXIETY DISORDER; CHILDHOOD SEXUAL-ABUSE AB Introduction: Posttraumatic stress disorder (PTSD) is a complex disorder associated with an intricate biological and psychological symptom profile and various common comorbidities. Despite an existing myriad of evidence-based and experimental treatments, PTSD is often difficult to treat. This reality necessitates a discussion of the potential of emerging treatments. Areas covered: A literature search using PubMed and PsychInfo was done using the following keywords: randomized clinical trials, treatment guidelines, pharmacotherapy and psychotherapy, all in addition to PTSD. A comprehensive treatment review establishes that early intervention approaches have not yet been found to prevent PTSD in trauma survivors. However, psychotherapy research provides substantial support for cognitive behavioral therapies and eye movement desensitization and reprocessing for chronic PTSD, and psychopharmacological approaches are myriad - although at present there is FDA approval only for sertraline and paroxetine. However, the efficacy of these treatments varies and, unfortunately, not everyone will achieve remission. Expert opinion: So far, the mental health field has tended to focus on either biological or psychological targets. We propose that maximizing treatment success may require an integrated approach that does not dichotomize biological and psychological aspects. Exciting new developments reflecting this perspective include psychopharmacologic augmentation strategies that enhance the mechanisms of psychotherapy. C1 [Pratchett, Laura C.; Bierer, Linda M.; Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Daly, Kelly] Bronx Vet Med Res Fdn, Traumat Stress Studies Div, Bronx, NY 10468 USA. [Pratchett, Laura C.; Bierer, Linda M.; Yehuda, Rachel] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. RP Pratchett, LC (reprint author), James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. EM Laura.pratchett@va.gov NR 195 TC 17 Z9 18 U1 11 U2 30 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD OCT PY 2011 VL 12 IS 15 BP 2339 EP 2354 DI 10.1517/14656566.2011.604030 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 820MC UT WOS:000294909000006 PM 21819273 ER PT J AU Spina, JR Glassman, PA Simon, B Lanto, A Lee, M Cunningham, F Good, CB AF Spina, Jeffrey R. Glassman, Peter A. Simon, Barbara Lanto, Andrew Lee, Martin Cunningham, Francesca Good, Chester B. TI Potential Safety Gaps in Order Entry and Automated Drug Alerts A Nationwide Survey of VA Physician Self-Reported Practices With Computerized Order Entry SO MEDICAL CARE LA English DT Article DE medication safety; clinical decision support systems; drug interactions; medication errors; attitude of health personnel ID CLINICAL DECISION-SUPPORT; PRIMARY-CARE; MEDICATION SAFETY; AMBULATORY-CARE AB Objective: Understanding provider perceptions of and experiences with order entry and order checks (drug alerts) in an electronic prescribing system may help improve medication safety technology. Design: Cross-sectional, national survey of Veterans Administration physicians practicing in various specialties. Measurement: Thirty-five question instrument was divided into 4 content domains. Response options included dichotomous, numeric, multiple choices, and Likert-like scales. Statistical methods included logistic regression. Results: The adjusted response rate was 1543 of 3588 (43%). Almost all providers (90%) felt that the VA electronic prescribing system, including its order checks, improved prescribing safety to some degree. Most respondents (72%) reported that they always or almost always document outside medications in a clinic note, although only 44% always or almost always entered outside medications in the non-VA medication data field. Most physicians (88%) who encountered serious allergic or adverse drug reactions reported either notifying a pharmacist or entering the information in the allergies/adverse reactions field. Generalists and physicians with higher numbers of prescriptions were more likely to enter relevant data into the electronic medical record (or notify a pharmacist, in the case of adverse reactions). In addition, 48% of providers described critical drug-drug interaction alerts as very useful; medical specialists found these less useful, whereas surgical specialists found these more useful when compared with generalists. Limitations: Survey was conducted within a single healthcare system. Conclusion: Computerized provider order entry and related order checks are perceived to improve prescribing safety; however, provider entry of some relevant information into the appropriate electronic fields may not be optimal. C1 [Spina, Jeffrey R.; Glassman, Peter A.; Simon, Barbara; Lanto, Andrew; Lee, Martin] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Spina, Jeffrey R.; Glassman, Peter A.; Lee, Martin] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Glassman, Peter A.; Simon, Barbara; Lanto, Andrew; Lee, Martin] VA HSR&D Ctr Study Healthcare Provider Behav, Hines, IL USA. [Glassman, Peter A.; Cunningham, Francesca; Good, Chester B.] VA Ctr Medicat Safety, Hines, IL USA. [Lee, Martin] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Cunningham, Francesca] VA Pharm Benefits Management Serv, Hines, IL USA. [Good, Chester B.] Pittsburgh VA Med Ctr, Pittsburgh, PA USA. RP Spina, JR (reprint author), 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Jeffrey.Spina@va.gov NR 23 TC 6 Z9 6 U1 3 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 OCT PY 2011 VL 49 IS 10 BP 904 EP 910 DI 10.1097/MLR.0b013e318222a6f5 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 821EO UT WOS:000294957900005 PM 21666510 ER PT J AU Kautz, SA Bowden, MG Clark, DJ Neptune, RR AF Kautz, Steven A. Bowden, Mark G. Clark, David J. Neptune, Richard R. TI Comparison of Motor Control Deficits During Treadmill and Overground Walking Poststroke SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE walking; stroke; motor control; treadmill; overground ID GROUND REACTION FORCES; MUSCLE SYNERGIES; GAIT PATTERN; LOCOMOTION; STROKE; SPEED; COORDINATION; HEMIPARESIS; PERFORMANCE AB Background. Force-sensing split-belt treadmills (TMs) provide an alternative to the conventional overground (OG) setting and allow new avenues for analyzing the biomechanics and motor control of walking. However, walking control may differ on a TM compared with walking OG. Objective. To compare spatiotemporal, kinematic, and EMG-based measures of motor control between TM and OG walking at self-selected and fastest comfortable speeds in persons with poststroke hemiparesis. Methods. Individuals with chronic hemiparesis (56) and similarly aged healthy individuals (17) walked over an instrumented walkway and on an instrumented split-belt TM; 16 channels of EMG recorded bilateral muscle activity, and a 12-camera motion capture system collected bilateral 3D kinematics. The authors applied a nonnegative matrix factorization (NNMF) algorithm to examine the underlying patterns of motor control. Results. Self-selected walking patterns differed on the TM versus OG in controls: speed decreased, stride length decreased, stance percentage increased, and double-support percentage increased. Poststroke, responses were similar, but cadence also decreased, and step length asymmetry increased. Kinematic patterns were similar except those associated with slower walking speeds. NNMF demonstrated similar EMG variance in the 2 environments. Conclusion. Persons, both healthy and poststroke, walk with different gait parameters on the TM. Although measures of motor control were mostly similar between the 2 environments, the TM induced step length asymmetry in 30% of participants (60% of whom took longer paretic steps). TM walking, therefore, is a valid method for detecting motor control deficits. C1 [Kautz, Steven A.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Kautz, Steven A.; Bowden, Mark G.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Clark, David J.] Malcom Randall VA Med Ctr, Brain Rehabil Res Ctr, Gainesville, FL USA. [Neptune, Richard R.] Univ Texas Austin, Austin, TX 78712 USA. RP Kautz, SA (reprint author), Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. EM kautz@musc.edu RI Clark, David/A-4916-2013 OI Kautz, Steven/0000-0003-3151-8235 FU NIH [R01 HD46820]; VA Rehabilitation R&D Center of Excellence [F2182C]; Office of Research and Development, Rehabilitation R & D Service, Department of Veterans Affairs (VA); Malcom Randall VA Medical Center, Gainesville, FL FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by NIH R01 HD46820 and VA Rehabilitation R&D Center of Excellence Grant F2182C. This material is the result of work supported in part by the Office of Research and Development, Rehabilitation R & D Service, Department of Veterans Affairs (VA), and the Malcom Randall VA Medical Center, Gainesville, FL. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, National Institute of Child Health and Human Development (NICHHD), or VA. NR 30 TC 33 Z9 34 U1 1 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD OCT PY 2011 VL 25 IS 8 BP 756 EP 764 DI 10.1177/1545968311407515 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 820ID UT WOS:000294898000008 PM 21636831 ER PT J AU Sharpless, BA Barber, JP AF Sharpless, Brian A. Barber, Jacques P. TI Lifetime prevalence rates of sleep paralysis: A systematic review SO SLEEP MEDICINE REVIEWS LA English DT Review DE Sleep paralysis; Isolated sleep paralysis; Anxiety; Fear; Parasomnia; Prevalence ID CHILDHOOD SEXUAL-ABUSE; GENERAL-POPULATION; MEDICAL-STUDENTS; PANIC DISORDER; COLLEGE-STUDENTS; HALLUCINATIONS; SYMPTOMATOLOGY; KANASHIBARI; OUTPATIENTS; FREQUENCY AB Objective: To determine lifetime prevalence rates of sleep paralysis. Data sources: Keyword term searches using "sleep paralysis", "isolated sleep paralysis", or "parasomnia not otherwise specified" were conducted using MEDLINE (1950-present) and PsychINFO (1872-present). English and Spanish language abstracts were reviewed, as were reference lists of identified articles. Study selection: Thirty five studies that reported lifetime sleep paralysis rates and described both the assessment procedures and sample utilized were selected. Data extraction: Weighted percentages were calculated for each study and, when possible, for each reported subsample. Data synthesis: Aggregating across studies (total N = 36,533), 7.6% of the general population, 28.3% of students, and 31.9% of psychiatric patients experienced at least one episode of sleep paralysis. Of the psychiatric patients with panic disorder, 34.6% reported lifetime sleep paralysis. Results also suggested that minorities experience lifetime sleep paralysis at higher rates than Caucasians. Conclusions: Sleep paralysis is relatively common in the general population and more frequent in students and psychiatric patients. Given these prevalence rates, sleep paralysis should be assessed more regularly and uniformly in order to determine its impact on individual functioning and better articulate its relation to psychiatric and other medical conditions. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Sharpless, Brian A.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. [Barber, Jacques P.] Univ Penn, Ctr Psychotherapy Res, Dept Psychiat, Philadelphia, PA 19104 USA. [Barber, Jacques P.] Univ Philadelphia, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Sharpless, BA (reprint author), Penn State Univ, Dept Psychol, 317 Moore Bldg, University Pk, PA 16802 USA. EM bas171@psu.edu; barberj@mail.med.upenn.edu FU NIMH [R01 MH 070664] FX We would like to thank the authors who responded to our emails with additional clarifications on their published studies as well as the anonymous reviewers. This work was supported in part by a grant (NIMH R01 MH 070664) held by Jacques P. Barber. NR 49 TC 22 Z9 23 U1 5 U2 30 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1087-0792 J9 SLEEP MED REV JI Sleep Med. Rev. PD OCT PY 2011 VL 15 IS 5 BP 311 EP 315 DI 10.1016/j.smrv.2011.01.007 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 820YL UT WOS:000294941900005 PM 21571556 ER PT J AU Yao, JK Reddy, R AF Yao, Jeffrey K. Reddy, Ravinder TI Oxidative Stress in Schizophrenia: Pathogenetic and Therapeutic Implications SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Editorial Material ID SYSTEM; BRAIN; ABNORMALITIES AB Over a century, a wide-ranging variety of pathophysiological models and causal hypotheses have been conceptualized for schizophrenia. One among these is the role for free radical-mediated pathology in schizophrenia, indicating impaired antioxidant defense system (AODS) and presence of oxidative stress in patients with schizophrenia. For the past two decades, the whole investigative domain of AODS and oxidative stress has broadened to include the wider AODS components, direct central nervous system assays of AODS, chemical imaging studies, proteomics, genetics of AODS, and, of importance to sufferers of schizophrenia, antioxidant therapeutics. These are some of the perspectives that are reviewed by several articles in this Forum. Overall, there has been growing recognition of the importance of oxidative stress in the pathophysiology of schizophrenia and in treatment-related side effects. The totality of the evidence from biochemistry, metabolomics, proteomics, genetics, and in vivo brain imaging points to the presence of multifarious abnormalities in the AODS and redox signaling in schizophrenia. Antioxid. Redox Signal. 15, 1999-2002. C1 [Yao, Jeffrey K.; Reddy, Ravinder] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA 15206 USA. [Yao, Jeffrey K.; Reddy, Ravinder] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Med Res Serv, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM jkyao@pitt.edu FU NIMH NIH HHS [MH58141] NR 33 TC 38 Z9 39 U1 1 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD OCT PY 2011 VL 15 IS 7 BP 1999 EP 2002 DI 10.1089/ars.2010.3646 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 818QY UT WOS:000294770900016 PM 21194354 ER PT J AU Yao, JK Keshavan, MS AF Yao, Jeffrey K. Keshavan, Matcheri S. TI Antioxidants, Redox Signaling, and Pathophysiology in Schizophrenia: An Integrative View SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID NITRIC-OXIDE SYNTHASE; POLYUNSATURATED FATTY-ACIDS; MAGNETIC-RESONANCE-SPECTROSCOPY; SERUM URIC-ACID; MEMBRANE PHOSPHOLIPID-METABOLISM; PERFORMANCE LIQUID-CHROMATOGRAPHY; SUPEROXIDE-DISMUTASE ACTIVITY; LIPID-PEROXIDATION PRODUCTS; NEVER-MEDICATED 1ST-EPISODE; MULTIPLE-SCLEROSIS PATIENTS AB Schizophrenia (SZ) is a brain disorder that has been intensively studied for over a century; yet, its etiology and multifactorial pathophysiology remain a puzzle. However, significant advances have been made in identifying numerous abnormalities in key biochemical systems. One among these is the antioxidant defense system (AODS) and redox signaling. This review summarizes the findings to date in human studies. The evidence can be broadly clustered into three major themes: perturbations in AODS, relationships between AODS alterations and other systems (i.e., membrane structure, immune function, and neurotransmission), and clinical implications. These domains of AODS have been examined in samples from both the central nervous system and peripheral tissues. Findings in patients with SZ include decreased nonenzymatic antioxidants, increased lipid peroxides and nitric oxides, and homeostatic imbalance of purine catabolism. Reductions of plasma antioxidant capacity are seen in patients with chronic illness as well as early in the course of SZ. Notably, these data indicate that many AODS alterations are independent of treatment effects. Moreover, there is burgeoning evidence indicating a link among oxidative stress, membrane defects, immune dysfunction, and multineurotransmitter pathologies in SZ. Finally, the body of evidence reviewed herein provides a theoretical rationale for the development of novel treatment approaches. Antioxid. Redox Signal. 15, 2011-2035. C1 [Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. [Yao, Jeffrey K.; Keshavan, Matcheri S.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Keshavan, Matcheri S.] Harvard Univ, Boston, MA 02115 USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst 151U H, Med Res Serv, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM jkyao@pitt.edu FU Department of Veterans Affairs; Veterans Health Administration; Office of Research and Development; Biomedical Laboratory RD; VA Pittsburgh Healthcare System; National Institute of Health [MH58141, MH45203] FX This material is based upon work supported in part by the grants from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory R&D (Merit Reviews and Senior Research Career Scientist Award), VA Pittsburgh Healthcare System, and National Institute of Health [MH58141 (J.K.Y.), and MH45203 (M.S.K.)]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. The contents of this article do not represent the views of the Department of Veterans Affairs or the U.S. Government. NR 308 TC 102 Z9 104 U1 3 U2 23 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD OCT PY 2011 VL 15 IS 7 BP 2011 EP 2035 DI 10.1089/ars.2010.3603 PG 25 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 818QY UT WOS:000294770900018 PM 21126177 ER PT J AU Reddy, R Reddy, R AF Reddy, Ravinder Reddy, Rajiv TI Antioxidant Therapeutics for Schizophrenia SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID VITAMIN-E TREATMENT; POLYUNSATURATED FATTY-ACIDS; TERM TARDIVE-DYSKINESIA; LIPID-PEROXIDATION; OXIDATIVE STRESS; ATYPICAL ANTIPSYCHOTICS; OPEN-LABEL; SUPPLEMENTATION; OMEGA-3-FATTY-ACIDS; METAANALYSIS AB Pharmaceutical treatment for millions worldwide who have schizophrenia is limited to a handful of antipsychotics. Despite the proven efficacy of these drugs, the overall outcome for schizophrenia remains suboptimal. Thus, alternative treatment options are urgently needed. One possible approach may be antioxidant therapy. The extant evidence for the role of oxidative stress in the pathophysiology of schizophrenia offers a hypothesis-derived therapeutic approach in the form of antioxidants. Vitamins C and E, for example, are suitable for human clinical trials because they are readily available, inexpensive, and relatively safe. Research into the therapeutic use of antioxidants in schizophrenia can be grouped into two main clusters: for psychopathology and for side effects. Of these studies, some have been carefully conducted, but majority are open label. Use of antioxidants for treatment-related side effects has been more extensively investigated. The totality of the evidence to date suggests that specific antioxidants, such as N-acetyl cysteine, may offer tangible benefits for the clinical syndrome of schizophrenia, and vitamin E may offer salutary effects on glycemic effects of antipsychotics. However, a great deal of fundamental clinical research remains to be done before antioxidants can be routinely used therapeutically for schizophrenia and treatment-related complications. Antioxid. Redox Signal. 15, 2047-2055. C1 [Reddy, Ravinder] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Reddy, Ravinder] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Reddy, Rajiv] Univ Toledo, Sch Med, Toledo, OH 43606 USA. RP Reddy, R (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM reddyr@upmc.edu NR 55 TC 17 Z9 17 U1 1 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD OCT PY 2011 VL 15 IS 7 BP 2047 EP + DI 10.1089/ars.2010.3571 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 818QY UT WOS:000294770900020 PM 20977337 ER PT J AU Wang, YN Lee, K Pai, S Ledoux, WR AF Wang, Y. N. Lee, K. Pai, S. Ledoux, W. R. TI Histomorphometric comparison after fixation with formaldehyde or glyoxal SO BIOTECHNIC & HISTOCHEMISTRY LA English DT Article DE formaldehyde; glyoxal; heel pad; plantar soft tissue; stereology; structural properties ID STEREOLOGICAL METHODS; VERTICAL SECTIONS; TISSUE-SECTIONS; SURFACE-AREA; SPECIMENS; THICKNESS; HISTOLOGY; BIOLOGY; SKIN AB Formaldehyde has long been the fixative of choice for histological examination of tissue. The use of alternatives to formaldehyde has grown, however, owing to the serious hazards associated with its use. Companies have striven to maintain the morphological characteristics of formaldehyde-fixed tissue when developing alternatives. Glyoxal-based fixatives now are among the most popular formaldehyde alternatives. Although there are many studies that compare staining quality and immunoreactivity, there have been no studies that quantify possible structural differences. Histomorphometric analysis commonly is used to evaluate diseased tissue. We compared fixation with formaldehyde and glyoxal with regard to the histomorphological properties of plantar foot tissue using a combination of stereological methods and quantitative morphology. We measured skin thickness, interdigitation index, elastic septa thickness, and adipocyte area and diameter. No significant differences were observed between formaldehyde and glyoxal fixation for any feature measured. The glyoxal-based fixative used therefore is a suitable fixative for structural evaluation of plantar soft tissue. Measurements obtained from the glyoxal-fixed tissue can be combined with data obtained from formalin-fixed for analysis. C1 [Wang, Y. N.; Lee, K.; Pai, S.; Ledoux, W. R.] Univ Washington, VA Puget Sound Hlth Care Syst, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Dept Vet Affairs, Seattle, WA 98195 USA. [Wang, Y. N.] Univ Washington, Appl Phys Lab, Seattle, WA 98195 USA. [Pai, S.; Ledoux, W. R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Ledoux, W. R.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), 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 [R01DK75633-03, P30DK017047]; Department of Veterans Affairs, RRD Service [A4843C] FX This study was supported by NIH grants R01DK75633-03 and P30DK017047 and the Department of Veterans Affairs, RR&D Service grant A4843C. NR 21 TC 5 Z9 6 U1 0 U2 9 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1052-0295 J9 BIOTECH HISTOCHEM JI Biotech. Histochem. PD OCT PY 2011 VL 86 IS 5 BP 359 EP 365 DI 10.3109/10520295.2010.520275 PG 7 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA 818UT UT WOS:000294782000009 PM 20854226 ER PT J AU Eschler, DC Hasham, A Tomer, Y AF Eschler, Deirdre Cocks Hasham, Alia Tomer, Yaron TI Cutting Edge: The Etiology of Autoimmune Thyroid Diseases SO CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY LA English DT Review DE Thyroid genetics; Autoimmune thyroid disorders epigenetics ID SINGLE-NUCLEOTIDE POLYMORPHISM; CHRONIC HEPATITIS-C; II PEPTIDE-BINDING; GRAVES-DISEASE; INTERFERON-ALPHA; GENETIC SUSCEPTIBILITY; CD40 GENE; THYROGLOBULIN; AMIODARONE; EPIDEMIOLOGY AB Significant progress has been made in our understanding of the mechanisms leading to autoimmune thyroid diseases (AITD). For the first time, we are beginning to unravel these mechanisms at the molecular level. AITD, including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are common autoimmune diseases affecting the thyroid. They have a complex etiology that involves genetic and environmental influences. Seven genes have been shown to contribute to the etiology of AITD. The first AITD gene discovered, HLA-DR3, is associated with both GD and HT. More recently, this association was dissected at the molecular level when it was shown that substitution of the neutral amino acids Ala or Gln with arginine at position beta 74 in the HLA-DR peptide binding pocket is the specific sequence change causing AITD. Non-MHC genes that confer susceptibility to AITD can be classified into two groups: (1) immune-regulatory genes (e.g., CD40, CTLA-4, and PTPN22); (2) thyroid-specific genes-thyroglobulin and TSH receptor genes. These genes interact with environmental factors, such as infection, likely through epigenetic mechanisms to trigger disease. In this review, we summarize the latest findings on disease susceptibility and modulation by environmental factors. C1 [Eschler, Deirdre Cocks; Hasham, Alia; Tomer, Yaron] Mt Sinai Med Ctr, Dept Med, Div Endocrinol, New York, NY 10029 USA. [Tomer, Yaron] James J Peters VA Med Ctr, New York, NY 10029 USA. RP Tomer, Y (reprint author), Mt Sinai Med Ctr, Dept Med, Div Endocrinol, 1 Gustave L Levy Pl,Box 1118, New York, NY 10029 USA. EM Yaron.Tomer@mssm.edu FU NIDDK [DK061659, DK067555, DK073681] FX This work was supported in part by grants DK061659, DK067555, and DK073681 from NIDDK. NR 63 TC 30 Z9 32 U1 2 U2 27 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1080-0549 J9 CLIN REV ALLERG IMMU JI Clin. Rev. Allergy Immunol. PD OCT PY 2011 VL 41 IS 2 BP 190 EP 197 DI 10.1007/s12016-010-8245-8 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 819KB UT WOS:000294822700008 PM 21234711 ER PT J AU Martinez, HG Quinones, MP Jimenez, F Estrada, CA Clark, K Muscogiuri, G Sorice, G Musi, N Reddick, RL Ahuja, SS AF Martinez, H. G. Quinones, M. P. Jimenez, F. Estrada, C. A. Clark, K. Muscogiuri, G. Sorice, G. Musi, N. Reddick, R. L. Ahuja, S. S. TI Critical role of chemokine (C-C motif) receptor 2 (CCR2) in the KKAy (+) Apoe (-/-) mouse model of the metabolic syndrome SO DIABETOLOGIA LA English DT Article DE Animal-mouse; Basic science; Cardiac complications; Experimental immunology; KO mice; Metabolic syndrome; Nephropathy ID GLYCOGEN-SYNTHASE KINASE-3; TYPE-2 DIABETES-MELLITUS; INSULIN-RESISTANCE; APOLIPOPROTEIN-E; HEPATIC STEATOSIS; SKELETAL-MUSCLE; DENDRITIC CELLS; ADIPOSE-TISSUE; KNOCKOUT MICE; HIGH-FAT AB Chemokines and their receptors such as chemokine (C-C motif) receptor 2 (CCR2) may contribute to the pathogenesis of the metabolic syndrome via their effects on inflammatory monocytes. Increased accumulation of CCR2-driven inflammatory monocytes in epididymal fat pads is thought to favour the development of insulin resistance. Ultimately, the resulting hyperglycaemia and dyslipidaemia contribute to development of the metabolic syndrome complications such as cardiovascular disease and diabetic nephropathy. Our goal was to elucidate the role of CCR2 and inflammatory monocytes in a mouse model that resembles the human metabolic syndrome. We generated a model of the metabolic syndrome by backcrossing KKAy (+) with Apoe (-/-) mice (KKAy (+) Apoe (-/-) ) and studied the role of CCR2 in this model system. KKAy (+) Apoe (-/-) mice were characterised by the presence of obesity, insulin resistance, dyslipidaemia and increased systemic inflammation. This model also manifested two complications of the metabolic syndrome: atherosclerosis and diabetic nephropathy. Inactivation of Ccr2 in KKAy (+) Apoe (-/-) mice protected against the metabolic syndrome, as well as atherosclerosis and diabetic nephropathy. This protective phenotype was associated with a reduced number of inflammatory monocytes in the liver and muscle, but not in the epididymal fat pads; circulating levels of adipokines such as leptin, resistin and adiponectin were also not reduced. Interestingly, the proportion of inflammatory monocytes in the liver, pancreas and muscle, but not in the epididymal fat pads, correlated significantly with peripheral glucose levels. CCR2-driven inflammatory monocyte accumulation in the liver and muscle may be a critical pathogenic factor in the development of the metabolic syndrome. C1 [Martinez, H. G.; Jimenez, F.; Estrada, C. A.; Clark, K.; Muscogiuri, G.; Sorice, G.; Musi, N.; Ahuja, S. S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med MC 7870, San Antonio, TX 78229 USA. [Martinez, H. G.; Jimenez, F.; Ahuja, S. S.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Quinones, M. P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Reddick, R. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. RP Ahuja, SS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med MC 7870, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM ahuja@uthscsa.edu FU Fraternal Order of Eagles; Veterans' Administration Merit Award; NIH [RO1 AR 052755] FX We thank Y. Patel (Department of Pathology, UTHSCSA) for help with HPLC measurement of creatinine. This work was supported by grants from Fraternal Order of Eagles, a Veterans' Administration Merit Award, and NIH RO1 AR 052755 to S. S. Ahuja. NR 40 TC 8 Z9 8 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 2011 VL 54 IS 10 BP 2660 EP 2668 DI 10.1007/s00125-011-2248-8 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 817OF UT WOS:000294683000022 PM 21779871 ER PT J AU Halpern, SD Kohn, R Dornbrand-Lo, A Metkus, T Asch, DA Volpp, KG AF Halpern, Scott D. Kohn, Rachel Dornbrand-Lo, Aaron Metkus, Thomas Asch, David A. Volpp, Kevin G. TI Lottery-Based versus Fixed Incentives to Increase Clinicians' Response to Surveys SO HEALTH SERVICES RESEARCH LA English DT Article DE Incentives; response rate; surveys; lottery; behavioral economics ID RANDOMIZED-TRIAL; MAIL SURVEYS; PHYSICIAN RESPONSE; COST-EFFECTIVENESS; RATES; CASH; QUESTIONNAIRES; 5-DOLLAR; PAY AB Objective. To compare the effects of lottery-based and fixed incentives on clinicians' response to surveys. Data Sources. Three randomized trials with fixed payments and actuarially equivalent lotteries. Study Design. Trial 1 compared a low-probability/high-payout lottery, a high-probability/low-payout lottery, and no incentive. Trial 2 compared a moderate-probability/moderate-payout lottery with an unconditional fixed payment (payment sent with questionnaire). Trial 3 compared a moderate-probability/moderate-payout lottery with a conditional fixed payment (payment promised following response). Principal Findings. Neither the low-probability nor high-probability lotteries improved response compared with no incentive. Unconditional fixed payments produced significantly greater response than actuarially equivalent lotteries, but conditional fixed payments did not. Conclusions. Lottery-based incentives do not improve clinicians' response rates compared with no incentives, and they are inferior to unconditional fixed payments. C1 [Halpern, Scott D.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Halpern, Scott D.; Asch, David A.; Volpp, Kevin G.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Halpern, Scott D.; Dornbrand-Lo, Aaron; Asch, David A.; Volpp, Kevin G.] Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent, Philadelphia, PA 19104 USA. [Halpern, Scott D.; Kohn, Rachel; Asch, David A.] Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. [Metkus, Thomas] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Asch, David A.; Volpp, Kevin G.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Halpern, SD (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 723 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM shalpern@exchange.upenn.edu OI Asch, David/0000-0002-7970-286X FU Greenwall Foundation; Leonard Davis Institute of Health Economics Center for Health Incentives; University of Pennsylvania FX Incentives used in this study came from funds provided by a Greenwall Foundation Faculty Scholar Award in Bioethics (SDH), the Leonard Davis Institute of Health Economics Center for Health Incentives (KGV), and the University of Pennsylvania Medical Education Research Fund (SDH). None of these sponsors were involved in the preparation of the manuscript or in the decision to submit the manuscript for publication. NR 27 TC 13 Z9 13 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2011 VL 46 IS 5 BP 1663 EP 1674 DI 10.1111/j.1475-6773.2011.01264.x PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 818GN UT WOS:000294739800018 PM 21492159 ER PT J AU Costanza, A Weber, K Gandy, S Bouras, C Hof, PR Giannakopoulos, P Canuto, A AF Costanza, A. Weber, K. Gandy, S. Bouras, C. Hof, P. R. Giannakopoulos, P. Canuto, A. TI Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Review DE Alzheimer's disease; boxing; chronic traumatic encephalopathy; contact sports; frontotemporal dementia; traumatic brain injuries ID AMYOTROPHIC-LATERAL-SCLEROSIS; BETA-AMYLOID PROTEIN; NEUROFIBRILLARY TANGLE DISTRIBUTION; REPETITIVE HEAD-INJURY; BRAIN-INJURY; ALZHEIMERS-DISEASE; DEMENTIA-PUGILISTICA; PARKINSONISM-DEMENTIA; PROFESSIONAL BOXERS; COGNITIVE IMPAIRMENT AB Professional boxers and other contact sport athletes are exposed to repetitive brain trauma that may affect motor functions, cognitive performance, emotional regulation and social awareness. The term of chronic traumatic encephalopathy (CTE) was recently introduced to regroup a wide spectrum of symptoms such as cerebellar, pyramidal and extrapyramidal syndromes, impairments in orientation, memory, language, attention, information processing and frontal executive functions, as well as personality changes and behavioural and psychiatric symptoms. Magnetic resonance imaging usually reveals hippocampal and vermis atrophy, a cavum septum pellucidum, signs of diffuse axonal injury, pituitary gland atrophy, dilated perivascular spaces and periventricular white matter disease. Given the partial overlapping of the clinical expression, epidemiology and pathogenesis of CTE and Alzheimer's disease (AD), as well as the close association between traumatic brain injuries (TBIs) and neurofibrillary tangle formation, a mixed pathology promoted by pathogenetic cascades resulting in either CTE or AD has been postulated. Molecular studies suggested that TBIs increase the neurotoxicity of the TAR DNA-binding protein 43 (TDP-43) that is a key pathological marker of ubiquitin-positive forms of frontotemporal dementia (FTLD-TDP) associated or not with motor neurone disease/amyotrophic lateral sclerosis (ALS). Similar patterns of immunoreactivity for TDP-43 in CTE, FTLD-TDP and ALS as well as epidemiological correlations support the presence of common pathogenetic mechanisms. The present review provides a critical update of the evolution of the concept of CTE with reference to its neuropathological definition together with an in-depth discussion of the differential diagnosis between this entity, AD and frontotemporal dementia. C1 [Giannakopoulos, P.] Univ Hosp, Dept Psychiat, CH-1225 Geneva, Switzerland. [Giannakopoulos, P.] Univ Geneva, Fac Med, CH-1225 Geneva, Switzerland. [Costanza, A.; Weber, K.; Bouras, C.; Canuto, A.] Univ Geneva, Sch Med, Dept Psychiat, CH-1225 Geneva, Switzerland. [Giannakopoulos, P.] Hosp CHUV, Div Old Age Psychiat, Dept Psychiat, Lausanne, Switzerland. [Gandy, S.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Gandy, S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Gandy, S.; Hof, P. R.] Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY USA. [Gandy, S.] James J Peters VA Med Ctr, Bronx, NY USA. [Hof, P. R.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. RP Giannakopoulos, P (reprint author), Univ Hosp, Dept Psychiat, CH-1225 Geneva, Switzerland. EM panteleimon.giannakopoulos@unige.ch FU NIH [AG02219, AG05138] FX We thank all the technical staff members of the Division of Neuropsychiatry of the University of Geneva Hospitals for expert assistance. This work was supported in part by NIH grants AG02219 and AG05138 (P.R.H., S.G.). NR 151 TC 45 Z9 45 U1 1 U2 26 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 OCT PY 2011 VL 37 IS 6 BP 570 EP 584 DI 10.1111/j.1365-2990.2011.01186.x PG 15 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 819KZ UT WOS:000294825300001 PM 21696410 ER PT J AU Lopez-Olivo, MA Landon, GC Siff, SJ Edelstein, D Pak, C Kallen, MA Stanley, M Zhang, H Robinson, KC Suarez-Almazor, ME AF Lopez-Olivo, Maria A. Landon, Glenn C. Siff, Sherwin J. Edelstein, David Pak, Chong Kallen, Michael A. Stanley, Melinda Zhang, Hong Robinson, Kausha C. Suarez-Almazor, Maria E. TI Psychosocial determinants of outcomes in knee replacement SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID QUALITY-OF-LIFE; TOTAL JOINT ARTHROPLASTY; SHORT-TERM RECOVERY; TOTAL HIP; FUNCTIONAL OUTCOMES; SELF-EFFICACY; SURGERY; OSTEOARTHRITIS; PAIN; POPULATION AB Objective To identify potential psychosocial and educational barriers to clinical success following knee replacement. Patients and Methods The authors evaluated 241 patients undergoing total knee replacement, preoperatively and 6 months after surgery. Outcomes included the Western Ontario McMaster (WOMAC) scale and the Knee Society rating system (KSRS). Independent variables included: the medical outcome study-social support scale; depression, anxiety and stress scale; brief COPE inventory; health locus of control; arthritis self-efficacy scale and the life orientation test-revised. Multiple regression models evaluated associations of baseline demographic and psychosocial variables with outcomes at 6 months, controlling for body mass index, comorbidities and baseline outcome scores. Results Patients' mean age was 65 +/- 9 years; 65% were women. Most patients improved outcomes after surgery. Several psychosocial variables were associated with outcomes. Regression analyses indicated lower education, less tangible support, depression, less problem-solving coping, more dysfunctional coping, lower internal locus of control were associated with worse WOMAC scores (R 2 contribution of psychosocial variables for pain 0.07; for function, 0.14). Older age, lower education, depression and less problem-solving coping were associated with poorer total KSRS scores (R 2 contribution of psychosocial variables to total KSRS model 0.09). Psychosocial variables as a set contributed from 25% to 74% of total explained variance across the models tested. Conclusion Patients' level of education, tangible support, depression, problem-solving coping, dysfunctional coping and internal locus of control were associated with pain and functional outcomes after knee replacement. The findings suggest that, in addition to medical management, perioperative psychosocial evaluation and intervention are crucial in enhancing knee replacement outcomes. C1 [Suarez-Almazor, Maria E.] Univ Texas MD Anderson Canc Ctr, Unit 1467, Houston, TX 77030 USA. [Landon, Glenn C.; Siff, Sherwin J.; Edelstein, David] St Lukes Episcopal Hlth Syst, Houston, TX USA. [Stanley, Melinda] Dept Vet Affairs Med Ctr, Houston VA HSR&D Ctr Excellence, Hlth Serv Res & Dev Serv, Houston, TX USA. [Stanley, Melinda] Baylor Coll Med, Houston, TX 77030 USA. [Stanley, Melinda] VA S Cent Mental Illness Res, Educ & Clin Ctr, N Little Rock, AR USA. RP Suarez-Almazor, ME (reprint author), Univ Texas MD Anderson Canc Ctr, Unit 1467, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM msalmazor@mdanderson.org FU National Institute for Arthritis, Musculoskeletal and Skin Disorders (NIAMS) [R01 AR48662]; Agency for Healthcare Research and Quality; VA HSR&D Houston Center of Excellence [HFP-90-020] FX This study was supported by a grant from the National Institute for Arthritis, Musculoskeletal and Skin Disorders (NIAMS; R01 AR48662). MES-A is the recipient of a K24 career award from the National Institute for Musculoskeletal and Skin Disorders. She is also the Director of the Houston Center for Education and Research on Therapeutics, funded by the Agency for Healthcare Research and Quality. It was also partly supported by the VA HSR&D Houston Center of Excellence (HFP-90-020). The views expressed are those of the authors and do not necessarily reflect those of the Department of Veterans Affairs/Baylor College of Medicine. MES-A has received honoraria from Zimmer as a speaker at the 2010 Summit on Musculoskeletal Health Disparities. NR 47 TC 48 Z9 48 U1 1 U2 16 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD OCT PY 2011 VL 70 IS 10 BP 1775 EP 1781 DI 10.1136/ard.2010.146423 PG 7 WC Rheumatology SC Rheumatology GA 814XX UT WOS:000294491600013 PM 21791452 ER PT J AU Spain, R Bourdette, D AF Spain, Rebecca Bourdette, Dennis TI The Radiologically Isolated Syndrome: Look (Again) Before You Treat SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Multiple sclerosis/diagnosis; Multiple sclerosis/therapy; Magnetic resonance imaging; Incidental findings; Brain/pathology; Disease progression; Radiologically isolated syndrome ID UNSUSPECTED MULTIPLE-SCLEROSIS; CLINICALLY ISOLATED SYNDROMES; DIAGNOSTIC-CRITERIA; FOLLOW-UP; DEMYELINATING LESIONS; INTERNATIONAL PANEL; PREDICT CONVERSION; MRI CRITERIA; DEFINITE; MS AB The advent and wide use of magnetic resonance brain imaging has led to in the unexpected detection of lesions that appear typical of multiple sclerosis (MS) in otherwise asymptomatic patients. Several cohorts of patients with the "radiologically isolated syndrome (RIS)" have been studied mainly retrospectively, and a proportion of them do go on to have clinical symptoms of MS. This has led to the not infrequent clinical conundrum of whether or not to treat patients with MRI lesions suggestive of MS, given the knowledge that MS disease-modifying therapies work best when given early in the disease course. However, the decision to proactively treat patients with RIS is countered by the increasing risks associated with MS disease-modifying therapies as well as the uncertain prognostic outcome of RIS. This review will highlight what is and is not known about the long-term outcomes of RIS and present recommendations for clinicians when faced with this challenging situation. C1 [Spain, Rebecca] Portland VA Med Ctr, Neurol Serv, Portland, OR 97239 USA. [Spain, Rebecca; Bourdette, Dennis] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. RP Spain, R (reprint author), Portland VA Med Ctr, Neurol Serv, Mail Code CR120,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM spainr@ohsu.edu FU Department of Veterans Affairs Rehabilitation Research & Development Service FX We thank Bronwyn Hamilton, MD, for sharing information about the prevalence of RIS among patients undergoing MRI for headache at Oregon Health & Science University. Dr. Spain has a Career Development Award from the Department of Veterans Affairs Rehabilitation Research & Development Service. NR 46 TC 10 Z9 12 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 EI 1534-6293 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD OCT PY 2011 VL 11 IS 5 BP 498 EP 506 DI 10.1007/s11910-011-0213-z PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 814PH UT WOS:000294468700006 PM 21748263 ER PT J AU Cameron, MH Wagner, JM AF Cameron, Michelle H. Wagner, Joanne M. TI Gait Abnormalities in Multiple Sclerosis: Pathogenesis, Evaluation, and Advances in Treatment SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE 4-Aminopyridine; Accidental falls; Botulinum toxin; Electric stimulation; Gait; Multiple sclerosis; Rehabilitation; Gait abnormalities ID FUNCTIONAL ELECTRICAL-STIMULATION; LEG CYCLING EXERCISE; WALKING PERFORMANCE; RANDOMIZED-TRIAL; 6-MINUTE WALK; DOUBLE-BLIND; SPASTICITY; PEOPLE; COMPOSITE; CAPACITY AB Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by episodic decline in various neurologic functions. Gait dysfunction in MS is distinguished by decreased gait speed, walking endurance, step length, cadence and joint motion, as well as increased metabolic cost of walking and increased variability of gait. Standardized clinical, timed, and patient-based measures can identify MS patients with gait dysfunction, and observational gait analysis, instrumented walkways, or three-dimensional gait analysis can help determine which problem underlies their gait dysfunction to help direct effective treatment. Exercise may ameliorate all types of gait dysfunction. In addition, gait dysfunction due to weakness may be alleviated by orthoses or functional electrical stimulation; gait dysfunction due to spasticity may be relieved by oral, intrathecal, or intramuscular medications. Assistive devices and balance training may reduce gait dysfunction from imbalance, and dalfampridine may accelerate gait in people with MS who walk slowly. C1 [Cameron, Michelle H.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Cameron, Michelle H.] Portland VA Med Ctr, Portland, OR USA. [Wagner, Joanne M.] St Louis Univ, Dept Phys Therapy & Athlet Training, St Louis, MO 63104 USA. RP Cameron, MH (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,CR120, Portland, OR 97239 USA. EM cameromi@ohsu.edu; jwagne34@slu.edu FU Acorda; Rehabilitation Research & Development Service, Department of Veterans Affairs FX M.H. Cameron: has been a consultant for Innovative Neurotronics; has received grant support from Acorda; and has received a career development award from the Rehabilitation Research & Development Service, Department of Veterans Affairs; J.M. Wagner: none. NR 50 TC 31 Z9 31 U1 2 U2 16 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 OCT PY 2011 VL 11 IS 5 BP 507 EP 515 DI 10.1007/s11910-011-0214-y PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 814PH UT WOS:000294468700007 PM 21779953 ER PT J AU Milanesi, A Brent, GA AF Milanesi, Anna Brent, Gregory A. TI Management of hypothyroidism in pregnancy SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE hypothyroidism; pregnancy; thyroxine therapy ID MATERNAL THYROID-FUNCTION; IN-VITRO FERTILIZATION; SUBCLINICAL HYPOTHYROIDISM; SELENIUM SUPPLEMENTATION; LEVOTHYROXINE TREATMENT; IODINE DEFICIENCY; AUTOIMMUNE-THYROIDITIS; HORMONE CONCENTRATIONS; STIMULATING HORMONE; REFERENCE INTERVALS AB Purpose of review Examine recent studies on the assessment of thyroid status in pregnancy, approach to thyroid testing, the spectrum of hypothyroidism in pregnancy, and strategies for thyroid replacement in women with known hypothyroidism. Recent findings Trimester-specific references range for thyroid-stimulating hormone (TSH) and free thyroxine in pregnancy must take into account iodine and thyroid autoantibody status, race, BMI, as well as other factors. Thyroid testing of only those pregnant women at increased risk for thyroid disease, case finding, will miss 30-80% of women with thyroid disease. Subclinical hypothyroidism is associated with an increasing number of adverse effects including infertility, miscarriage, preterm delivery, and breech presentation at birth. Many pregnant women with known hypothyroidism have an out-of-range TSH at the time of confirmed pregnancy. A variety of strategies are effective at keeping serum TSH normal during pregnancy including preconception increase in thyroxine, increase in thyroxine dose at the time pregnancy is confirmed, or making adjustments based on serum TSH monitoring. Summary Evaluation of thyroid status in pregnancy requires an understanding of pregnancy-associated changes in thyroid function tests and how they vary by trimester. The spectrum of hypothyroidism in pregnancy includes isolated thyroid peroxidase antibody positivity, isolated hypothyroxinemia, subclinical and overt hypothyroidism. These patterns, in some situations, may be related to iodine status, selenium status, or underlying thyroid disease. There are a variety of approaches to management of thyroxine replacement in known hypothyroid women at the time of pregnancy that are all effective at maintaining a normal range during pregnancy. C1 [Milanesi, Anna; Brent, Gregory A.] VA Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, Dept Med, Los Angeles, CA USA. [Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. RP Brent, GA (reprint author), 111 VA Greater Los Angeles Healthcare Syst, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gbrent@ucla.edu FU VA Merit Review funds; Cedars Sinai Clinical Scholars Program FX G.A. Brent is supported by VA Merit Review funds. A. Milanesi is supported by the Cedars Sinai Clinical Scholars Program. NR 54 TC 8 Z9 10 U1 2 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD OCT PY 2011 VL 18 IS 5 BP 304 EP 309 DI 10.1097/MED.0b013e32834a91d1 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 814KD UT WOS:000294448700004 PM 21841481 ER PT J AU Oliva, EM Maisel, NC Gordon, AJ Harris, AHS AF Oliva, Elizabeth M. Maisel, Natalya C. Gordon, Adam J. Harris, Alex H. S. TI Barriers to Use of Pharmacotherapy for Addiction Disorders and How to Overcome Them SO CURRENT PSYCHIATRY REPORTS LA English DT Article DE Pharmacotherapy; Pharmacologic interventions; Addiction; Substance dependence; Medication-assisted treatment; Substance abuse treatment; Alcohol; Opioids; Barriers; Facilitators ID SUBSTANCE-ABUSE TREATMENT; RANDOMIZED CONTROLLED-TRIALS; PSYCHIATRY WFSBP GUIDELINES; OPIOID-DEPENDENT PATIENTS; ALCOHOL-USE DISORDERS; BUPRENORPHINE TREATMENT; MAINTENANCE THERAPY; PRIMARY-CARE; TREATMENT ORGANIZATIONS; SUBSTITUTION TREATMENT AB Substance use disorders are highly prevalent, debilitating conditions for which effective pharmacotherapies exist with a broad evidence base, yet pharmacotherapy for the treatment of addiction disorders is underutilized. The goals of this review are to describe the barriers that may contribute to poor adoption and utilization of pharmacotherapy for alcohol and opioid dependence at the system, provider, and patient level and to discuss ways to overcome those barriers. Multifaceted efforts directed at all three levels may be needed to speed pharmacotherapy adoption. More research is needed to help us better understand barriers from patients' perspectives. Strategies to promote adoption of pharmacotherapy for addiction disorders should be modified to fit the needs of the practice, system, and individual patients. Pharmacotherapy is a valuable tool in the clinical armamentarium of addiction treatment; thus, overcoming barriers to implementation may improve clinical and social outcomes. C1 [Oliva, Elizabeth M.; Maisel, Natalya C.; Harris, Alex H. S.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Hlth Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA. [Gordon, Adam J.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. RP Oliva, EM (reprint author), VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, 795 Willow Rd,Mailcode 152 MPD, Menlo Pk, CA 94025 USA. EM elizabeth.oliva@va.gov; natalya.maisel@va.gov; adam.gordon@va.gov; alexander.harris2@va.gov FU NIMH NIH HHS [R25 MH080916] NR 76 TC 27 Z9 27 U1 3 U2 13 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 OCT PY 2011 VL 13 IS 5 BP 374 EP 381 DI 10.1007/s11920-011-0222-2 PG 8 WC Psychiatry SC Psychiatry GA 815CR UT WOS:000294504200010 PM 21773951 ER PT J AU Moscariello, A Takx, RAP Schoepf, UJ Renker, M Zwerner, PL O'Brien, TX Allmendinger, T Vogt, S Schmidt, B Savino, G Fink, C Bonomo, L Henzler, T AF Moscariello, Antonio Takx, Richard A. P. Schoepf, U. Joseph Renker, Matthias Zwerner, Peter L. O'Brien, Terrence X. Allmendinger, Thomas Vogt, Sebastian Schmidt, Bernhard Savino, Giancarlo Fink, Christian Bonomo, Lorenzo Henzler, Thomas TI Coronary CT angiography: image quality, diagnostic accuracy, and potential for radiation dose reduction using a novel iterative image reconstruction technique-comparison with traditional filtered back projection SO EUROPEAN RADIOLOGY LA English DT Article DE Iterative reconstruction; Coronary CT angiography; Image noise; Radiation dose; Image quality ID DUAL-SOURCE CT; SPIRAL COMPUTED-TOMOGRAPHY; ARTERY-DISEASE; TEMPORAL-RESOLUTION; CARDIAC CT; PERFORMANCE; NOISE; CHEST; METAANALYSIS AB Objectives To compare image noise, image quality and diagnostic accuracy of coronary CT angiography (cCTA) using a novel iterative reconstruction algorithm versus traditional filtered back projection (FBP) and to estimate the potential for radiation dose savings. Methods Sixty five consecutive patients (48 men; 59.3 +/- 7.7 years) prospectively underwent cCTA and coronary catheter angiography (CCA). Full radiation dose data, using all projections, were reconstructed with FBP. To simulate image acquisition at half the radiation dose, 50% of the projections were discarded from the raw data. The resulting half-dose data were reconstructed with sinogram-affirmed iterative reconstruction (SAFIRE). Full-dose FBP and half-dose iterative reconstructions were compared with regard to image noise and image quality, and their respective accuracy for stenosis detection was compared against CCA. Results Compared with full-dose FBP, half-dose iterative reconstructions showed significantly (p = 0.001 - p = 0.025) lower image noise and slightly higher image quality. Iterative reconstruction improved the accuracy of stenosis detection compared with FBP (per-patient: accuracy 96.9% vs. 93.8%, sensitivity 100% vs. 100%, specificity 94.6% vs. 89.2%, NPV 100% vs. 100%, PPV 93.3% vs. 87.5%). Conclusions Iterative reconstruction significantly reduces image noise without loss of diagnostic information and holds the potential for substantial radiation dose reduction from cCTA. C1 [Moscariello, Antonio; Takx, Richard A. P.; Schoepf, U. Joseph; Renker, Matthias; Zwerner, Peter L.; O'Brien, Terrence X.; Fink, Christian; Henzler, Thomas] Med Univ S Carolina, Heart & Vasc Ctr, Charleston, SC 29425 USA. [Moscariello, Antonio; Savino, Giancarlo; Bonomo, Lorenzo] Univ Cattolica Sacro Cuore, Dept Bioimaging & Radiol Sci, A Gemelli Hosp, I-00168 Rome, Italy. [Takx, Richard A. P.] Maastricht Univ Med Ctr, Dept Radiol, Maastricht, Netherlands. [O'Brien, Terrence X.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Allmendinger, Thomas; Schmidt, Bernhard] Siemens AG, Healthcare Sect, Forchheim, Germany. [Vogt, Sebastian] Siemens Med Solut USA, Malvern, PA USA. [Fink, Christian; Henzler, Thomas] Univ Heidelberg, Inst Clin Radiol & Nucl Med, Univ Med Ctr Mannheim, Med Fac Mannheim, Heidelberg, 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 FU Bayer-Schering; Bracco; General Electric, Medrad; Siemens; Department of Veterans Affairs FX UJS is a consultant for and receives research support from Bayer-Schering, Bracco, General Electric, Medrad, and Siemens. TA, SV, and BS are employees of Siemens Healthcare. The other authors have no conflict of interest to disclose.; This study was supported in part by the Research and Development Program of the Department of Veterans Affairs. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 36 TC 159 Z9 197 U1 1 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD OCT PY 2011 VL 21 IS 10 BP 2130 EP 2138 DI 10.1007/s00330-011-2164-9 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 814QD UT WOS:000294471100013 PM 21611758 ER PT J AU Majumder, S Richardson, A Strong, R Oddo, S AF Majumder, Smita Richardson, Arlan Strong, Randy Oddo, Salvatore TI Inducing Autophagy by Rapamycin Before, but Not After, the Formation of Plaques and Tangles Ameliorates Cognitive Deficits SO PLOS ONE LA English DT Article ID EXACERBATES TAU PATHOLOGY; P70 S6 KINASE; ALZHEIMERS-DISEASE; A-BETA; LIFE-SPAN; AMYLOID-BETA; MOUSE MODEL; IN-VIVO; SIGNALING PATHWAY; TRANSGENIC MODEL AB Previous studies have shown that inducing autophagy ameliorates early cognitive deficits associated with the build-up of soluble amyloid-beta (A beta). However, the effects of inducing autophagy on plaques and tangles are yet to be determined. While soluble A beta and tau represent toxic species in Alzheimer's disease (AD) pathogenesis, there is well documented evidence that plaques and tangles also are detrimental to normal brain function. Thus, it is critical to assess the effects of inducing autophagy in an animal model with established plaques and tangles. Here we show that rapamycin, when given prophylactically to 2-month-old 3xTg-AD mice throughout their life, induces autophagy and significantly reduces plaques, tangles and cognitive deficits. In contrast, inducing autophagy in 15-month-old 3xTg-AD mice, which have established plaques and tangles, has no effects on AD-like pathology and cognitive deficits. In conclusion, we show that autophagy induction via rapamycin may represent a valid therapeutic strategy in AD when administered early in the disease progression. C1 [Majumder, Smita; Oddo, Salvatore] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Majumder, Smita; Richardson, Arlan; Strong, Randy; Oddo, Salvatore] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Richardson, Arlan; Strong, Randy] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. [Richardson, Arlan; Strong, Randy] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. RP Majumder, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. EM oddo@uthscsa.edu FU National Institute on Aging (NIA) [K99/R00AG29729-4, R01AG037637]; William and Ella Owens Medical Research Foundation; [RC2AG036613] FX This work was supported by National Institute on Aging (NIA) grant awards K99/R00AG29729-4 and R01AG037637 (Oddo, Principal Investigator), RC2AG036613 (Richardson, Principal Investigator, Strong and Oddo, Project Co-leaders), and by an award from the William and Ella Owens Medical Research Foundation to S.O. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 95 TC 127 Z9 133 U1 4 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 28 PY 2011 VL 6 IS 9 AR e25416 DI 10.1371/journal.pone.0025416 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 834CT UT WOS:000295936900063 PM 21980451 ER PT J AU Maher, AR Maglione, M Bagley, S Suttorp, M Hu, JH Ewing, B Wang, Z Timmer, M Sultzer, D Shekelle, PG AF Maher, Alicia Ruelaz Maglione, Margaret Bagley, Steven Suttorp, Marika Hu, Jian-Hui Ewing, Brett Wang, Zhen Timmer, Martha Sultzer, David Shekelle, Paul G. TI Efficacy and Comparative Effectiveness of Atypical Antipsychotic Medications for Off-Label Uses in Adults A Systematic Review and Meta-analysis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID OBSESSIVE-COMPULSIVE DISORDER; PLACEBO-CONTROLLED-TRIAL; SEROTONIN REUPTAKE INHIBITORS; GENERALIZED ANXIETY DISORDER; CONTROLLED CLINICAL-TRIAL; NURSING-HOME RESIDENTS; FUMARATE QUETIAPINE XR; DOUBLE-BLIND TRIAL; A-DOUBLE-BLIND; ALZHEIMERS-DISEASE AB Context Atypical antipsychotic medications are commonly used for off-label conditions such as agitation in dementia, anxiety, and obsessive-compulsive disorder. Objective To perform a systematic review on the efficacy and safety of atypical antipsychotic medications for use in conditions lacking approval for labeling and marketing by the US Food and Drug Administration. Data Sources and Study Selection Relevant studies published in the English language were identified by searches of 6 databases (PubMed, EMBASE, CINAHL, PsycInfo, Cochrane DARE, and CENTRAL) from inception through May 2011. Controlled trials comparing an atypical antipsychotic medication (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, asenapine, iloperidone, or paliperidone) with placebo, another atypical antipsychotic medication, or other pharmacotherapy for adult off-label conditions were included. Observational studies with sample sizes of greater than 1000 patients were included to assess adverse events. Data Extraction Independent article review and study quality assessment by 2 investigators. Data Synthesis Of 12 228 citations identified, 162 contributed data to the efficacy review. Among 14 placebo-controlled trials of elderly patients with dementia reporting a total global outcome score that includes symptoms such as psychosis, mood alterations, and aggression, small but statistically significant effects sizes ranging from 0.12 and 0.20 were observed for aripiprazole, olanzapine, and risperidone. For generalized anxiety disorder, a pooled analysis of 3 trials showed that quetiapine was associated with a 26% greater likelihood of a favorable response (defined as at least 50% improvement on the Hamilton Anxiety Scale) compared with placebo. For obsessive-compulsive disorder, risperidone was associated with a 3.9-fold greater likelihood of a favorable response (defined as a 25% improvement on the Yale-Brown Obsessive Compulsive Scale) compared with placebo. In elderly patients, adverse events included an increased risk of death (number needed to harm [NNH]=87), stroke (NNH=53 for risperidone), extrapyramidal symptoms (NNH=10 for olanzapine; NNH=20 for risperidone), and urinary tract symptoms (NNH range=16-36). In nonelderly adults, adverse events included weight gain (particularly with olanzapine), fatigue, sedation, akathisia (for aripiprazole), and extrapyramidal symptoms. Conclusions Benefits and harms vary among atypical antipsychotic medications for off-label use. For global behavioral symptom scores associated with dementia in elderly patients, small but statistically significant benefits were observed for aripiprazole, olanzapine, and risperidone. Quetiapine was associated with benefits in the treatment of generalized anxiety disorder, and risperidone was associated with benefits in the treatment of obsessive-compulsive disorder; however, adverse events were common. JAMA. 2011;306(12):1359-1369 C1 [Maher, Alicia Ruelaz; Maglione, Margaret; Suttorp, Marika; Hu, Jian-Hui; Ewing, Brett; Wang, Zhen; Timmer, Martha; Shekelle, Paul G.] So Calif Evidence Based Practice Ctr, RAND Hlth, Santa Monica, CA 90401 USA. [Bagley, Steven] VA Palo Alto Healthcare Syst, Palo Alto, CA USA. [Sultzer, David; Shekelle, Paul G.] W Los Angeles VA Med Ctr, Los Angeles, CA USA. [Sultzer, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Maher, AR (reprint author), So Calif Evidence Based Practice Ctr, RAND Hlth, 1776 Main St, Santa Monica, CA 90401 USA. EM Alicia.Ruelaz@cshs.org RI Wang, Zhen/D-5991-2013 OI Wang, Zhen/0000-0002-9368-6149 FU Eli Lilly; RAND Corporation; Agency for Healthcare Research and Quality [HHSA2902007100621]; Department of Veterans Affairs FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Sultzer reported that he received research support for an Alzheimer disease study from Eli Lilly (no direct or indirect salary was paid to him) and consulting fees from RAND Corporation for his work as member of a technical expert panel for the Agency for Healthcare Research and Quality that performed the initial analysis. No other disclosures were reported.; This article is based on research conducted by the Southern California Evidence-Based Practice Center under contract HHSA2902007100621 with the Agency for Healthcare Research and Quality. This work was commissioned by the Agency for Healthcare Research and Quality as an update to an earlier report. Drs Sultzer and Shekelle are also supported by the Department of Veterans Affairs. NR 99 TC 193 Z9 201 U1 8 U2 38 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 SEP 28 PY 2011 VL 306 IS 12 BP 1359 EP 1369 DI 10.1001/jama.2011.1360 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 825FQ UT WOS:000295257000025 PM 21954480 ER PT J AU Baliram, R Latif, R Berkowitz, J Frid, S Colaianni, G Sun, L Zaidi, M Davies, TF AF Baliram, Ramkumarie Latif, Rauf Berkowitz, Joshua Frid, Simon Colaianni, Graziana Sun, Li Zaidi, Mone Davies, Terry F. TI Thyroid-stimulating hormone induces a Wnt-dependent, feed-forward loop for osteoblastogenesis in embryonic stem cell cultures SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BONE-MARROW-CELLS; RECOMBINANT TSH; PKC-DELTA; IN-VITRO; RECEPTOR; PATHWAY; OSTEOPROTEGERIN; DIFFERENTIATION; EXPRESSION; WOMEN AB We have shown that the anterior pituitary hormone, thyroid-stimulating hormone (TSH), can bypass the thyroid to exert a direct protective effect on the skeleton. Thus, we have suggested that a low TSH level may contribute to the bone loss of hyperthyroidism that has been attributed traditionally to high thyroid hormone levels. Earlier mouse genetic, cell-based, and clinical studies together have established that TSH inhibits osteoclastic bone resorption. However, the direct influence of TSH on the osteoblast has remained unclear. Here, we have used a model system developed from murine ES cells, induced to form mature mineralizing osteoblasts, and show that TSH stimulates osteoblast differentiation primarily through the activation of protein kinase C delta and the up-regulation of the noncanonical Wnt components frizzled and Wnt5a. We predict that a TSH-induced, fast-forward short loop in bone marrow permits Wnt5a production, which, in addition to enhancing osteoblast differentiation, also stimulates osteoprotegerin secretion to attenuate bone resorption by neighboring osteoclasts. We surmise that this loop should uncouple bone formation from bone resorption with a net increase in bone mass, which is what has been observed upon injecting TSH. C1 [Baliram, Ramkumarie; Latif, Rauf; Berkowitz, Joshua; Frid, Simon; Davies, Terry F.] Mt Sinai Sch Med, Thyroid Res Lab, New York, NY 10029 USA. [Colaianni, Graziana; Sun, Li; Zaidi, Mone; Davies, Terry F.] Mt Sinai Sch Med, Mt Sinai Bone Program, New York, NY 10029 USA. [Colaianni, Graziana; Sun, Li; Zaidi, Mone; Davies, Terry F.] James J Peters VA Med Ctr, New York, NY 10029 USA. RP Davies, TF (reprint author), Mt Sinai Sch Med, Thyroid Res Lab, New York, NY 10029 USA. EM terry.davies@mssm.edu OI Colaianni, Graziana/0000-0001-8501-5399 FU National Institutes of Health [DK080459, DK069713, DK052464, AG40132, DK70526]; David Owen Segal Endowment; VA Merit Review Program FX This work was supported in part by National Institutes of Health Grants DK080459 (M.Z., L. S., and T. F. D.), DK069713 and DK052464 (T. F. D.), AG40132 and DK70526 (M.Z.), the David Owen Segal Endowment, and the VA Merit Review Program (T. F. D.). NR 29 TC 18 Z9 19 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 27 PY 2011 VL 108 IS 39 BP 16277 EP 16282 DI 10.1073/pnas.1110286108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 825FB UT WOS:000295255300034 PM 21911383 ER PT J AU Zhang, YT Zhou, L Gellad, W AF Zhang, Yuting Zhou, Lei Gellad, Walid TI The True Cost of Discounted Medication Programs reply SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 [Zhang, Yuting; Zhou, Lei] Univ Pittsburgh, Dept Hlth Policy & Management, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Gellad, Walid] Univ Pittsburgh, Sch Med, Div Gen Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Gellad, Walid] RAND Corp, Pittsburgh, PA USA. RP Zhang, YT (reprint author), Univ Pittsburgh, Dept Hlth Policy & Management, Grad Sch Publ Hlth, 130 De Soto St,Crabtree Hall A664, Pittsburgh, PA 15261 USA. EM ytzhang@pitt.edu OI Zhang, Yuting/0000-0002-6460-6779 NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 26 PY 2011 VL 171 IS 17 BP 1595 EP 1596 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 824RY UT WOS:000295221000025 ER PT J AU Casarett, D Richardson, D Smith, D Johnson, M AF Casarett, David Richardson, Diane Smith, Dawn Johnson, Megan TI Palliative Care Units: The Best Option for the Most Distressed reply SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 [Casarett, David] Univ Penn, Perelman Sch Med, Div Geriatr Med, Philadelphia, PA 19104 USA. [Richardson, Diane; Smith, Dawn; Johnson, Megan] Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Casarett, D (reprint author), Univ Penn, Perelman Sch Med, Div Geriatr Med, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM casarett@mail.med.upenn.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 26 PY 2011 VL 171 IS 17 BP 1601 EP 1602 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 824RY UT WOS:000295221000036 ER PT J AU Xiang, XJ Huang, W Haile, CN Kosten, TA AF Xiang, Xiaojun Huang, Wen Haile, Colin N. Kosten, Therese A. TI Hippocampal GluR1 associates with behavior in the elevated plus maze and shows sex differences SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE CREB; AMPA; Anxiety; Female; Rat ID ELEMENT-BINDING PROTEIN; ANXIETY-RELATED BEHAVIOR; ESTROUS-CYCLE; FEMALE RATS; AMPA RECEPTORS; DEFICIENT MICE; CA1 REGION; IN-VIVO; CREB; MEMORY AB The hippocampus is involved in anxiety as well as spatial memory formation and is sexually dimorphic. Female rats typically show less anxiety in elevated plus maze procedure (EPM), a standard animal model of anxiety. Many intracellular proteins, including alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 and the cyclic AMP response element-binding protein (CREB), in hippocampus contribute to memory formation. However, less is known about the roles for hippocampal GluR1 and CREB in anxiety. We examined behavior in EPM in male and female rats and obtained hippocampal tissue samples to determine levels of GluR1 and CREB with western blots. EPM results showed that female rats exhibited less anxiety-like behaviors than male rats. Further, behaviors in EPM were significantly correlated with hippocampal GluR1 levels, but not with CREB. Yet, both proteins showed sex differences with lower levels in female rats. These data not only suggest some potential bases for sex differences in behaviors to which the hippocampus contributes but demonstrate that there is a strong association between hippocampal GluR1 levels and anxiety as assessed with EPM. (C) 2011 Elsevier B.V. All rights reserved. C1 [Xiang, Xiaojun; Huang, Wen; Haile, Colin N.; Kosten, Therese A.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Xiang, Xiaojun; Huang, Wen; Haile, Colin N.; Kosten, Therese A.] Michael E Debakey Vet Adm Med Ctr, Houston, TX 77030 USA. [Xiang, Xiaojun] Cent S Univ, Mental Hlth Inst, Xiangya Hosp 2, Changsha, Hunan, Peoples R China. RP Kosten, TA (reprint author), Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM tkosten@bcm.edu OI Haile, Colin/0000-0001-8293-7291 FU National Institute on Drug Abuse [DA 020117]; Chinese government FX This research was supported by a National Institute on Drug Abuse grant to TAK (DA 020117). XX was supported by a fellowship from the Chinese government. We thank Dr. Alicia Walf for her expert guidance in the elevated plus maze procedure and its analysis. NR 44 TC 15 Z9 15 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD SEP 23 PY 2011 VL 222 IS 2 BP 326 EP 331 DI 10.1016/j.bbr.2011.03.068 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 780ED UT WOS:000291836400008 PM 21497621 ER PT J AU Ramos, OV Torterolo, P Lim, V Chase, MH Sampogna, S Yamuy, J AF Ramos, Oscar V. Torterolo, Pablo Lim, Vincent Chase, Michael H. Sampogna, Sharon Yamuy, Jack TI The role of mesopontine NGF in sleep and wakefulness SO BRAIN RESEARCH LA English DT Article DE Neurotrophin; Brainstem; Reticular formation; LDT; PPT; Immunohistochemistry ID NERVE GROWTH-FACTOR; PEDUNCULOPONTINE TEGMENTAL NUCLEI; INDUCED ACTIVE SLEEP; EYE-MOVEMENT SLEEP; NEUROTROPHIN-LIKE IMMUNOREACTIVITY; PONTINE RETICULAR-FORMATION; RAT SYMPATHETIC NEURONS; REM-SLEEP; CHOLINE-ACETYLTRANSFERASE; BRAIN-STEM AB The microinjection of nerve growth factor (NGF) into the cat pontine tegmentum rapidly induces rapid eye movement (REM) sleep. To determine if NGF is involved in naturally-occurring REM sleep, we examined whether it is present in mesopontine cholinergic structures that promote the initiation of REM sleep, and whether the blockade of NGF production in these structures suppresses REM sleep. We found that cholinergic neurons in the cat dorso-lateral mesopontine tegmentum exhibited NGF-like immunoreactivity. In addition, the microinjection of an oligodeoxyribonucleotide (OD) directed against cat NGF mRNA into this region resulted in a reduction in the time spent in REM sleep in conjunction with an increase in the time spent in wakefulness. Sleep and wakefulness returned to baseline conditions 2 to 5 days after antisense OD administration. The preceding antisense OD-induced effects occurred in conjunction with the suppression of NGF-like immunoreactivity within the site of antisense OD injection. These data support the hypothesis that NGF is involved in the modulation of naturally-occurring sleep and wakefulness. (C) 2011 Elsevier B.V. All rights reserved. C1 [Yamuy, Jack] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Ramos, Oscar V.; Lim, Vincent; Chase, Michael H.; Sampogna, Sharon] Websci Int, Los Angeles, CA 90024 USA. [Chase, Michael H.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. [Torterolo, Pablo] Univ Republica, Fac Med, Dept Fisiol, Montevideo, Uruguay. RP Yamuy, J (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM jyamuy@ucla.edu FU USPHS [MH59284] FX Supported by USPHS grant MH59284. The authors thank Trent Wenzel for his excellent technical assistance. NR 64 TC 1 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 21 PY 2011 VL 1413 BP 9 EP 23 DI 10.1016/j.brainres.2011.06.066 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 825QM UT WOS:000295297200002 PM 21840513 ER PT J AU Lo Re, V Teal, V Localio, AR Amorosa, VK Kaplan, DE Gross, R AF Lo Re, Vincent, III Teal, Valerie Localio, A. Russell Amorosa, Valerianna K. Kaplan, David E. Gross, Robert TI Relationship Between Adherence to Hepatitis C Virus Therapy and Virologic Outcomes SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID INTERFERON-ALPHA-2B PLUS RIBAVIRIN; INITIATED ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; PEGINTERFERON ALPHA-2A; COMBINATION THERAPY; SUSTAINED RESPONSE; PHARMACY RECORDS; VIRAL LOAD; INFECTION; COMPLICATIONS AB Background: Adherence to therapy with pegylated interferon and ribavirin for hepatitis C virus (HCV) infection has been incompletely examined. Objective: To evaluate the relationship between adherence to HCV therapy and early and sustained virologic response, assess changes in adherence over time, and examine risk factors for nonadherence. Design: Retrospective cohort study. Setting: National Veterans Affairs Hepatitis C Clinical Case Registry. Patients: 5706 HCV-infected patients (genotypes 1, 2, 3, or 4) with at least 1 prescription for both pegylated interferon and ribavirin between 2003 and 2006 and HCV RNA results before and after treatment initiation. Measurements: Adherence was calculated over 12-week intervals by using pharmacy refill data. End points included early virologic response (decrease of >= 2 log(10) HCV RNA at 12 weeks) and sustained virologic response (undetectable HCV RNA 24 weeks after the end of treatment). Results: Early virologic response increased with higher levels of adherence to ribavirin therapy over the initial 12 weeks (patients with HCV genotype 1 or 4, 25 of 68 [37%] with <= 40% adherence vs. 1367 of 2187 [63%] with 91% to 100% adherence [P < 0.001]; patients with HCV genotype 2 or 3, 12 of 18 [67%] with <= 40% adherence vs. 651 of 713 [91%] with 91% to 100% adherence [P < 0.001]). Among patients with HCV genotype 1 or 4, sustained response increased with higher adherence to ribavirin therapy over the second, third, and fourth 12-week intervals. Results were similar for adherence to interferon therapy. Mean adherence to therapy with interferon and ribavirin decreased by 3.4 and 6.6 percentage points per 12-week interval, respectively (P for trend < 0.001 for each drug). Patients who received growth factors or thyroid medications during treatment had higher mean adherence to antiviral therapy. Limitation: This was an observational study without standardized timing for outcome measurements. Conclusion: Early and sustained virologic responses increased with higher levels of adherence to interferon and ribavirin therapy. Adherence to therapy with both antivirals decreased over time, but more so for ribavirin. C1 [Lo Re, Vincent, III] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 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 Lo Re, Vincent/N-7817-2015 OI Teal, Valerie/0000-0001-7116-5353 FU Department of Veterans Affairs; National Institutes of Health [K01 AI070001]; Agency for Healthcare Research and Quality Centers for Education and Research on Therapeutics [HS10399] FX This material is based on work supported in part by the Department of Veterans Affairs. The contents do not represent the views of the Department of Veterans Affairs or the U.S. Government.; By grant K01 AI070001 from the National Institutes of Health (Dr. Lo Re), grant HS10399 from the Agency for Healthcare Research and Quality Centers for Education and Research on Therapeutics cooperative agreement (Drs. Lo Re, Localio, and Gross), and a Department of Veterans Affairs Competitive Pilot Project Fund grant (Drs. Lo Re and Amorosa). NR 37 TC 27 Z9 27 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 SEP 20 PY 2011 VL 155 IS 6 BP 353 EP U46 DI 10.7326/0003-4819-155-6-201109200-00003 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 822HA UT WOS:000295033400014 PM 21930852 ER PT J AU Chou, R Arora, B Dana, T Fu, RW Walker, M Humphrey, L AF Chou, Roger Arora, Bhaskar Dana, Tracy Fu, Rongwei Walker, Miranda Humphrey, Linda TI Screening Asymptomatic Adults With Resting or Exercise Electrocardiography: A Review of the Evidence for the US Preventive Services Task Force SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID CORONARY-HEART-DISEASE; MIDDLE-AGED MEN; LEFT-VENTRICULAR HYPERTROPHY; FACTOR INTERVENTION TRIAL; ST-SEGMENT DEPRESSION; ALL-CAUSE MORTALITY; APPARENTLY HEALTHY-MEN; CARDIOVASCULAR RISK-FACTORS; SILENT-MYOCARDIAL-ISCHEMIA; T-WAVE ABNORMALITIES AB Background: Coronary heart disease is the leading cause of death in adults. Screening for abnormalities by using resting or exercise electrocardiography (ECG) might help identify persons who would benefit from interventions to reduce cardiovascular risk. Purpose: To update the 2004 U. S. Preventive Services Task Force evidence review on screening for resting or exercise ECG abnormalities in asymptomatic adults. Data Sources: MEDLINE (2002 through January 2011), the Cochrane Library database (through the fourth quarter of 2010), and reference lists. Study Selection: Randomized, controlled trials and prospective cohort studies. Data Extraction: Investigators abstracted details about the study population, study design, data analysis, follow-up, and results and assessed quality by using predefined criteria. Data Synthesis: No study evaluated clinical outcomes or use of risk-reducing therapies after screening versus no screening. No study estimated how accurately resting or exercise electrocardiography classified participants into high-, intermediate-, or low-risk groups, compared with traditional risk factor assessment alone. Sixty-three prospective cohort studies evaluated abnormalities on resting or exercise ECG as predictors of cardiovascular events after adjustment for traditional risk factors. Abnormalities on resting ECG (ST-segment or T-wave abnormalities, left ventricular hypertrophy, bundle branch block, or left-axis deviation) or exercise ECG (ST-segment depression with exercise, chronotropic incompetence, abnormal heart rate recovery, or decreased exercise capacity) were associated with increased risk (pooled hazard ratio estimates, 1.4 to 2.1). Evidence on harms was limited, but direct harms seemed minimal (for resting ECG) or small (for exercise ECG). No study estimated harms from subsequent testing or interventions, although rates of angiography after exercise ECG ranged from 0.6% to 2.9%. Limitations: Only English-language studies were included. Statistical heterogeneity was present in several of the pooled analyses. Conclusion: Abnormalities on resting or exercise ECG are associated with an increased risk for subsequent cardiovascular events after adjustment for traditional risk factors, but the clinical implications of these findings are unclear. C1 [Chou, Roger] Oregon Hlth & Sci Univ, Oregon Evidence Based Practice Ctr, Mailcode BICC, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Chou, R (reprint author), Oregon Hlth & Sci Univ, Oregon Evidence Based Practice Ctr, Mailcode BICC, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM chour@ohsu.edu FU Agency for Healthcare Research and Quality [HHSA-290-2007-10057-I-EPC3] FX By contract number HHSA-290-2007-10057-I-EPC3, Task Order No. 3, from the Agency for Healthcare Research and Quality. NR 100 TC 63 Z9 63 U1 1 U2 8 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 SEP 20 PY 2011 VL 155 IS 6 BP 375 EP U74 DI 10.7326/0003-4819-155-6-201109200-00006 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 822HA UT WOS:000295033400017 PM 21930855 ER PT J AU Lucero, CA Oda, G Cox, K Maldonado, F Lombardo, J Wojcik, R Holodniy, M AF Lucero, Cynthia A. Oda, Gina Cox, Kenneth Maldonado, Frank Lombardo, Joseph Wojcik, Richard Holodniy, Mark TI Enhanced health event detection and influenza surveillance using a joint Veterans Affairs and Department of Defense biosurveillance application SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article ID COMMUNITY-BASED EPIDEMICS; SYNDROMIC SURVEILLANCE; OUTBREAK DETECTION; EARLY NOTIFICATION; SYSTEM AB Background: The establishment of robust biosurveillance capabilities is an important component of the U.S. strategy for identifying disease outbreaks, environmental exposures and bioterrorism events. Currently, U.S. Departments of Defense (DoD) and Veterans Affairs (VA) perform biosurveillance independently. This article describes a joint VA/DoD biosurveillance project at North Chicago-VA Medical Center (NC-VAMC). The Naval Health Clinics-Great Lakes facility physically merged with NC-VAMC beginning in 2006 with the full merger completed in October 2010 at which time all DoD care and medical personnel had relocated to the expanded and remodeled NC-VAMC campus and the combined facility was renamed the Lovell Federal Health Care Center (FHCC). The goal of this study was to evaluate disease surveillance using a biosurveillance application which combined data from both populations. Methods: A retrospective analysis of NC-VAMC/Lovell FHCC and other Chicago-area VAMC data was performed using the ESSENCE biosurveillance system, including one infectious disease outbreak (Salmonella/Taste of Chicago-July 2007) and one weather event (Heat Wave-July 2006). Influenza-like-illness (ILI) data from these same facilities was compared with CDC/Illinois Sentinel Provider and Cook County ESSENCE data for 2007-2008. Results: Following consolidation of VA and DoD facilities in North Chicago, median number of visits more than doubled, median patient age dropped and proportion of females rose significantly in comparison with the pre-merger NC-VAMC facility. A high-level gastrointestinal alert was detected in July 2007, but only low-level alerts at other Chicago-area VAMCs. Heat-injury alerts were triggered for the merged facility in June 2006, but not at the other facilities. There was also limited evidence in these events that surveillance of the combined population provided utility above and beyond the VA-only and DoD-only components. Recorded ILI activity for NC-VAMC/Lovell FHCC was more pronounced in the DoD component, likely due to pediatric data in this population. NCVAMC/Lovell FHCC had two weeks of ILI activity exceeding both the Illinois State and East North Central Regional baselines, whereas Hines VAMC had one and Jesse Brown VAMC had zero. Conclusions: Biosurveillance in a joint VA/DoD facility showed potential utility as a tool to improve surveillance and situational awareness in an area with Veteran, active duty and beneficiary populations. Based in part on the results of this pilot demonstration, both agencies have agreed to support the creation of a combined VA/DoD ESSENCE biosurveillance system which is now under development. C1 [Lucero, Cynthia A.; Oda, Gina; Holodniy, Mark] US Dept Vet Affairs, Off Publ Hlth, Off Publ Hlth Surveillance & Res, Palo Alto, CA 94304 USA. [Cox, Kenneth] Armed Forces Hlth Surveillance Ctr, Med Informat Project, Silver Spring, MD 20910 USA. [Cox, Kenneth] Armed Forces Hlth Surveillance Ctr, Special Project, Silver Spring, MD 20910 USA. [Maldonado, Frank] US Dept Vet Affairs, Captain James A Lovell Fed Hlth Care Ctr, N Chicago, IL 60064 USA. [Lombardo, Joseph; Wojcik, Richard] Johns Hopkins Univ, Appl Phys Lab, ESSENCE Grp, Laurel, MD 20723 USA. RP Lucero, CA (reprint author), US Dept Vet Affairs, Off Publ Hlth, Off Publ Hlth Surveillance & Res, 3801 Miranda Ave 132, Palo Alto, CA 94304 USA. EM cynthia.lucero@va.gov NR 37 TC 6 Z9 7 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD SEP 19 PY 2011 VL 11 AR 56 DI 10.1186/1472-6947-11-56 PG 12 WC Medical Informatics SC Medical Informatics GA 832DE UT WOS:000295781100001 PM 21929813 ER PT J AU Thangasamy, A Rogge, J Krishnegowda, NK Freeman, JW Ammanamanchi, S AF Thangasamy, Amalraj Rogge, Jessica Krishnegowda, Naveen K. Freeman, James W. Ammanamanchi, Sudhakar TI Novel Function of Transcription Factor Nrf2 as an Inhibitor of RON Tyrosine Kinase Receptor-mediated Cancer Cell Invasion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OXIDATIVE STRESS; BREAST-CANCER; ACTIVATION; MICE; SULFORAPHANE; SENSITIVITY; PREVENTION; MUTATIONS AB Recepteur d' origine nantais (RON), a tyrosine kinase receptor, is aberrantly expressed in human tumors and promotes cancer cell invasion. RON receptor activation is also associated with resistance to tamoxifen treatment in breast cancer cells. Nrf2 is a positive regulator of cytoprotective genes. Using chromatin immunoprecipitation (ChIP) and site-directed mutagenesis studies of the RON promoter, we identified Nrf2 as a negative regulator of RON gene expression. High Nrf2 and low RON expression was observed in normal mammary tissue whereas high RON and low or undetectable expression of Nrf2 was observed in breast tumors. The Nrf2 inducer sulforaphane (SFN) as well as ectopic Nrf2 expression or knock-down of the Nrf2 negative regulator keap1, which stabilizes Nrf2, inhibited RON expression and invasion of carcinoma cells. Consequently, our studies identified a novel functional role for Nrf2 as a "repressor" and RON kinase as a molecular target of SFN, which mediates the anti-tumor effects of SFN. These results are not limited to breast cancer cells since the Nrf2 inducer SFN stabilized Nrf2 and inhibited RON expression in carcinoma cells from various tumor types. C1 [Thangasamy, Amalraj; Rogge, Jessica; Krishnegowda, Naveen K.; Freeman, James W.; Ammanamanchi, Sudhakar] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol Med Oncol, San Antonio, TX 78229 USA. [Freeman, James W.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78229 USA. RP Ammanamanchi, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol Med Oncol, San Antonio, TX 78229 USA. EM sammanamanchi@hotmail.com FU Veterans Administration FX This work was supported by the Veterans Administration Merit Award (to J. W. F.). NR 20 TC 14 Z9 15 U1 2 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 SEP 16 PY 2011 VL 286 IS 37 BP 32115 EP 32122 DI 10.1074/jbc.M111.245746 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 818CK UT WOS:000294726800021 PM 21799005 ER PT J AU Mostaghel, EA Marck, BT Plymate, SR Vessella, RL Balk, S Matsumoto, AM Nelson, PS Montgomery, RB AF Mostaghel, Elahe A. Marck, Brett T. Plymate, Stephen R. Vessella, Robert L. Balk, Stephen Matsumoto, Alvin M. Nelson, Peter S. Montgomery, R. Bruce TI Resistance to CYP17A1 Inhibition with Abiraterone in Castration-Resistant Prostate Cancer: Induction of Steroidogenesis and Androgen Receptor Splice Variants SO CLINICAL CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; CYTOCHROME P450(17-ALPHA); THERAPEUTIC IMPLICATIONS; STEROIDAL INHIBITORS; ANTITUMOR-ACTIVITY; PROGRESSION; ACETATE; DEHYDROGENASE; GROWTH; ANTIANDROGEN AB Purpose: Abiraterone is a potent inhibitor of the steroidogenic enzyme CYP17A1 and suppresses tumor growth in patients with castration-resistant prostate cancer (CRPC). The effectiveness of abiraterone in reducing tumor androgens is not known, nor have mechanisms contributing to abiraterone resistance been established. Experimental Design: We treated human CRPC xenografts with abiraterone and measured tumor growth, tissue androgens, androgen receptor (AR) levels, and steroidogenic gene expression versus controls. Results: Abiraterone suppressed serum PSA levels and improved survival in two distinct CRPC xenografts: median survival of LuCaP35CR improved from 17 to 39 days (HR = 3.6, P = 0.0014) and LuCaP23CR from 14 to 24 days (HR = 2.5, P = 0.0048). Abiraterone strongly suppressed tumor androgens, with testosterone (T) decreasing from 0.49 +/- 0.22 to 0.03 +/- 0.01 pg/mg (P < 0.0001), and from 0.69 +/- 0.36 to 0.03 +/- 0.01 pg/mg (P = 0.002) in abiraterone-treated 23CR and 35CR, respectively, with comparable decreases in tissue DHT. Treatment was associated with increased expression of full-length AR (AR(FL)) and truncated AR variants (AR(FL) 2.3-fold, P = 0.008 and AR(del567es) 2.7-fold, P = 0.036 in 23 CR; AR(FL) 3.4-fold, P = 0.001 and AR(V7) 3.1-fold, P = 0.0003 in 35CR), and increased expression of the abiraterone target CYP17A1 (similar to 2.1- fold, P = 0.0001 and P = 0.028 in 23CR and 35CR, respectively) and transcript changes in other enzymes modulating steroid metabolism. Conclusions: These studies indicate that abiraterone reduces CRPC growth via suppression of intratumoral androgens and that resistance to abiraterone may occur through mechanisms that include upregulation of CYP17A1, and/or induction of AR and AR splice variants that confer ligand-independent AR transactivation. Clin Cancer Res; 17(18); 5913-25. (C) 2011 AACR. C1 [Mostaghel, Elahe A.; Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. [Mostaghel, Elahe A.; Plymate, Stephen R.; Matsumoto, Alvin M.; Nelson, Peter S.; Montgomery, R. Bruce] Univ Washington, Dept Med, Seattle, WA USA. [Marck, Brett T.; Plymate, Stephen R.; Matsumoto, Alvin M.; Montgomery, R. Bruce] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Vessella, Robert L.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Balk, Stephen] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Mostaghel, EA (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D4-100, Seattle, WA 98109 USA. EM emostagh@fhcrc.org FU Cougar Biotechnology; Prostate Cancer Foundation; Damon Runyon Cancer Research Foundation [CI-40-08]; NIH [K23 CA122820, P50 CA97186]; Cancer Center [P30 CA015704]; Veterans Affairs Research Service FX R.B. Montomery received commercial research grant from Cougar Biotechnology. The other authors disclosed no potential conflicts of interest.; Prostate Cancer Foundation (Career Development Award to E.A. Mostaghel and Synergy Award to S. Balk, R.B. Montgomery, and P. S. Nelson); Damon Runyon Cancer Research Foundation (Damon Runyon-Genentech Clinical Investigator Award CI-40-08 to E.A. Mostaghel); NIH [Career Development Award K23 CA122820 to E.A. Mostaghel; Pacific Northwest Prostate Cancer SPORE P50 CA97186 (R.L. Vessella, P. S. Nelson); the Cancer Center Support Grant to Fred Hutchinson Cancer Research Center (P30 CA015704 pilot to R.B. Montgomery)]; and the Veterans Affairs Research Service (S.R. Plymate). NR 42 TC 282 Z9 286 U1 2 U2 21 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 SEP 15 PY 2011 VL 17 IS 18 BP 5913 EP 5925 DI 10.1158/1078-0432.CCR-11-0728 PG 13 WC Oncology SC Oncology GA 821CM UT WOS:000294952400009 PM 21807635 ER PT J AU Kim, SG Veena, MS Basak, SK Han, E Tajima, T Gjertson, DW Starr, J Eidelman, O Pollard, HB Srivastava, M Srivatsan, ES Wang, MB AF Kim, Suejung G. Veena, Mysore S. Basak, Saroj K. Han, Eugene Tajima, Tracey Gjertson, David W. Starr, Joshua Eidelman, Ofer Pollard, Harvey B. Srivastava, Meera Srivatsan, Eri S. Wang, Marilene B. TI Curcumin Treatment Suppresses IKK beta Kinase Activity of Salivary Cells of Patients with Head and Neck Cancer: A Pilot Study SO CLINICAL CANCER RESEARCH LA English DT Article ID FACTOR-KAPPA-B; INDEPENDENT PATHWAY; CARCINOMA; INHIBITION; GROWTH; INTERLEUKIN-6; PROLIFERATION AB Purpose: To determine whether curcumin would inhibit I kappa B kinase beta (IKK beta) kinase activity and suppress expression of proinflammatory cytokines in head and neck squamous cell carcinoma cancer (HNSCC) patients. Experimental Design: Saliva was collected before and after subjects chewed curcumin tablets. Protein was extracted and IKK beta kinase activity measured. Interleukin (IL)-6 and IL-8 levels in the salivary supernatants were measured by ELISA. IL-6, IL-8, and other interleukin were also measured independently with ELISA to confirm the inhibitory effect of curcumin on expression and secretion of salivary cytokines. Results: Curcumin treatment led to a reduction in IKK beta kinase activity in the salivary cells of HNSCC patients ( P < 0.05). Treatment of UM-SCC1 cells with curcumin as well as with post-curcumin salivary supernatant showed a reduction of IKK beta kinase activity. Significant reduction of IL-8 levels ( P < 0.05) was seen in post-curcumin samples from patients with dental caries. Although there was reduced IL-8 expression in 8 of 21 post-curcumin samples of HNSCC patients, the data did not reach statistical significance. Saliva samples from HNSCC patients were also analyzed in a blinded fashion for expression of cytokines. IL-10, IFN-gamma, IL-12p70, and IL-2 clustered together, and granulocyte macrophage colony stimulating factor and TNF-alpha clustered together. Log(10) ratio analysis showed decrease in expression of all nine cytokines in both the salivary supernatant and salivary cells of curcumin-treated samples. Conclusions: Curcumin inhibited IKK beta kinase activity in the saliva of HNSCC patients, and this inhibition correlated with reduced expression of a number of cytokines. IKK beta kinase could be a useful biomarker for detecting the effect of curcumin in head and neck cancer. Clin Cancer Res; 17( 18); 5953-61. (C) 2011 AACR. C1 [Wang, Marilene B.] Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg, Los Angeles, CA 90095 USA. [Gjertson, David W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Kim, Suejung G.; Veena, Mysore S.; Basak, Saroj K.; Han, Eugene; Srivatsan, Eri S.; Wang, Marilene B.] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Tajima, Tracey] VA Greater Los Angeles Healthcare Syst, Dept Dent, Los Angeles, CA USA. [Starr, Joshua; Eidelman, Ofer; Pollard, Harvey B.; Srivastava, Meera] Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Starr, Joshua; Eidelman, Ofer; Pollard, Harvey B.; Srivastava, Meera] Uniformed Serv Univ Hlth Sci, Sch Med, Inst Mol Med, Bethesda, MD 20814 USA. RP Wang, MB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg, 200 UCLA Med Plaza,Suite 550, Los Angeles, CA 90095 USA. EM mbwang@ucla.edu FU VAGLAHS; West Los Angeles Surgical Education Research Center; UCLA; NIH [R21 CA116826-01]; Veterans Administration, Washington, DC FX The study was supported by funds from VAGLAHS, West Los Angeles Surgical Education Research Center, UCLA Academic Senate grant (M.B. Wang), NIH (R21 CA116826-01 to M. Wang), and Merit grant from the Veterans Administration, Washington, DC (E.S. Srivatsan). NR 20 TC 26 Z9 26 U1 0 U2 5 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 SEP 15 PY 2011 VL 17 IS 18 BP 5953 EP 5961 DI 10.1158/1078-0432.CCR-11-1272 PG 9 WC Oncology SC Oncology GA 821CM UT WOS:000294952400013 PM 21821700 ER PT J AU Kollef, MH Golan, Y Micek, ST Shorr, AF Restrepo, MI AF Kollef, Marin H. Golan, Yoav Micek, Scott T. Shorr, Andrew F. Restrepo, Marcos I. TI Appraising Contemporary Strategies to Combat Multidrug Resistant Gram-Negative Bacterial Infections-Proceedings and Data From the Gram-Negative Resistance Summit SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID VENTILATOR-ASSOCIATED PNEUMONIA; INTENSIVE-CARE-UNIT; COMBINATION ANTIBIOTIC-THERAPY; CRITICALLY-ILL PATIENTS; INADEQUATE ANTIMICROBIAL TREATMENT; BLOOD-STREAM INFECTION; PSEUDOMONAS-AERUGINOSA; DISEASES-SOCIETY; SEPTIC SHOCK; STAPHYLOCOCCUS-AUREUS AB The emerging problem of antibiotic resistance, especially among Gram-negative bacteria (GNB), has become a serious threat to global public health. Very few new antibacterial classes with activity against antibiotic-resistant GNB have been brought to market. Renewed and growing attention to the development of novel compounds targeting antibiotic-resistant GNB, as well as a better understanding of strategies aimed at preventing the spread of resistant bacterial strains and preserving the efficacy of existing antibiotic agents, has occurred. The Gram-Negative Resistance Summit convened national opinion leaders for the purpose of analyzing current literature, epidemiologic trends, clinical trial data, therapeutic options, and treatment guidelines related to the management of antibiotic-resistant GNB infections. After an in-depth analysis, the Summit investigators were surveyed with regard to 4 clinical practice statements. The results then were compared with the same survey completed by 138 infectious disease and critical care physicians and are the basis of this article. C1 [Kollef, Marin H.] Washington Univ, Sch Med, Div Pulm & Crit Care Med, St Louis, MO 63110 USA. [Golan, Yoav] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Micek, Scott T.] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Shorr, Andrew F.] Georgetown Univ, Washington, DC USA. [Shorr, Andrew F.] Washington Hosp Ctr, Washington, DC 20010 USA. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] Audie L Murphy Vet Hosp, Div Pulm & Crit Care Med, Dept Med, San Antonio, TX USA. RP Kollef, MH (reprint author), Washington Univ, Sch Med, Div Pulm & Crit Care Med, 660 S Euclid Ave,Campus Box 8052, St Louis, MO 63110 USA. EM mkollef@dom.wustl.edu RI Restrepo, Marcos/H-4442-2014 FU Consensus Medical Communication; Astellas; Sanofi Pasteur; Astrazeneca; Therafan; Forest Laboratories and Novartis; TRIUS; Covidien; BARD; National Heart, Lung, and Blood Institute [K23HL096054]; University of Colorado School of Medicine; Consensus Medical Communications; Ortho-McNeil Janssen Scientific Affairs, LLC.; Merck; Cubist; Pfizer; Johnson Johnson; National Heart, Lung, and Blood Institute; GlaxoSmithKline FX This work was supported by Consensus Medical Communication (consulting fees and travel support to M. H. K., Y. G., S. T. M., M. I. R.; payment for the development of educational presentations to S. T. M.; payment for writing manuscript to all authors); Merck (payment for lectures to M. H. K. and Y. G., manuscript preparation to M. H. K., and consultancy to Y. G.; grant support to Y. G.); Pfizer (Wyeth) (payment for lectures to M. H. K., Y. G., and M. I. R.; payment for manuscript preparation to M. H. K.; payment for consultancies to Y. G. and M. I. R.; grant support to Y. G. and S. T. M.); Astellas (payment for lectures and manuscript preparation to M. H. K., grant support to Y. G.); Sanofi Pasteur and Astrazeneca (payment for lectures and manuscript preparation to M. H. K.); Cubist (grant support to Y. G. and S. T. M.; payment for lectures to Y. G.); Vernco MedEd (payment for the development of educational presentations to S. T. M.); Ortho-McNeil-Janssen (Johnson & Johnson) (payment for board membership and consultancy to M. I. R.; grants to Y. G. and S. T. M.); Therafan (payment for board membership and consultancy to M. I. R.); Forest Laboratories and Novartis (payment for board membership to M. I. R.); TRIUS (payment for consultancy to M. I. R.); Covidien and BARD (payment for lectures to M. I. R.). M. I. R. is supported and his time partially protected by a grant from the National Heart, Lung, and Blood Institute (award no. K23HL096054).; Supplement sponsorship. This article was published as part of a supplement entitled "Appraising Contemporary Strategies to Combat Multidrug Resistant Gram-Negative Bacterial Infections-Proceedings and Data From the Gram-Negative Resistance Summit," jointly sponsored by the University of Colorado School of Medicine and Consensus Medical Communications and is supported by an educational grant from Ortho-McNeil Janssen Scientific Affairs, LLC.; Potential conflicts of interest. Yoav Golan, MD: is on the speakers' bureau for Merck, Pfizer, and Cubist; received grants and/or research support from Merck, Cubist, Pfizer, Astellas, and Johnson & Johnson; is a consultant for Merck, Pfizer, and Cubist. Marin Kollef, MD: is on the speakers' bureau for Merck, Pfizer, Astellas, Sanofi Pasteur, and AstraZeneca. Scott Micek, PharmD: no reported conflicts or financial disclosures. Marcos Restrepo, MD: is on the speakers' bureau for Covidien; received grant and/or research support from the National Heart, Lung, and Blood Institute; is also a consultant for Ortho-McNeil-Janssen (Johnson & Johnson), Forest Laboratories, Novartis, Theravance, and Pfizer (Wyeth). Andrew Shorr, MD: is on the speakers' bureau for Astellas, AstraZeneca, Boehringer Ingleheim, Covidien, and Pfizer; received grants and/or research support from Astellas, GlaxoSmithKline, and Pfizer; is a consultant for Astellas, Bayer, Bard, Cadence Pharmaceuticals, Canyon Pharmaceuticals, Johnson & Johnson, Eli Lilly and Company, Eisai Pharmaceuticals, Forest Laboratories, MedCo, and Theravance. NR 95 TC 35 Z9 36 U1 2 U2 9 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 SEP 15 PY 2011 VL 53 SU 2 BP S33 EP S55 DI 10.1093/cid/cir475 PG 23 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 813LE UT WOS:000294367300001 PM 21868447 ER PT J AU Kachadourian, R Pugazhenthi, S Velmurugan, K Backos, DS Franklin, CC McCord, JM Day, BJ AF Kachadourian, Remy Pugazhenthi, Subbiah Velmurugan, Kalpana Backos, Donald S. Franklin, Christopher C. McCord, Joe M. Day, Brian J. TI 2 ',5 '-Dihydroxychalcone-induced glutathione is mediated by oxidative stress and kinase signaling pathways SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE ROS; Nrf2; AP-1; MCF-7/AREc32; Metalloporphyrin; Free radicals ID GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; CANCER RESISTANCE PROTEIN; GLUTAMATE CYSTEINE LIGASE; HAMSTER V79 CELLS; HEME OXYGENASE-1; ANTIOXIDANT RESPONSE; MOLECULAR-MECHANISMS; INDUCED EXPRESSION; ENDOTHELIAL-CELLS; IN-VITRO AB Hydroxychalcones are naturally:occurring compounds that continue to attract considerable interest because of their anti-inflammatory and antiangiogenic properties. They have been reported to inhibit the synthesis of the inducible nitric oxide synthase and to induce the expression of heme oxygenase-1. This study examines the mechanisms by which 2',5'-dihydroxychalcone (2',5'-DHC) induces an increase in cellular glutathione (GSH) levels using a cell line stably expressing a luciferase reporter gene driven by antioxidant-response elements (MCF-7/AREc32). The 2',5'-DHC-induced increase in cellular GSH levels was partially inhibited by the catalytic antioxidant MnTDE-1,3-IP(5+), suggesting that reactive oxygen species (ROS) mediate the antioxidant adaptive response. 2',5'-DHC treatment induced phosphorylation of the c-Jun N-terminal kinase (JNK) pathway, which was also inhibited by MnTDE-1,3-IP(5+). These findings suggest a ROS-dependent activation of the AP-1 transcriptional response. However, whereas 2',5'-DHC triggered the NF-E2-related factor 2 (Nrf2) transcriptional response, cotreatment with MnTDE-1,3-IP(5+) did not decrease 2',5'-DHC-induced Nrf2/ARE activity, showing that this pathway is not dependent on ROS. Moreover, pharmacological inhibitors of mitogen-activated protein kinase (MAPK) pathways showed a role for JNK and p38MAPK in mediating the 2',5'-DHC-induced Nrf2 response. These findings suggest that the 2',5'-DHC-induced increase in GSH levels results from a combination of ROS-dependent and ROS-independent pathways. (C) 2011 Elsevier Inc. All rights reserved. C1 [Kachadourian, Remy; Day, Brian J.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Kachadourian, Remy; Pugazhenthi, Subbiah; McCord, Joe M.; Day, Brian J.] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA. [Pugazhenthi, Subbiah; Velmurugan, Kalpana] Denver VA Med Ctr, Denver, CO 80220 USA. [Backos, Donald S.; Franklin, Christopher C.; Day, Brian J.] Univ Colorado Denver, Dept Pharmaceut Sci, Aurora, CO 80045 USA. RP Day, BJ (reprint author), Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. EM dayb@njhealth.org OI Backos, Donald/0000-0001-6735-6210 FU NIH [HL755223, HL84469, ES015678, ES017582]; VA Merit Review [NEUD-004-07F] FX This work was supported by NIH Grants HL755223, HL84469, ES015678, and ES017582 to B.J. Day and VA Merit Review NEUD-004-07F to S. Pugazhenthi. The authors thank Gregory Mahaffey for his help with immunoblotting. Dr. Day is a consultant for and holds equity in Aeolus Pharmaceuticals, which is commercially developing metalloporphyrins as human therapeutic agents. NR 56 TC 10 Z9 11 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP 15 PY 2011 VL 51 IS 6 BP 1146 EP 1154 DI 10.1016/j.freeradbiomed.2011.05.041 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 813WB UT WOS:000294399800006 PM 21712085 ER PT J AU Xie, PX Kranzler, HR Krauthammer, M Cosgrove, KP Oslin, D Anton, RF Farrer, LA Picciotto, MR Krystal, JH Zhao, HY Gelernter, J AF Xie, Pingxing Kranzler, Henry R. Krauthammer, Michael Cosgrove, Kelly P. Oslin, David Anton, Raymond F. Farrer, Lindsay A. Picciotto, Marina R. Krystal, John H. Zhao, Hongyu Gelernter, Joel TI Rare Nonsynonymous Variants in Alpha-4 Nicotinic Acetylcholine Receptor Gene Protect Against Nicotine Dependence SO BIOLOGICAL PSYCHIATRY LA English DT Article DE CHRNA4; deep sequencing; imaging genetics; nicotine dependence; nonsynonymous; rare variants ID VENTRAL TEGMENTAL AREA; MULTILOCUS GENOTYPE DATA; GENOMEWIDE LINKAGE SCAN; SMOKING-BEHAVIOR; SEMISTRUCTURED ASSESSMENT; ALCOHOLISM SSADDA; DRUG-DEPENDENCE; SUBUNIT GENE; IN-VIVO; ASSOCIATION AB Background: Several studies report association of alpha-4 nicotinic acetylcholine receptors (encoded by CHRNA4) with nicotine dependence (ND). A meta-analysis of genomewide linkage studies for ND implicated a single chromosomal region, which includes CHRNA4, as genome-wide significant. Methods: After establishing that common variants are unlikely to completely account for this linkage, we investigated the distribution of CHRNA4 rare variants by sequencing the coding exons and flanking intronic regions of CHRNA4 in 209 European American (EA) ND cases and 183 EA control subjects. Because most of the rare variants that we detected (and all nonsynonymous changes) were in Exon 5, we sequenced Exon 5 in an additional 1000 ND cases and 1000 non-ND comparison subjects, both of which included equal numbers of EAs and African Americans. Results: Comparison subjects had a higher frequency of rare nonsynonymous variants in the Exon 5 region (encoding the large intercellular loop of the alpha 4 subunit; Fisher's Exact Test p = .009; association test p = .009, odds ratio = .43; weighted-sum method p = .014), indicating a protective effect against ND. Considering data from the two stages combined and only nonsynonymous variants predicted to alter protein function, the association was stronger (Fisher's Exact Test p = .005; association test p = .008, odds ratio = .29; weighted-sum method p = .005). Single-photon emission computed tomography imaging results were consistent with functionality. Conclusions: CHRNA4 functional rare variants may reduce ND risk. This is the first demonstration that rare functional variants at a candidate locus protect against substance dependence to our knowledge, suggesting a novel mechanism of substance dependence heritability that is potentially of general importance. C1 [Xie, Pingxing; Zhao, Hongyu; Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Cosgrove, Kelly P.; Picciotto, Marina R.; Krystal, John H.; Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Krauthammer, Michael] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Xie, Pingxing; Cosgrove, Kelly P.; Krystal, John H.; Gelernter, Joel] VA Connecticut Healthcare Ctr, West Haven, CT USA. [Kranzler, Henry R.; Oslin, David] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Anton, Raymond F.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Anton, Raymond F.] Med Univ S Carolina, Dept Psychiat, Ctr Alcohol & Drug Programs, Charleston, SC 29425 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Epidemiol & Biostat, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Med, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Ophthalmol, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Genet & Genom, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. RP Gelernter, J (reprint author), Yale Univ, Sch Med, Dept Psychiat, Div Human Genet Psychiat, 950 Campbell Ave, West Haven, CT 06516 USA. EM joel.gelernter@yale.edu RI Picciotto, Marina/F-8747-2012; Cosgrove, Kelly/J-7004-2013 OI Picciotto, Marina/0000-0002-4404-1280; Farrer, Lindsay/0000-0001-5533-4225 FU National Institute of Health [R01 DA12690, R01 DA12849, R01 AA11330, R01 AA017535, K01 DA020651, R01 DA015577, 2P50-AA012870, K05 AA017435, R01 DA030976]; Vetrans Affairs (VA) VISN1 MIRECC; VA Alcohol Research Center; Clinical Neuroscience Division of the VA National Center for Posttraumatic Stress Disorder; Alkermes; GlaxoSmithKline; Gilead; Merck; ACNP Alcohol Clinical Trials Initiative (ACTIVE); Janssen Research Foundation FX This study was supported by National Institute of Health Grant Nos. R01 DA12690, R01 DA12849, R01 AA11330, R01 AA017535, K01 DA020651, R01 DA015577, 2P50-AA012870, K05 AA017435, R01 DA030976 and the Vetrans Affairs (VA) VISN1 MIRECC, VA Alcohol Research Center, and the Clinical Neuroscience Division of the VA National Center for Posttraumatic Stress Disorder. Ann Marie Lacobelle provided technical assistance. We thank the individuals and families participating in this work and the interviewers at all the participating sites for collecting the data.; Dr. Kranzler has received consulting fees from Alkermes, GlaxoSmithKline, and Gilead and research support from Merck. Dr. Anton reports being a consultant for Eli Lilly, GlaxoSmithKline, and Alkermes for the past 2 years. Drs. Kranzler and Anton also report associations with Eli Lilly, Merck, Janssen, Schering Plough, Lundbeck, Alkermes, GlaxoSmithKline, Abbott, and Johnson & Johnson; these companies provide support to the ACNP Alcohol Clinical Trials Initiative (ACTIVE) and they receive support from ACTIVE. Dr. Picciotto has received an honorarium from Targacept. Dr. Krystal reports serving as a scientific consultant and/or on the scientific advisory board to the following companies: Aisling Capital, AstraZeneca Pharmaceuticals, Brintnall & Nicolini, Easton Associates, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Lundbeck Research USA, Medivation, Merz Pharmaceuticals, MK Medical Communications, F. Hoffmann-La Roche, SK Holdings Co., Takeda Industries, Teva Pharmaceutical Industries, Abbott Laboratories, Bristol-Myers Squibb, Eisai, Eli Lilly and Co, Lohocla Research Corporation, Naurex and Pfizer Pharmaceuticals. Dr. Krystal holds less than US$ 150 in exercisable warrant options with Tetragenex Pharmaceuticals, is the principal investigator of a multicenter study in which Janssen Research Foundation has provided drug and some financial support to the Department of Veterans Affairs, and is a cosponsor for two patents under review for glutamatergic agents targeting the treatment of depression, including one that involves the antide-pressant effects of ketamine. The other authors report no biomedical financial interests or potential conflicts of interest. NR 49 TC 33 Z9 33 U1 1 U2 9 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 SEP 15 PY 2011 VL 70 IS 6 BP 528 EP 536 DI 10.1016/j.biopsych.2011.04.017 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 810UX UT WOS:000294154100007 PM 21683344 ER PT J AU Cardenas, VA Durazzo, TC Gazdzinski, S Mon, A Studholme, C Meyerhoff, DJ AF Cardenas, Valerie A. Durazzo, Timothy C. Gazdzinski, Stefan Mon, Anderson Studholme, Colin Meyerhoff, Dieter J. TI Brain Morphology at Entry into Treatment for Alcohol Dependence Is Related to Relapse Propensity SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Abstinence; deformation morphometry; longitudinal; relapse ID CHRONIC CIGARETTE-SMOKING; CONSUMPTION FOLLOWING TREATMENT; SUBSTANCE USE DISORDERS; ORBITOFRONTAL CORTEX; PROBLEM DRINKING; ADDICTION; DRUG; INDIVIDUALS; MORPHOMETRY; PREDICTORS AB Background: We examined whether any differences in brain volumes at entry into alcohol dependence treatment differentiate subsequent Abstainers from Relapsers. Methods: Individuals in alcohol dependence treatment (n = 75) underwent magnetic resonance imaging approximately 6 +/- 4 days after their last alcoholic drink, and 40 age-matched nonsmoking light drinkers (LD) were studied as control subjects. At follow-up 7.8 +/- 2.6 months later, 23 alcoholics (31%) had abstained from drinking and 52 (69%) had relapsed. Deformation morphometry compared Relapsers, Abstainers, and LD. Results: Compared with LD, future Abstainers had smaller brain tissue volumes in the left amygdala, hippocampal head, and entorhinal cortex and bilaterally in the thalamus and adjacent subcortical white matter (WM) and had larger volume in the left lateral orbitofrontal region. Compared with LD, future Relapsers had smaller brain tissue volumes in the right middle temporal, occipital, and superior frontal WM. Compared with future Abstainers, future Relapsers had smaller tissue volumes primarily in bilateral orbitofrontal cortex and surrounding WM. Results were virtually unaffected after controlling for common comorbidities. Conclusions: At entry into alcohol dependence treatment, the brain tructure of future Relapsers differs from that of future Abstainers. Future Relapsers have smaller brain volumes in regions of the mesocorticolimbic reward system that are critically involved in impulse control, emotional regulation, craving, and evaluation and anticipation of stimulus salience and hedonics. Structural abnormalities of this circuitry might confer greater risk for resumption of hazardous drinking after treatment and might contribute to the definition of a neurobiological relapse risk profile in alcohol dependence. C1 [Cardenas, Valerie A.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94121 USA. [Cardenas, Valerie A.; Durazzo, Timothy C.; Gazdzinski, Stefan; Mon, Anderson; Studholme, Colin; Meyerhoff, Dieter J.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Cardenas, VA (reprint author), San Francisco VA Med Ctr, 4150 Clement St,114M, San Francisco, CA 94121 USA. EM valerie.cardenas-nicolson@ucsf.edu FU National Institutes of Health [R01AA10788, K08DA24136, R03EB008136, P01AA11493, P41RR023953] FX This material is the result of work supported by National Institutes of Health [R01AA10788, K08DA24136, R03EB008136, P01AA11493, P41RR023953], which were administered by the Northern California Institute for Research and Education, and with resources and the use of facilities of the Veterans Affairs Medical Center, San Francisco, California. We thank Mary Rebecca Young, Bill Clift, Jeanne Eichenbaum, and Drs. Peter Banys and Ellen Herbst of the Veterans Administration Substance Abuse Day Hospital and Dr. David Pating, Karen Moise, and their colleagues at the Kaiser Permanente Chemical Dependency Recovery Program in San Francisco for their valuable assistance in recruiting participants. We also wish to extend our gratitude to the study participants, who made this research possible. NR 43 TC 34 Z9 34 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 2011 VL 70 IS 6 BP 561 EP 567 DI 10.1016/j.biopsych.2011.04.003 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 810UX UT WOS:000294154100011 PM 21601177 ER PT J AU Kuralay, F Campuzano, S Haake, DA Wang, J AF Kuralay, Filiz Campuzano, Susana Haake, David A. Wang, Joseph TI Highly sensitive disposable nucleic acid biosensors for direct bioelectronic detection in raw biological samples SO TALANTA LA English DT Article DE Screen-printed gold electrodes; Dithiols; Self-assembled monolayer; DNA hybridization; Raw samples ID SELF-ASSEMBLED MONOLAYERS; PRINTED GOLD ELECTRODES; ELECTROCHEMICAL IMPEDANCE SPECTROSCOPY; CARBON ELECTRODES; DNA MONOLAYERS; HYBRIDIZATION; MERCAPTOHEXANOL; AMPLIFICATION; GENOSENSOR; SURFACES AB The development of rapid, low-cost and reliable diagnostic methods is crucial for the identification and treatment of many diseases. Screen-printed gold electrodes (Au/SPEs), coated with a ternary monolayer interface, involving hexanedithiol (HDT), a specific thiolated capture probe (SHCP), and 6-mercapto-1 hexanol (MCH) (SHCP/HDT/MCH) are shown here to offer direct and sensitive detection of nucleic acid hybridization events in untreated raw biological samples (serum, urine and crude bacterial lysate solutions). The composition of the ternary monolayer was modified and tailored to the surface of the Au/SPE. The resulting SHCP/HDT/MCH monolayer has demonstrated to be extremely useful for enhancing the performance of disposable nucleic acid sensors based on screen-printed electrodes. Compared to common SHCP/MCH binary interfaces, the new ternary self-assembled monolayer (SAM) resulted in a 10-fold improvement in the signal (S)-to-noise (N) ratio (S/N) for 1 nM target DNA. The SHCP/HDT/MCH-modified Au/SPEs allowed the direct quantification of the target DNA down to 25 pM (0.25 fmol) and 100 pM (1 fmol) in undiluted/untreated serum and urine samples, respectively, and of 16S rRNA Escherichia coli (E. con) corresponding to 3000 CFU mu L-1 in raw cell lysate samples. The new SAM-coated screen-printed electrodes also displayed favorable non-fouling properties after a 24 h exposure to raw human serum and urine samples, offering great promise as cost-effective nucleic acid sensors for a wide range of decentralized genetic tests. (C) 2011 Elsevier B.V. All rights reserved. C1 [Kuralay, Filiz; Campuzano, Susana; Wang, Joseph] Univ Calif San Diego, Dept Nanoengn, La Jolla, CA 92093 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Wang, J (reprint author), Univ Calif San Diego, Dept Nanoengn, La Jolla, CA 92093 USA. EM josephwang@ucsd.edu RI Campuzano Ruiz, Susana/C-6448-2011; Wang, Joseph/C-6175-2011 FU National Institutes of Health [U01 AI075565]; Scientific and Technical Council of Turkey (TUBITAK); Programa Becas Complutense del Amo FX Financial support from the National Institutes of Health (Award U01 AI075565) is gratefully acknowledged. FK and SC acknowledge fellowships from The Scientific and Technical Council of Turkey (TUBITAK) and Programa Becas Complutense del Amo (2010-2011), respectively. The authors would like to acknowledge S. Marx and C. Halford for their assistance. NR 42 TC 25 Z9 26 U1 3 U2 47 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0039-9140 EI 1873-3573 J9 TALANTA JI Talanta PD SEP 15 PY 2011 VL 85 IS 3 BP 1330 EP 1337 DI 10.1016/j.talanta.2011.06.012 PG 8 WC Chemistry, Analytical SC Chemistry GA 809YO UT WOS:000294092800018 PM 21807191 ER PT J AU O'Brien, TX AF O'Brien, Terrence X. TI Iron Metabolism, Anemia, and Heart Failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE anemia; heart failure; iron ID MORTALITY C1 [O'Brien, Terrence X.] Med Univ S Carolina, Charleston, SC 29425 USA. [O'Brien, Terrence X.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP O'Brien, TX (reprint author), Med Univ S Carolina, 25 Courtenay Dr,ART 7063, Charleston, SC 29425 USA. EM obriente@musc.edu NR 11 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 13 PY 2011 VL 58 IS 12 BP 1252 EP 1253 DI 10.1016/j.jacc.2011.03.060 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 816NP UT WOS:000294609400011 PM 21903059 ER PT J AU DeSantis, SM Toole, JM Kratz, JM Uber, WE Wheat, MJ Stroud, MR Ikonomidis, JS Spinale, FG AF DeSantis, Stacia M. Toole, J. Matthew Kratz, John M. Uber, Walter E. Wheat, Margaret J. Stroud, Martha R. Ikonomidis, John S. Spinale, Francis G. TI Early Postoperative Outcomes and Blood Product Utilization in Adult Cardiac Surgery The Post-Aprotinin Era SO CIRCULATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Heart-Association CY NOV 12-16, 2010 CL Chicago, IL SP Amer Heart Assoc DE aprotinin; cardiac surgery; blood products; bleeding; postoperative outcomes ID CORONARY-ARTERY-BYPASS; RANDOMIZED CLINICAL-TRIALS; GRAFT-SURGERY; RISK; METAANALYSIS; MORTALITY; SAFETY; COHORT; PUMP AB Background-Aprotinin was a commonly used pharmacological agent for homeostasis in cardiac surgery but was discontinued, resulting in the extensive use of lysine analogues. This study tested the hypothesis that early postoperative adverse events and blood product utilization would affected in this post-aprotinin era. Methods and Results-Adult patients (n = 781) undergoing coronary artery bypass, valve replacement, or both from November 1, 2005, to October 31, 2008, at a single institution were included. Multiple logistic regression modeling and propensity scoring were performed on 29 preoperative and intraoperative variables in patients receiving aprotinin (n = 325) or lysine analogues (n = 456). The propensity-adjusted relative risk (RR) for the intraoperative use of packed red blood cells (RR, 0.75; 95% confidence interval [CI], 0.57 to 0.99), fresh frozen plasma (RR, 0.37; 95% CI, 0.21 to 0.64), and cryoprecipitate (RR: 0.06; 95% CI, 0.02 to 0.22) were lower in the aprotinin versus lysine analog group (all P < 0.05). The risk for mortality (RR, 0.53; 95% CI, 0.16 to 1.79) and neurological events (RR, 0.87; 95% CI, 0.35 to 2.18) remained similar between groups, whereas a trend for reduced risk for renal dysfunction was observed in the aprotinin group. Conclusions-In the post-aprotinin era, with the exclusive use of lysine analogues, the relative risk of early postoperative outcomes such as mortality and renal dysfunction have not improved, but the risk for the intraoperative use of blood products has increased. Thus, improvements in early postoperative outcomes have not been realized with the discontinued use of aprotinin, but rather increased blood product use has occurred with the attendant costs and risks inherent with this strategy. (Circulation. 2011; 124[suppl 1]: S62-S69.) C1 [Toole, J. Matthew; Kratz, John M.; Stroud, Martha R.; Ikonomidis, John S.; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29403 USA. [DeSantis, Stacia M.] Med Univ S Carolina, Dept Biostat & Epidemiol, Charleston, SC 29403 USA. [Uber, Walter E.; Wheat, Margaret J.] Med Univ S Carolina, Dept Pharm Serv, Charleston, SC 29403 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, 114 Doughty St, Charleston, SC 29403 USA. EM wilburnm@musc.edu FU NHLBI NIH HHS [R01 HL059165, R42 HL099258, HL59165] NR 30 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 13 PY 2011 VL 124 IS 11 SU 1 BP S62 EP S69 DI 10.1161/CIRCULATIONAHA.110.002543 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 818VB UT WOS:000294782800008 PM 21911820 ER PT J AU Dixon, JA Gorman, RC Stroud, RE Mukherjee, R Meyer, EC Baker, NL Morita, M Hamamoto, H Ryan, LP Gorman, JH Spinale, FG AF Dixon, Jennifer A. Gorman, Robert C. Stroud, Robert E. Mukherjee, Rupak Meyer, Evan C. Baker, Nathaniel L. Morita, Masato Hamamoto, Hirotsugu Ryan, Liam P. Gorman, Joseph H., III Spinale, Francis G. TI Targeted Regional Injection of Biocomposite Microspheres Alters Post-Myocardial Infarction Remodeling and Matrix Proteolytic Pathways SO CIRCULATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Heart-Association CY NOV 12-16, 2010 CL Chicago, IL SP Amer Heart Assoc DE infarct expansion; matrix metalloproteinase; tissue inhibitor of matrix metalloproteinases ID LEFT-VENTRICULAR FUNCTION; MYOCARDIAL-INFARCTION; HEART-FAILURE; CARDIAC FIBROSIS; TGF-BETA; MICRORNAS; EXPANSION; METALLOPROTEINASES; WALL; CARDIOMYOPATHY AB Background-Although localized delivery of biocomposite materials, such as calcium hydroxyapatite (CHAM), have been demonstrated to potentially attenuate adverse left ventricular (LV) remodeling after myocardial infarction (MI), the underlying biological mechanisms for this effect remain unclear. This study tested the hypothesis that targeted CHAM injections would alter proteolytic pathways (matrix metalloproteinases [MMPs] and tissue inhibitors of MMPs [TIMPs]) and would be associated with parameters of post-MI LV remodeling. Methods and Results-MI was induced in adult sheep followed by 20 targeted injections of a total volume of 1.3 mL (n = 6) or 2.6 mL of CHAM (n = 5) or saline (n = 13) and LV end-diastolic volume (EDV) and MMP/TIMP profiles in the MI region were measured at 8 weeks after MI. LV EDV decreased with 2.6 mL CHAM versus MI only (105.4 +/- 7.5 versus 80.6 +/- 4.2 respectively, P < 0.05) but not with 1.3 mL CHAM (94.5 +/- 5.0, P = 0.32). However, MI thickness increased by 2-fold in both CHAM groups compared with MI only (P < 0.05). MMP-13 increased 40-fold in the MI only group (P < 0.05) but fell by >6-fold in both CHAM groups (P < 0.05). MMP-7 increased approximately 1.5-fold in the MI only group (P < 0.05) but decreased to referent control values in both CHAM groups in the MI region (P < 0.05). Collagen content was reduced by approximately 30% in the CHAM groups compared with MI only (P < 0.05). Conclusions-Differential effects on LV remodeling and MMP/TIMP profiles occurred with CHAM. Thus, targeted injection of a biocomposite material can favorably affect the post-MI remodeling process and therefore holds promise as a treatment strategy in and of itself, or as a matrix with potentially synergistic effects with localized pharmacological or cellular therapies. (Circulation. 2011; 124[suppl 1]:S35-S45.) C1 [Dixon, Jennifer A.; Stroud, Robert E.; Mukherjee, Rupak; Meyer, Evan C.; Baker, Nathaniel L.; Spinale, Francis G.] Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Gorman, Robert C.; Morita, Masato; Hamamoto, Hirotsugu; Ryan, Liam P.; Gorman, Joseph H., III] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Gorman, Robert C.; Morita, Masato; Hamamoto, Hirotsugu; Ryan, Liam P.; Gorman, Joseph H., III] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Spinale, FG (reprint author), Strom Thurmond Res Ctr, 114 Doughty St,Suite 625, Charleston, SC 29425 USA. EM wilburnm@musc.edu FU NHLBI NIH HHS [R01 HL059165, R01 HL073021-08, R01 HL095608-03, P01 HL078825, R01 HL063954-12, R01 HL073021, R01 HL057952, HL78825, R01 HL095608, HL63954, HL95608, HL57952, HL73021, HL59165, R01 HL063954, R01 HL059165-12, R01 HL057952-12] NR 41 TC 6 Z9 6 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 13 PY 2011 VL 124 IS 11 SU 1 BP S35 EP S45 DI 10.1161/CIRCULATIONAHA.111.035774 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 818VB UT WOS:000294782800005 PM 21911817 ER PT J AU Grady, D Berkowitz, SA Katz, MH AF Grady, Deborah Berkowitz, Seth A. Katz, Mitchell H. TI Opioids for Chronic Pain SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID CHRONIC NONCANCER PAIN; THERAPY; PRESCRIPTIONS; MANAGEMENT; OVERDOSE C1 [Grady, Deborah; Berkowitz, Seth A.] Univ Calif San Francisco, Gen Internal Med Sect, San Francisco VA Med Ctr, San Francisco, CA 94115 USA. [Grady, Deborah; Berkowitz, Seth A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94115 USA. [Katz, Mitchell H.] Dept Hlth Serv, Los Angeles, CA USA. RP Grady, D (reprint author), Univ Calif San Francisco, Gen Internal Med Sect, San Francisco VA Med Ctr, 1635 Divisadero St,Ste 600, San Francisco, CA 94115 USA. OI Berkowitz, Seth/0000-0003-1030-4297 NR 14 TC 21 Z9 21 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 SEP 12 PY 2011 VL 171 IS 16 BP 1426 EP 1427 DI 10.1001/archinternmed.2011.213 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 819KY UT WOS:000294825100001 PM 21670333 ER PT J AU Steinman, MA AF Steinman, Michael A. TI Using Patients to Promote Evidence-Based Prescribing SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, 4150 Clement St,POB 181G, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu FU NIA NIH HHS [K23 AG030999] NR 7 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 12 PY 2011 VL 171 IS 16 BP 1468 EP 1469 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 819KY UT WOS:000294825100009 PM 21911630 ER PT J AU Fihn, SD Bucher, JB McDonell, M Diehr, P Rumsfeld, JS Doak, M Dougherty, C Gerrity, M Heidenreich, P Larsen, G Lee, PI Lucas, L McBryde, C Nelson, K Plomondon, ME Stadius, M Bryson, C AF Fihn, Stephan D. Bucher, Joy B. McDonell, Mary Diehr, Paula Rumsfeld, John S. Doak, Melanie Dougherty, Cynthia Gerrity, Martha Heidenreich, Paul Larsen, Greg Lee, Peter I. Lucas, Linda McBryde, Connor Nelson, Karin Plomondon, Mary E. Stadius, Michael Bryson, Christopher TI Collaborative Care Intervention for Stable Ischemic Heart Disease SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY-ARTERY-DISEASE; AMERICAN-COLLEGE; STATIN THERAPY; MANAGEMENT; HEALTH; ANGINA; POPULATION; DEPRESSION; GUIDELINES; MORTALITY AB Background: Accumulating evidence suggests that collaborative models of care enhance communication among primary care providers, improving quality of care and outcomes for patients with chronic conditions. We sought to determine whether a multifaceted intervention that used a collaborative care model and was directed through primary care providers would improve symptoms of angina, self-perceived health, and concordance with practice guidelines for managing chronic stable angina. Methods: We conducted a prospective trial, cluster randomized by provider, involving patients with symptomatic ischemic heart disease recruited from primary care clinics at 4 academically affiliated Department of Veterans Affairs health care systems. Primary end points were changes over 12 months in symptoms on the Seattle Angina Questionnaire, self-perceived health, and concordance with practice guidelines. Results: In total, 183 primary care providers and 703 patients participated in the study. Providers accepted and implemented 91.6% of 701 recommendations made by collaborative care teams. Almost half were related to medications, including adjustments to beta-blockers, long-acting nitrates, and statins. The intervention did not significantly improve symptoms of angina or selfperceived health, although end points favored collaborative care for 10 of 13 prespecified measures. While concordance with practice guidelines improved 4.5% more among patients receiving collaborative care than among those receiving usual care (P<.01), this was mainly because of increased use of diagnostic testing rather than increased use of recommended medications. Conclusion: A collaborative care intervention was well accepted by primary care providers and modestly improved receipt of guideline-concordant care but not symptoms or self-perceived health in patients with stable angina. C1 [Fihn, Stephan D.; Bucher, Joy B.; McDonell, Mary; Diehr, Paula; Dougherty, Cynthia; Nelson, Karin; Stadius, Michael; Bryson, Christopher] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98101 USA. [Fihn, Stephan D.; Nelson, Karin; Bryson, Christopher] Univ Washington, Dept Med, Seattle, WA USA. [Diehr, Paula] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Dougherty, Cynthia] Univ Washington, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. [Bucher, Joy B.] Virginia Mason Med Ctr, Dept Primary Care, Seattle, WA 98101 USA. [Rumsfeld, John S.; McBryde, Connor; Plomondon, Mary E.] Univ Colorado, VA Eastern Colorado Hlth Care Syst, Denver, CO 80202 USA. [Doak, Melanie; Gerrity, Martha; Larsen, Greg; Lucas, Linda] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. [Doak, Melanie; Gerrity, Martha; Larsen, Greg; Lucas, Linda] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Heidenreich, Paul; Lee, Peter I.] Stanford Univ, VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. [Heidenreich, Paul; Lee, Peter I.] Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. RP Fihn, SD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1100 Olive Way,Ste 1400, Seattle, WA 98101 USA. EM stephan.fihn@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [IHI 02-062, RCD 03-177] FX This work was supported by grant IHI 02-062 from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (Drs Fihn, Rumsfeld, Heidenreich, and Gerrity). Dr Bryson was supported by Career Development Award RCD 03-177 from the same funding source. NR 27 TC 17 Z9 17 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 SEP 12 PY 2011 VL 171 IS 16 BP 1471 EP 1479 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 819KY UT WOS:000294825100011 PM 21911632 ER PT J AU Funkhouser, E Levine, DA Gerald, JK Houston, TK Johnson, NK Allison, JJ Kiefe, CI AF Funkhouser, Ellen Levine, Deborah A. Gerald, Joe K. Houston, Thomas K. Johnson, Nancy K. Allison, Jeroan J. Kiefe, Catarina I. TI Recruitment activities for a nationwide, population-based, group-randomized trial: the VA MI-Plus study SO IMPLEMENTATION SCIENCE LA English DT Article ID HEALTH-SERVICES RESEARCH; CARE; PARTICIPATION; INTERVENTIONS; DESIGN; IMPACT AB Background: The Veterans Health Administration (VHA) oversees the largest integrated healthcare system in the United States. The feasibility of a large-scale, nationwide, group-randomized implementation trial of VHA outpatient practices has not been reported. We describe the recruitment and enrollment of such a trial testing a clinician-directed, Internet-delivered intervention for improving the care of postmyocardial infarction patients with multiple comorbidities. Methods: With a recruitment goal of 200 eligible community-based outpatient clinics, parent VHA facilities (medical centers) were recruited because they oversee their affiliated clinics and the research conducted there. Eligible facilities had at least four VHA-owned and -operated primary care clinics, an affiliated Institutional Review Board (IRB), and no ongoing, potentially overlapping, quality-improvement study. Between December 2003 and December 2005, in two consecutive phases, we used initial and then intensified recruitment strategies. Results: Overall, 48 of 66 (73%) eligible facilities were recruited. Of the 219 clinics and 957 clinicians associated with the 48 facilities, 168 (78%) clinics and 401 (42%) clinicians participated. The median time from initial facility contact to clinic enrollment was 222 days, which decreased by over one-third from the first to the second recruitment phase (medians: 323 and 195 days, respectively; p < .001), when more structured recruitment with physician recruiters was implemented and a dedicated IRB manager was added to the coordinating center staff. Conclusions: Large group-randomized trials benefit from having dedicated physician investigators and IRB personnel involved in recruitment. A large-scale, nationally representative, group-randomized trial of community-based clinics is feasible within the VHA or a similar national healthcare system. C1 [Funkhouser, Ellen; Johnson, Nancy K.] Birmingham VA Med Ctr, VA Res Enhancement Award Program REAP, Birmingham, AL USA. [Funkhouser, Ellen; Levine, Deborah A.] Univ Alabama, Sch Med, Dept Med, Birmingham, AL USA. [Levine, Deborah A.] Univ Michigan, Ann Arbor VA Healthcare Syst, Ann Arbor, MI 48109 USA. [Levine, Deborah A.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Levine, Deborah A.] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. [Levine, Deborah A.] Vet Affairs Hlth Serv Res & Dev Ctr Excelle, Ann Arbor, MI USA. [Gerald, Joe K.] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA. [Houston, Thomas K.; Allison, Jeroan J.; Kiefe, Catarina I.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. RP Funkhouser, E (reprint author), Birmingham VA Med Ctr, VA Res Enhancement Award Program REAP, Birmingham, AL USA. EM emfunk@uab.edu RI Houston, Thomas/F-2469-2013 OI Allison, Jeroan/0000-0003-4472-2112 FU VA Health Services Research and Development (HSRD) [SDR 03-090-1]; National Heart, Lung, and Blood Institute [R01 HL70786] FX This project was funded in part by grant SDR 03-090-1 from the VA Health Services Research and Development (HSR&D) and by grant number R01 HL70786 from the National Heart, Lung, and Blood Institute. NR 30 TC 2 Z9 2 U1 0 U2 1 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 SEP 9 PY 2011 VL 6 AR 105 DI 10.1186/1748-5908-6-105 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 828AO UT WOS:000295472800001 PM 21906278 ER PT J AU Stefan, M Jacobson, EM Huber, AK Greenberg, DA Li, CW Skrabanek, L Conception, E Fadlalla, M Ho, K Tomer, Y AF Stefan, Mihaela Jacobson, Eric M. Huber, Amanda K. Greenberg, David A. Li, Cheuk Wun Skrabanek, Luce Conception, Erlinda Fadlalla, Mohammed Ho, Kenneth Tomer, Yaron TI Novel Variant of Thyroglobulin Promoter Triggers Thyroid Autoimmunity through an Epigenetic Interferon alpha-modulated Mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN GENOME; HASHIMOTOS-THYROIDITIS; SUSCEPTIBILITY GENE; LINKAGE ANALYSIS; DISEASE; TRANSCRIPTION; ASSOCIATION; GRAVES; IDENTIFICATION; METHYLATIONS AB Autoimmune thyroid diseases (AITD) arise from complex interactions between genetic, epigenetic, and environmental factors. Whole genome linkage scans and association studies have established thyroglobulin (TG) as a major AITD susceptibility gene. However, the causative TG variants and the pathogenic mechanisms are unknown. Here, we describe a genetic/epigenetic mechanism by which a newly identified TG promoter single-nucleotide polymorphism (SNP) variant predisposes to AITD. Sequencing analyses followed by case control and family-based association studies identified an SNP (-1623A -> G) that was associated with AITD in the Caucasian population (p = 0.006). We show that the nucleotide substitution introduced by SNP (-1623A/G) modified a binding site for interferon regulatory factor-1 (IRF-1), a major interferon-induced transcription factor. Using chromatin immunoprecipitation, we demonstrated that IRF-1 binds to the 5' TG promoter motif, and the transcription factor binding correlates with active chromatin structure and is marked by enrichment of mono-methylated Lys-4 residue of histone H3, a signature of active transcriptional enhancers. Using reporter mutations and siRNA approaches, we demonstrate that the disease-associated allele (G) conferred increased TG promoter activity through IRF-1 binding. Finally, treatment of thyroid cells with interferon alpha, a known trigger of AITD, increased TG promoter activity only when it interacted with the disease-associated variant through IRF-1 binding. These results reveal a new mechanism of interaction between environmental (IFN alpha) and genetic (TG) factors to trigger AITD. C1 [Stefan, Mihaela; Huber, Amanda K.; Conception, Erlinda; Ho, Kenneth; Tomer, Yaron] Mt Sinai Med Ctr, Dept Med, Div Endocrinol, New York, NY 10029 USA. [Jacobson, Eric M.; Li, Cheuk Wun; Fadlalla, Mohammed] Univ Cincinnati, Div Endocrinol, Cincinnati, OH 45267 USA. [Greenberg, David A.] Columbia Univ, Div Stat Genet, New York, NY 10032 USA. [Skrabanek, Luce] Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA. [Skrabanek, Luce] Cornell Univ, Weill Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10021 USA. [Stefan, Mihaela; Tomer, Yaron] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Stefan, M (reprint author), Mt Sinai Med Ctr, Dept Med, Div Endocrinol, New York, NY 10029 USA. EM mihaela.stefan@mssm.edu; yaron.tomer@mssm.edu FU National Institutes of Health [DK61659, DK067555, DK073681, MH48858, NS27941]; Veterans Affairs merit award; American Thyroid Association FX This work was supported, in whole or in part, by National Institutes of Health Grants DK61659, DK067555, and DK073681 (to Y. T.) and Grants MH48858 and NS27941 (to D. A. G.). This work was also supported by a Veterans Affairs merit award (to Y. T.).; Supported by a grant from the American Thyroid Association. NR 50 TC 24 Z9 25 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 SEP 9 PY 2011 VL 286 IS 36 BP 31168 EP 31179 DI 10.1074/jbc.M111.247510 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 814WI UT WOS:000294487500012 PM 21757724 ER PT J AU Dhaliwal, G AF Dhaliwal, Gurpreet TI The Mechanics of Reasoning SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. RP Dhaliwal, G (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM gurpreet.dhaliwal@ucsf.edu NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 7 PY 2011 VL 306 IS 9 BP 918 EP 919 DI 10.1001/jama.2011.1027 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 815QT UT WOS:000294542600001 PM 21900128 ER PT J AU van Ryn, M Saha, S AF van Ryn, Michelle Saha, Somnath TI Exploring Unconscious Bias in Disparities Research and Medical Education SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HEALTH-CARE; PROVIDERS; CONTRIBUTE C1 [van Ryn, Michelle] Univ Minnesota, Sch Med, Dept Family Med & Community Hlth, Minneapolis, MN 55414 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. RP van Ryn, M (reprint author), Univ Minnesota, Sch Med, Dept Family Med & Community Hlth, 925 SE Delaware St,Ste 221, Minneapolis, MN 55414 USA. EM vanry001@umn.edu FU NHLBI NIH HHS [R01 HL085631] NR 14 TC 19 Z9 19 U1 2 U2 11 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 SEP 7 PY 2011 VL 306 IS 9 BP 995 EP 996 DI 10.1001/jama.2011.1275 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 815QT UT WOS:000294542600020 PM 21900142 ER PT J AU Ku, TNK Naseri, A Han, Y Porco, TC Rutar, T AF Ku, Tina K. Naseri, Ayman Han, Ying Porco, Travis C. Rutar, Tina TI Effect of Timing and Duration of Tamsulosin Exposure on Complications in Resident-Performed Phacoemulsification SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article ID FLOPPY-IRIS-SYNDROME; BENIGN PROSTATIC HYPERTROPHY; CATARACT-SURGERY; CLINICAL FINDINGS; LEARNING-CURVE; IFIS; ASSOCIATION; EPINEPHRINE; PROPHYLAXIS; MANAGEMENT AB BACKGROUND AND OBJECTIVES: Tamsulosin can cause intraoperative floppy iris syndrome and increase the risk of phacoemulsification complications. This study evaluated whether the risk of complications was associated with the timing or duration of preoperative tamsulosin exposure. PATIENTS AND METHODS: The current study was a retrospective review of electronic medical records of resident-performed phacoemulsification surgeries from 1998 to 2008 at a Veterans Administration Hospital. There were 73 eyes with recent tamsulosin exposure (within 30 days preoperatively) and 28 eyes with remote exposure (> 30 days preoperatively but within 3 years of surgery). RESULTS: There was a trend toward more total complications in recent compared with remote tamsulosin exposure cases (31.5% vs 14.3%, P = .09). A longer duration of tamsulosin use was not statistically associated with an increased risk of total complications. CONCLUSION: The authors were unable to detect a statistically significant effect of duration of tamsulosin use on the risk of intraoperative complications in phacoemulsification surgery. C1 [Ku, Tina K.; Naseri, Ayman; Han, Ying; Porco, Travis C.; Rutar, Tina] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Naseri, Ayman; Porco, Travis C.] Francis I Proctor Fdn Res Ophthalmol, San Francisco, CA USA. [Naseri, Ayman] San Francisco VA Med Ctr, Dept Ophthalmol, San Francisco, CA USA. [Porco, Travis C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Div Prevent Med & Publ Hlth, San Francisco, CA 94143 USA. RP Rutar, T (reprint author), Univ Calif San Francisco, Dept Ophthalmol, 10 Koret Way,K301, San Francisco, CA 94143 USA. EM rutart@vision.ucsf.edu FU Research to Prevent Blindness, New York, New York; University of California, Bethesda, Maryland [NIH P30] FX Supported in part by an unrestricted grant from Research to Prevent Blindness, New York, New York, and by the University of California Institutional Core Grant For Vision Research (NIH P30), Bethesda, Maryland. NR 33 TC 1 Z9 2 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1542-8877 J9 OPHTHAL SURG LAS IM JI Ophthalmic Surg. Lasers Imaging PD SEP-OCT PY 2011 VL 42 IS 5 BP 416 EP 422 DI 10.3928/15428877-20110602-01 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 959UX UT WOS:000305342100009 PM 21661666 ER PT J AU Impink, BG Collinger, JL Boninger, ML AF Impink, Bradley G. Collinger, Jennifer L. Boninger, Michael L. TI The Effect of Symptoms of Carpal Tunnel Syndrome on Ultrasonographic Median Nerve Measures Before and After Wheelchair Propulsion SO PM&R LA English DT Article ID CROSS-SECTIONAL AREA; BODY-MASS INDEX; HIGH-RESOLUTION SONOGRAPHY; UPPER EXTREMITY; CLINICAL IMPLICATIONS; PARAPLEGIC PATIENTS; GENERAL-POPULATION; FUNCTIONAL STATUS; CANAL PRESSURE; DIAGNOSIS AB Objective: To quantify median nerve characteristics before and after strenuous wheelchair propulsion and relate them to symptoms of carpal tunnel syndrome (CTS). We hypothesized that persons with and without symptoms of CTS would have significantly different nerve characteristics at baseline and after propulsion. Design: A repeated-measures design was used to obtain ultrasound images of the median nerve at 3 levels of the wrist (radius, pisiform, and hamate) before and after wheelchair propulsion. Investigators were blinded to subject history related to CTS. Setting: The 2007 and 2008 National Veterans Wheelchair Games and the Human Engineering Research Laboratories. Participants: Fifty-four participants between the ages of 18 and 65 years with a nonprogressive disability who used a manual wheelchair as their primary means of mobility completed this study. Methods: Participants completed questionnaires regarding demographics and the presence and severity of symptoms of CTS. Ultrasound images of the median nerve were obtained before and after a 15-minute strenuous wheelchair-propulsion task. Main Outcome Measurements: Baseline values and post-propulsion changes were determined for median nerve cross-sectional area, flattening ratio, and swelling ratio. Differences in median nerve variables between symptomatic and asymptomatic groups were assessed. Results: No significant differences between symptom groups were identified at baseline; however, persons with symptoms of CTS showed a significantly different percent change from baseline compared with the asymptomatic participants for cross-sectional area at pisiform (P = .014) and flattening ratio at hamate (P = .022), and they showed a strong trend toward a difference in swelling ratio (P = .0502). For each of these variables, the change in the symptomatic group was in the opposite direction of the change in the asymptomatic group. Conclusions: We found several median nerve responses to wheelchair propulsion associated with symptoms of CTS. These responses occurred even though no baseline ultrasound difference was found based on symptoms. Future research is necessary to determine how propulsion characteristics (ie, force, repetition, and posture) affect the median nerve response. PM R 2011;3:803-810 C1 [Impink, Bradley G.; Collinger, Jennifer L.; Boninger, Michael L.] Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. [Impink, Bradley G.; Collinger, Jennifer L.; Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Collinger, Jennifer L.; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Boninger, ML (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, 7180 Highland Dr,151R1-H,Bldg 4,East Wing, Pittsburgh, PA 15206 USA. EM boninger@pitt.edu OI Boninger, Michael/0000-0001-6966-919X FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development [B3142C]; National Institute on Disability and Rehabilitation Research [H133E070024]; National Institutes of Health [R21HD054529]; National Science Foundation [DGE0333420] FX This material is based on work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development (B3142C), the National Institute on Disability and Rehabilitation Research (H133E070024), the National Institutes of Health (R21HD054529), and the National Science Foundation (DGE0333420). The findings presented are the result of work supported with resources and the use of facilities of 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 55 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 1934-1482 J9 PM&R JI PM&R PD SEP PY 2011 VL 3 IS 9 BP 803 EP 810 DI 10.1016/j.pmrj.2011.04.009 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 961BE UT WOS:000305438100004 PM 21944298 ER PT J AU Akiyoshi, K Dziennis, S Palmateer, J Ren, XF Vandenbark, AA Offner, H Herson, PS Hurn, PD AF Akiyoshi, Kozaburo Dziennis, Suzan Palmateer, Julie Ren, Xuefang Vandenbark, Arthur A. Offner, Halina Herson, Paco S. Hurn, Patricia D. TI Recombinant T Cell Receptor Ligands Improve Outcome After Experimental Cerebral Ischemia SO TRANSLATIONAL STROKE RESEARCH LA English DT Article DE Cerebral ischemia; Cerebral infarction; Inflammation; T lymphocyte; Immunotherapy; Mouse; Middle cerebral artery occlusion; Stroke ID EXPERIMENTAL STROKE; MULTIPLE-SCLEROSIS; INFARCT VOLUME; MICE; ASSOCIATION; ARTHRITIS; SEVERITY AB A key target for novel stroke therapy is the regulation of post-ischemic inflammatory mechanisms. Recent evidence emphasizes the role of T lymphocytes of differing subtypes in the evolution is ischemic brain damage. We have recently demonstrated the benefit of myelin antigen-specific immunodulatory agents known as recombinant T cell receptor ligands (RTLs) in a standard murine model of focal stroke. The aim of the current study was to extend this initial observation to RTL treatment in a therapeutically relevant timing after middle cerebral artery occlusion (MCAO) and verify functional benefit to complement histological outcome measures. We observed that the administration of mouse-specific RTL551 reduced infarct size and improved sensorimotor outcome when administered within a 3 h post-ischemic therapeutic window. RTL551 treatment reduced cortical, caudate putamen, and total infarct volume as compared to vehicle-treated mice. Using a standard behavioral testing repertoire, we observed that RTL551 reduced sensorimotor impairment 3 days after MCAO. Humanized RTL1000 (HLA-DR2 moiety linked to hMOG-35-55 peptide) also reduced infarct size in HLA-DR2 transgenic mice. These data indicate that this neuroantigen-specific immunomodulatory agent reduces damage when administered in a therapeutically relevant reperfusion timeframe. C1 [Akiyoshi, Kozaburo; Dziennis, Suzan; Palmateer, Julie; Ren, Xuefang; Offner, Halina; Herson, Paco S.; Hurn, Patricia D.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. [Dziennis, Suzan; Ren, Xuefang; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Portland, OR 97239 USA. [Vandenbark, Arthur A.] Dept Vet Affairs Med Ctr, Res Serv, Portland, OR 97239 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Vandenbark, Arthur A.; Offner, Halina; Hurn, Patricia D.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. RP Herson, PS (reprint author), Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM hersonp@ohsu.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX The authors thank Ms. Kathy Gage, grants and publications writer for the Department of Anesthesiology and Perioperative Medicine, OHSU, for her outstanding editorial work in the preparation of this paper. This material is 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. The contents do not represent the views of the Department of Veterans Affairs or the US government. NR 23 TC 12 Z9 12 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-4483 EI 1868-601X J9 TRANSL STROKE RES JI Transl. Stroke Res. PD SEP PY 2011 VL 2 IS 3 BP 404 EP 410 DI 10.1007/s12975-011-0085-1 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 943YH UT WOS:000304163500021 PM 21961027 ER PT J AU Mendez, MF AF Mendez, Mario F. TI Malapropisms, or "The Archie Bunker Syndrome," and Frontotemporal Dementia SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Letter C1 [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Ctr, Dept Neurol, Los Angeles, CA 90095 USA. [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Ctr, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Mendez, MF (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Ctr, Dept Neurol, Los Angeles, CA 90095 USA. EM mmendez@UCLA.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2011 VL 23 IS 4 BP E3 EP E3 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 924XS UT WOS:000302725200003 ER PT J AU Kunik, M AF Kunik, Mark TI CBT for older adults with chronic medical illnesses and psychological comorbidity SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Meeting Abstract C1 [Kunik, Mark] Houston Vet Affairs Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD SEP PY 2011 VL 23 SU 1 BP S68 EP S69 PG 2 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 889UX UT WOS:000300101100114 ER PT J AU Mintzer, J Brawman-Mintzer, O Nietert, P Vankirk, K Longmire, CF Jones, E Stuckey, M AF Mintzer, Jacobo Brawman-Mintzer, O. Nietert, P. Vankirk, K. Longmire, C. Flynn Jones, E. Stuckey, M. TI Escitalopram in the treatment of non-depressed elderly patients with generalized anxiety disorder SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Meeting Abstract ID CONTROLLED-TRIAL C1 [Mintzer, Jacobo; Brawman-Mintzer, O.; Nietert, P.; Jones, E.; Stuckey, M.] Ralph Johnson VA Med Ctr, N Charleston, SC USA. [Mintzer, Jacobo; Brawman-Mintzer, O.; Nietert, P.; Vankirk, K.; Longmire, C. Flynn] Med Univ S Carolina, N Charleston, SC USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD SEP PY 2011 VL 23 SU 1 BP S305 EP S306 PG 2 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 889UX UT WOS:000300101100410 ER PT J AU Kraker, J Zivkovic, SA AF Kraker, Jessica Zivkovic, Sasa A. TI Autoimmune Neuromuscular Disorders SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE Autoimmune; neuromuscular; neuropathy; myositis; myasthenia gravis; treatment ID INFLAMMATORY-DEMYELINATING POLYNEUROPATHY; EATON-MYASTHENIC-SYNDROME; GUILLAIN-BARRE-SYNDROME; QUALITY STANDARDS SUBCOMMITTEE; MULTIFOCAL MOTOR NEUROPATHY; LONG-TERM PROGNOSIS; FOLLOW-UP; MONOCLONAL GAMMOPATHY; PLASMA-EXCHANGE; UNDETERMINED SIGNIFICANCE AB Autoimmune neuromuscular disorders affecting peripheral nerves, neuromuscular junction or muscle have a wide clinical spectrum with diverse pathogenetic mechanisms. Peripheral nervous system may be targeted in the context of complex immune reactions involving different cytokines, antigen-presenting cells, B cells and different types of T cells. Various immunomodulating and cytotoxic treatments block proliferation or activation of immune cells by different mechanisms attempting to control the response of the immune system and limit target organ injury. Most treatment protocols for autoimmune neuromuscular disorders are based on the use of corticosteroids, intravenous immunoglobulins and plasmapheresis, with cytotoxic agents mostly used as steroid-sparing medications. More recently, development of specific monoclonal antibodies targeting individual cell types allowed a different approach targeting specific immune pathways, but these new treatments are also associated with various adverse effects and their long-term efficacy is still unknown. C1 [Kraker, Jessica; Zivkovic, Sasa A.] Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA 15213 USA. [Zivkovic, Sasa A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zivkovic, SA (reprint author), Univ Pittsburgh, Med Ctr, Dept Neurol, 200 Lothrop St,PUH F878, Pittsburgh, PA 15213 USA. EM zivkovics@upmc.edu NR 71 TC 1 Z9 1 U1 1 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD SEP PY 2011 VL 9 IS 3 BP 400 EP 408 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 883HF UT WOS:000299624100002 PM 22379454 ER PT J AU Felts, AS Bates, BS Rodriguez, AL Menon, UN Jadhav, S Blobaum, AL Byers, FW Daniels, JS Lawson, KP Jones, CK Conn, PJ Lindsley, CW Emmitte, KA AF Felts, A. S. Bates, B. S. Rodriguez, A. L. Menon, U. N. Jadhav, S. Blobaum, A. L. Byers, F. W. Daniels, J. S. Lawson, K. P. Jones, C. K. Conn, P. J. Lindsley, C. W. Emmitte, K. A. TI SAR and in vitro/vivo Evaluation of a Novel Series of Substituted Aryl Ether Benzamides as Negative Allosteric Modulators of mGlu(5) SO CURRENT NEUROPHARMACOLOGY LA English DT Meeting Abstract C1 [Felts, A. S.; Bates, B. S.; Rodriguez, A. L.; Menon, U. N.; Jadhav, S.; Blobaum, A. L.; Byers, F. W.; Daniels, J. S.; Jones, C. K.; Conn, P. J.; Lindsley, C. W.; Emmitte, K. A.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Felts, A. S.; Bates, B. S.; Rodriguez, A. L.; Menon, U. N.; Jadhav, S.; Blobaum, A. L.; Byers, F. W.; Daniels, J. S.; Jones, C. K.; Conn, P. J.; Lindsley, C. W.; Emmitte, K. A.] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA. [Jones, C. K.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN USA. Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA. RI Conn, Peter/D-7848-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD SEP PY 2011 VL 9 SU 1 MA 55 BP 20 EP 20 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 883IJ UT WOS:000299627200056 ER PT J AU Niswender, CM Jones, CK Hopkins, CR Thompson, AD Bubser, M Engers, D Gogliotti, RD Blobaum, AL Salovich, JM Cheung, YY Morrison, RD Dawson, ES Zamorano, R Brewer, KA Daniels, JS Lindsley, CW Conn, PJ AF Niswender, C. M. Jones, C. K. Hopkins, C. R. Thompson, A. D. Bubser, M. Engers, D. Gogliotti, R. D. Blobaum, A. L. Salovich, J. M. Cheung, Y. Y. Morrison, R. D. Dawson, E. S. Zamorano, R. Brewer, K. A. Daniels, J. S. Lindsley, C. W. Conn, P. J. TI mGlu4 Receptor Positive Allosteric Modulator Development for the Treatment of CNS Disorders SO CURRENT NEUROPHARMACOLOGY LA English DT Meeting Abstract C1 [Niswender, C. M.; Jones, C. K.; Hopkins, C. R.; Thompson, A. D.; Bubser, M.; Engers, D.; Gogliotti, R. D.; Blobaum, A. L.; Salovich, J. M.; Cheung, Y. Y.; Morrison, R. D.; Dawson, E. S.; Zamorano, R.; Brewer, K. A.; Daniels, J. S.; Lindsley, C. W.; Conn, P. J.] Vanderbilt Univ, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37212 USA. [Niswender, C. M.; Jones, C. K.; Hopkins, C. R.; Thompson, A. D.; Bubser, M.; Engers, D.; Gogliotti, R. D.; Blobaum, A. L.; Salovich, J. M.; Cheung, Y. Y.; Morrison, R. D.; Dawson, E. S.; Zamorano, R.; Brewer, K. A.; Daniels, J. S.; Lindsley, C. W.; Conn, P. J.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37212 USA. [Hopkins, C. R.; Lindsley, C. W.] Vanderbilt Univ, Dept Chem, Nashville, TN 37212 USA. [Jones, C. K.] Vanderbilt Univ, US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. [Lindsley, C. W.] Vanderbilt Univ, Vanderbilt Inst Chem Biol, Nashville, TN 37212 USA. RI Conn, Peter/D-7848-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD SEP PY 2011 VL 9 SU 1 MA 131 BP 48 EP 48 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 883IJ UT WOS:000299627200131 ER PT J AU Welsh, CA Flanagan, ME Kiess, C Doebbeling, BN AF Welsh, Catherine Amber Flanagan, Mindy E. Kiess, Chris Doebbeling, Bradley N. TI Implementing the MRSA Bundle in ICUs: One Citywide Collaborative's Key Lessons Learned SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID HEALTH-CARE; INNOVATIONS AB Because bundle implementation in intensive care units to reduce methicillin-resistant Staphylococcus aureus is challenging, we conducted in-depth interviews with implementation teams at 5 participating hospitals. Key lessons learned across hospitals included the following: maintain management support, engage frontline staff, build the right multidisciplinary team, conduct process mapping, and commit to data collection and feedback. Infect Control Hosp Epidemiol 2011;32(9):918-921 C1 [Welsh, Catherine Amber; Flanagan, Mindy E.; Doebbeling, Bradley N.] Indiana Univ, Ctr Hlth Serv & Outcomes Res, Indianapolis, IN 46204 USA. [Welsh, Catherine Amber] IU Purdue Univ Indianapolis, Sch Engn & Technol, Indianapolis, IN USA. [Kiess, Chris; Doebbeling, Bradley N.] Regenstrief Inst Hlth Care, Indianapolis, IN USA. [Doebbeling, Bradley N.] US Dept Vet Affairs, Hlth Serv Res & Dev Serv, Ctr Excellence, Indianapolis, IN USA. [Doebbeling, Bradley N.] IU Sch Med, Dept Med, Indianapolis, IN USA. RP Welsh, CA (reprint author), 799 W Michigan St, Indianapolis, IN 46202 USA. EM amwelsh@hotmail.com FU US Agency for Healthcare Research and Quality under Office of Management and Budget [HHSA2902006000131] FX US Agency for Healthcare Research and Quality (contract HHSA2902006000131, under Office of Management and Budget control no. 0935-0168, expiration date September 30, 2012). NR 7 TC 4 Z9 4 U1 0 U2 0 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 SEP PY 2011 VL 32 IS 9 BP 918 EP 921 DI 10.1086/661101 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 876BW UT WOS:000299083000014 PM 21828975 ER PT J AU Rokkam, D LaFemina, MJ Lee, JW Matthay, MA Frank, JA AF Rokkam, Deepti LaFemina, Michael J. Lee, Jae Woo Matthay, Michael A. Frank, James A. TI Claudin-4 Levels Are Associated with Intact Alveolar Fluid Clearance in Human Lungs SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; JUNCTION FIBRIL ARCHITECTURE; EPITHELIAL BARRIER FUNCTION; PERFUSED HUMAN LUNGS; CHARGE SELECTIVITY; EXPRESSION; INJURY; CELLS; PERMEABILITY; RESISTANCE AB The removal of edema from the air spaces is a critical function of the alveolar barrier requiring intact tight junctions. Alveolar fluid clearance contributes to graft function after transplantation and is associated with survival in patients with acute lung injury. Claudin-4 concentrations are known to increase during lung injury and the loss of claudin-4 decreases alveolar fluid clearance in mice. This study was therefore undertaken to evaluate whether differences in lung expression of the tight junction protein claudin-4 are associated with alveolar fluid clearance or clinical measures of lung function. Alveolar fluid clearance rates were measured in ex vivo perfused human lungs not used for transplantation and were compared with histological lung injury and clinical measures of lung injury in the donors. Claudin-4 staining demonstrated a positive correlation with alveolar fluid clearance (Spearman rank correlation [r(s)] = 0.71; P < 0.003); however, claudin-4 staining was not strongly associated with histological measures of lung injury. The expression of other tight junction proteins (including ZO-1) was not associated with alveolar fluid clearance or claudin-4 levels. Claudin-4 staining was lower in lungs from donors with greater impairment in respiratory physiology. These data suggest that claudin-4 may promote alveolar fluid clearance and demonstrate that the amount of claudin-4 expressed may provide specific information regarding alveolar epithelial barrier function that strengthens the link between histological changes and physiological impairment. (Am J Pathol 2011, 179:1081-1087; DOI: 10.1016/j.ajpath.2011.05.017) C1 [Frank, James A.] Univ Calif San Francisco, Cardiovasc Res Inst, No Calif Inst Res & Educ, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Frank, JA (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, No Calif Inst Res & Educ, San Francisco VA Med Ctr, 4150 Clement St,Box 111D, San Francisco, CA 94121 USA. EM james.frank@ucsf.edu FU National Institutes of Health [HL88440]; National Heart, Lung and Blood Institute [HL551856] FX Supported by grants from the National Institutes of Health (HL88440 to J.A.F.) and the National Heart, Lung and Blood Institute (HL551856 to J.A.F. and M.A.M.). NR 28 TC 31 Z9 31 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2011 VL 179 IS 3 BP 1081 EP 1087 DI 10.1016/j.ajpath.2011.05.017 PG 7 WC Pathology SC Pathology GA 865JN UT WOS:000298307300002 PM 21741940 ER PT J AU Beadling, C Heinrich, MC Warrick, A Forbes, EM Nelson, D Justusson, E Levine, J Neff, TL Patterson, J Presnell, A McKinley, A Winter, LJ Dewey, C Harlow, A Barney, O Druker, BJ Schuff, KG Corless, CL AF Beadling, Carol Heinrich, Michael C. Warrick, Andrea Forbes, Erin M. Nelson, Dylan Justusson, Emily Levine, Judith Neff, Tanaya L. Patterson, Janice Presnell, Ajia McKinley, Arin Winter, Laura J. Dewey, Christie Harlow, Amy Barney, Oscar Druker, Brian J. Schuff, Kathryn G. Corless, Christopher L. TI Multiplex Mutation Screening by Mass Spectrometry Evaluation of 820 Cases from a Personalized Cancer Medicine Registry SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID CELL LUNG-CANCER; METASTATIC COLORECTAL-CANCER; CHRONIC MYELOID-LEUKEMIA; GROWTH-FACTOR RECEPTOR; ABL TYROSINE KINASE; BRAF MUTATIONS; IMATINIB MESYLATE; BETA-CATENIN; PHILADELPHIA-CHROMOSOME; ENDOMETRIAL CARCINOMAS AB There is an immediate and critical need for a rapid, broad-based genotyping method that can evaluate multiple mutations simultaneously in clinical cancer specimens and identify patients most likely to benefit from targeted agents now in use or in late-stage clinical development. We have implemented a prospective genotyping approach to characterize the frequency and spectrum of mutations amenable to drug targeting present in urothelial, colorectal, endometrioid, and thyroid carcinomas and in melanoma. Cancer patients were enrolled in a Personalized Cancer Medicine Registry that houses both clinical information and genotyping data, and mutation screening was performed using a multiplexed assay panel with mass spectrometry based analysis to detect 390 mutations across 30 cancer genes. Formalin fixed, paraffin-embedded specimens were evaluated from 820 Registry patients. The genes most frequently mutated across multiple cancer types were BRAF, PIK3C4, KRAS, and NRAS. Less common mutations were also observed in AKT1, CTNNB1, FGFR2, FGFR3, GNAQ, HRAS, and MAP2K1. Notably, 48 of 77 PIK3C4-mutant cases (62%) harbored at least one additional mutation in another gene, most often KRAS. Among melanomas, only 54 of 73 BRAF mutations (74%) were the V600E substitution. These findings demonstrate the diversity and complexity of mutations in druggable targets among the different cancer types and underscore the need for a broad-spectrum, prospective genotyping approach to personalized cancer medicine. (J Mol Diagn 2011, 13: 504-513; DOI: 10.1016/j.jmoldx.2011.04.003) C1 [Corless, Christopher L.] OHSU, Dept Pathol, Knight Canc Inst, Portland, OR 97239 USA. [Beadling, Carol; Heinrich, Michael C.] OHSU, Div Hematol Oncol, Portland, OR 97239 USA. [Schuff, Kathryn G.] OHSU, Div Endocrinol, Portland, OR 97239 USA. [Corless, Christopher L.] Portland VA Med Ctr, Portland, OR USA. RP Corless, CL (reprint author), OHSU, Dept Pathol, Knight Canc Inst, Mailcode L471,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM corlessc@ohsu.edu OI Patterson, Janice/0000-0002-8969-2933 FU Novartis Pharmaceuticals FX This study was supported in part with funding from Novartis Pharmaceuticals. NR 65 TC 55 Z9 55 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD SEP PY 2011 VL 13 IS 5 BP 504 EP 513 DI 10.1016/j.jmoldx.2011.04.003 PG 10 WC Pathology SC Pathology GA 865JG UT WOS:000298306600006 PM 21726664 ER PT J AU Hurley, RA Filley, CM Taber, KH AF Hurley, Robin A. Filley, Christopher M. Taber, Katherine H. TI Central Pontine Myelinolysis: A Metabolic Disorder of Myelin SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Editorial Material ID OSMOTIC DEMYELINATION SYNDROME; MAGNETIC-RESONANCE-SPECTROSCOPY; EXTRAPONTINE MYELINOLYSIS; DIFFUSION; PATIENT; HYPONATREMIA; MANIFESTATIONS; PLASMAPHERESIS; COMPLICATION; ALCOHOLISM C1 [Hurley, Robin A.; Taber, Katherine H.] WG Hefner Vet Affairs Med Ctr, Vet Affairs Midatlantic Mental Illness Res Educ &, Salisbury, NC 28144 USA. [Hurley, Robin A.; Taber, Katherine H.] WG Hefner Vet Affairs Med Ctr, Res & Educ Serv Line, Salisbury, NC USA. [Hurley, Robin A.] Wake Forest Univ, Bowman Gray Sch Med, Dept Psychiat, Winston Salem, NC USA. [Hurley, Robin A.] Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC USA. [Hurley, Robin A.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Filley, Christopher M.] Univ Colorado, Sch Med, Behav Sect, Denver, CO USA. [Filley, Christopher M.] Denver Vet Affairs Med Ctr, Neurol Serv, Denver, CO USA. [Taber, Katherine H.] Edward Via Coll Osteopath Med, Div Biomed Sci, Blacksburg, VA USA. [Taber, Katherine H.] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. RP Hurley, RA (reprint author), Hefner VA Med Ctr, Salisbury, NC 28144 USA. EM Robin.Hurley@va.gov NR 56 TC 0 Z9 0 U1 0 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2011 VL 23 IS 4 BP IV EP 374 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 875GT UT WOS:000299019100001 ER PT J AU Wagner, PJ Wortzel, HS Frey, KL Anderson, CA Arciniegas, DB AF Wagner, Peter J. Wortzel, Hal S. Frey, Kimberly L. Anderson, C. Alan Arciniegas, David B. TI Clock-Drawing Performance Predicts Inpatient Rehabilitation Outcomes After Traumatic Brain Injury SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID POSTTRAUMATIC AMNESIA; PRACTICAL SCALE; SEVERITY; MODERATE; BATTERY AB The authors used clock-drawing performance to assess cognition and predict inpatient rehabilitation outcomes among persons with traumatic brain injury. Clock-drawing performance, as assessed with the Clock Drawing Interpretation Scale, predicts rehabilitation length of stay as well as Functional Independence Measure scores at the time of neurobehavioral assessment and rehabilitation discharge. (The Journal of Neuropsychiatry and Clinical Neurosciences 2011; 23:449-453) C1 [Wagner, Peter J.; Wortzel, Hal S.; Frey, Kimberly L.; Anderson, C. Alan; Arciniegas, David B.] Univ Colorado, Sch Med, Dept Psychiat, Neurobehav Disorders Program, Aurora, CO 80045 USA. [Wortzel, Hal S.] Denver Vet Affairs Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 19, Denver, CO USA. [Anderson, C. Alan; Arciniegas, David B.] Univ Colorado, Sch Med, Dept Neurol, Behav Neurol Sect, Aurora, CO USA. [Anderson, C. Alan] Denver Vet Affairs Med Ctr, Neurol Serv, Denver, CO USA. RP Arciniegas, DB (reprint author), Univ Colorado, Sch Med, Dept Psychiat, Neurobehav Disorders Program, Aurora, CO 80045 USA. EM David.Arciniegas@UCDenver.edu FU HCA/HealthONE Spalding Rehabilitation Hospital; VA VISN-19 Mental Illness Research, Education, and Clinical Center FX This work was supported in part by HCA/HealthONE Spalding Rehabilitation Hospital and the VA VISN-19 Mental Illness Research, Education, and Clinical Center. NR 17 TC 5 Z9 5 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2011 VL 23 IS 4 BP 449 EP 453 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 875GT UT WOS:000299019100012 PM 22231317 ER PT J AU Spigner, C Lyles, CR Galvin, G Sabin, J Davis, C Dick, A Young, BA AF Spigner, Clarence Lyles, Courtney Rees Galvin, Georgia Sabin, Janice Davis, Connie Dick, Andre Young, Bessie A. TI A Qualitative Assessment of Personal and Social Responsibility for Kidney Disease: The Increasing Kidney Disease Awareness Network Transplant Project SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE kidney; transplant; race/ethnicity; physicians; patient self-management; qualitative research ID STAGE RENAL-DISEASE; SICK ROLE; ETHNIC-DIFFERENCES; PUBLIC-HEALTH; UNITED-STATES; POPULATION; CARE; END; RACE; DISPARITIES AB Introduction: Limited qualitative research has explored opinions of kidney disease health care providers regarding racial and ethnic disparities in access to and receipt of kidney transplantation. Methods: Key informant interviews were conducted among transplant nephrologists, nephrologists, transplant social workers, and transplant coordinators to determine barriers to transplantation among African Americans compared to whites with end-stage renal disease (ESRD). Analysis: Thirty-eight interviews were audio recorded and transcribed to hardcopy for content analysis. Grounded theory was used to determine dominant themes within the interviews. Reliability and validity were ensured by several coinvestigators independently sorting verbatim responses used for generating themes and subsequent explanations. Results: Several major categories arose from analysis of the transcripts. Under the category of personal and social responsibility for kidney transplantation, interviews revealed 4 major themes: negative personal behaviors, acquisition of and lack of self-treatment of comorbid conditions, lack of individual responsibility, and the need for more social responsibility. Many providers perceived patients as being largely responsible for the development of ESRD, while some providers expressed the idea that more social responsibility was needed to improve poor health status and disparities in kidney transplantation rates. Conclusion: Kidney disease health providers seemed torn between notions of patients' accountability and social responsibility for racial disparities in chronic kidney disease and ESRD. Further research is needed to clarify which aspects contribute most to disparities in access to transplantation. C1 [Spigner, Clarence; Lyles, Courtney Rees; Young, Bessie A.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Sabin, Janice] Univ Washington, Dept Med Educ & Biomed Informat, Seattle, WA 98195 USA. [Young, Bessie A.] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Davis, Connie] Univ Washington, Div Nephrol & Transplantat, Seattle, WA 98195 USA. [Galvin, Georgia; Young, Bessie A.] Puget Sound Hlth Care Syst, Vet Adm, Seattle, WA USA. RP Young, BA (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,152-E, Seattle, WA 98108 USA. EM youngb@u.wash-ington.edu FU NIH [R01DK079745]; National Institute of Diabetes and Digestive and Kidney Diseases; Veterans Affairs Puget Sound Health Care System, Seattle, Washington FX The project described was supported by Dr Young's NIH grant award (R01DK079745) from the National Institute of Diabetes and Digestive and Kidney Diseases. This material is also the result of work supported by resources (Dr Young) from the Veterans Affairs Puget Sound Health Care System, Seattle, Washington. NR 37 TC 2 Z9 2 U1 2 U2 8 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 SEP-OCT PY 2011 VL 103 IS 9-10 BP 879 EP 884 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 869BU UT WOS:000298571500012 PM 22364056 ER PT J AU Buscher, A Hartman, C Kallen, MA Giordano, TP AF Buscher, April Hartman, Christine Kallen, Michael A. Giordano, Thomas P. TI Validity of Self-Report Measures in Assessing Antiretroviral Adherence of Newly Diagnosed, HAART-Naive, HIV Patients SO HIV CLINICAL TRIALS LA English DT Article DE adherence; cohort study; HIV; self-report; Spanish ID THERAPY ADHERENCE; VIRAL SUPPRESSION; CLINICAL-PRACTICE; QUESTIONNAIRE; TRIALS AB Purpose: To compare the performance of self-report instruments assessing adherence to antiretroviral therapy (ART) in patients starting ART for the first time and in a predominately Hispanic population. Methods: Of 184 patients in a prospective observational cohort study of newly diagnosed, minority patients of low socioeconomic status, 54 were given Medication Event Monitoring System (MEMS) caps for their boosted protease inhibitor (RI) or non-nucleoside reverse transcriptase inhibitor (NNRTI). They completed a 4-week recall visual analogue scale (VAS), the Adult AIDS Clinical Trial Group (AACTG) 4-day recall instrument, and a 1-month recall qualitative single-item measure every 3 months for up to 18 months in English or Spanish. Electronic pharmacy records recorded refill dates. Spearman correlation coefficients were calculated to compare self-report measures with MEMS data and pharmacy data. Results: Of 46 patients with MEMS data, mean adherence was 84.7% (SD 35.6) by MEMS, 84.5% (SD 15.1) by pharmacy, 95.4% (SD 11.9) by VAS, 95.8% (SD 17.2) by AACTG, and 87.6% (SD 28.2) by qualitative single item. The correlation coefficient (CC) of VAS with MEMS was 0.37 (P < .01), and with pharmacy it was 0.34 (P < .01). The CC of the AACTG with MEMS was 0.32 (P < .01), and with pharmacy it was 0.28 (P < .01). The qualitative single item had a CC with MEMS of 0.24 (P < .01) and with pharmacy of 0.32 (P < .01). Spanish-speaking patients' VAS adherence had a CC of 0.40 (P < .01) with MEMS. Conclusions: The VAS, AACTG, and qualitative single-item measures correlated significantly with MEMS and pharmacy data. Our data support self-administration of the VAS, even in Spanish speakers. C1 [Buscher, April; Hartman, Christine; Giordano, Thomas P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Buscher, April; Hartman, Christine; Giordano, Thomas P.] Michael E DeBakey VA Med Ctr, Houston Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Kallen, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Gen Internal Med, Houston, TX 77030 USA. RP Giordano, TP (reprint author), Michael E DeBakey VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM tpg@bcm.tmc.edu FU National Institute of Mental Health (NIMH) [R34MH074360]; Agency for Healthcare Research and Quality (AHRQ) [U18HS016093]; Baylor/UT Houston Center for AIDS [P30AI036211]; NIH HIV [T32AI07456] FX Supported by National Institute of Mental Health (NIMH) grant R34MH074360, Agency for Healthcare Research and Quality (AHRQ) grant U18HS016093, the Baylor/UT Houston Center for AIDS Research grant P30AI036211, NIH HIV T32AI07456, and the facilities and resources of the Harris County Hospital District and the Michael E. DeBakey VA Medical Center. Dr. Giordano is a researcher at the Michael E. DeBakey VA Medical Center Health Services Research and Development Center of Excellence, Houston, Texas. The views expressed in this article are those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs. NR 25 TC 22 Z9 23 U1 0 U2 5 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD SEP-OCT PY 2011 VL 12 IS 5 BP 244 EP 254 DI 10.1310/hct1205-244 PG 11 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 847UT UT WOS:000296998700002 PM 22180522 ER PT J AU Tobin, MJ AF Tobin, Martin J. TI The new irrationalism in weaning A nova irracionalidade no desmame SO JORNAL BRASILEIRO DE PNEUMOLOGIA LA English DT Editorial Material ID MECHANICAL VENTILATION; SUPPORT C1 [Tobin, Martin J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. [Tobin, Martin J.] Loyola Univ Chicago, Stritch Sch Med, Hines, IL USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU SOC BRASILEIRA PNEUMOLOGIA TISIOLOGIA PI BRASILIA DF PA SEPS 714-719, BLOCO E ASA SUL, SALAS 220-223, BRASILIA DF, CEP70390-145, BRAZIL SN 1806-3713 J9 J BRAS PNEUMOL JI J. Bras. Pneumol. PD SEP-OCT PY 2011 VL 37 IS 5 BP 571 EP 573 PG 3 WC Respiratory System SC Respiratory System GA 837PA UT WOS:000296214500001 PM 22042386 ER PT J AU Gurrera, RJ Caroff, SN Cohen, A Carroll, BT DeRoos, F Francis, A Frucht, S Gupta, S Levenson, JL Mahmood, A Mann, SC Policastro, MA Rosebush, PI Rosenberg, H Sachdev, PS Trollor, JN Velamoor, VR Watson, CB Wilkinson, JR AF Gurrera, Ronald J. Caroff, Stanley N. Cohen, Abigail Carroll, Brendan T. DeRoos, Francis Francis, Andrew Frucht, Steven Gupta, Sanjay Levenson, James L. Mahmood, Ahsan Mann, Stephan C. Policastro, Michael A. Rosebush, Patricia I. Rosenberg, Henry Sachdev, Perminder S. Trollor, Julian N. Velamoor, Varadaraj R. Watson, Charles B. Wilkinson, Jayne R. TI An International Consensus Study of Neuroleptic Malignant Syndrome Diagnostic Criteria Using the Delphi Method SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SYMPTOMS; SCALE AB Objective: The lack of generally accepted diagnostic criteria for neuroleptic malignant syndrome (NMS) impedes research and clinical management of patients receiving antipsychotic medications The purpose of this study was to develop NMS diagnostic criteria reflecting a broad consensus among clinical knowledge experts, represented by an international multispecialty physician panel. Participants: Eleven psychiatrists, 2 neurologists, 2 anesthesiologists, and 2 emergency medicine specialists participated in a formal Delphi consensus procedure. Evidence: A core bibliography consisting of 12 prominent, current reviews of the NMS literature was identified by an objective, comprehensive electronic search strategy. Each panel member was given a copy of these references and asked to examine them before commencing the survey process. Consensus Process: After reviewing the core bibliography, panel members were asked to list any clinical signs or symptoms or diagnostic studies that they believed, on the basis of their knowledge and clinical experience, were useful in making a diagnosis of NMS. In subsequent survey rounds, panel members assigned priority points to these items, and items that failed to receive a minimum priority score were eliminated from the next round. Information about individual panel member responses was fed back to the group anonymously in the form of the group median or mean and the number of members who had ranked or scored each survey item. The a priori consensus endpoint was defined operationally as a change of 10% or less in the mean priority score for any individual item, and an average absolute value change of 5% or less across all items, between consecutive rounds. The survey was conducted from January 2009 through September 2009. Results: Consensus was reached on the fifth round regarding the following criteria: recent dopamine antagonist exposure, or dopamine agonist withdrawal; hyperthermia; rigidity; mental status alteration; creatine kinase elevation; sympathetic nervous system lability; tachycardia plus tachypnea; and a negative work-up for other causes. The panel also reached a consensus on the relative importance of these criteria and on the following critical values for quantitative criteria: hyperthermia, > 100.4 degrees F or > 38.0 degrees C on at least 2 occasions; creatine kinase elevation, at least 4 times the upper limit of normal; blood pressure elevation, >= 25% above baseline; blood pressure fluctuation, >= 20 mm Hg (diastolic) or >= 25 mm Hg (systolic) change within 24 hours; tachycardia, >= 25% above baseline; and tachypnea, >= 50% above baseline. Conclusions: These diagnostic criteria significantly advance the field because they represent the consensus of an international multispecialty expert panel, include critical values, provide guidance regarding the relative importance of individual elements, and are less influenced by particular theoretical biases than most previously published criteria. They require validation before being applied in clinical settings. J Clin Psychiatry 2011;72(9):1222-1228 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Gurrera, Ronald J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Gurrera, Ronald J.] Vet Affairs VA Boston Healthcare Syst, Boston, MA USA. [Caroff, Stanley N.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Cohen, Abigail] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [DeRoos, Francis] Univ Penn, Sch Med, Dept Emergency Med, Philadelphia, PA 19104 USA. [Wilkinson, Jayne R.] Univ Penn, Sch Med, Dept Clin Neurol, Philadelphia, PA 19104 USA. [Caroff, Stanley N.; DeRoos, Francis; Wilkinson, Jayne R.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Carroll, Brendan T.] Ohio Univ, Coll Osteopath Med, Athens, OH 45701 USA. [Carroll, Brendan T.] Chillicothe VA Med Ctr, Chillicothe, OH USA. [Francis, Andrew] SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. [Frucht, Steven] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Gupta, Sanjay] SUNY Syracuse, Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Gupta, Sanjay; Mahmood, Ahsan] SUNY Buffalo, Dept Psychiat, Buffalo, NY 14260 USA. [Levenson, James L.] Virginia Commonwealth Univ, Sch Med, Dept Psychiat, Richmond, VA 23284 USA. [Mahmood, Ahsan] Buffalo Psychiat Ctr, Buffalo, NY USA. [Mann, Stephan C.] Univ Louisville, Sch Med, Dept Psychiat & Behav Sci, Louisville, KY 40292 USA. [Mann, Stephan C.] Cent Montgomery Mental Hlth & Mental Retardat Ctr, Norristown, PA USA. [Policastro, Michael A.] Wright State Univ, Boonshoft Sch Med, Dept Emergency Med, Dayton, OH 45435 USA. [Policastro, Michael A.] Good Samaritan Hosp, Cincinnati, OH USA. [Rosebush, Patricia I.] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. [Rosenberg, Henry] St Barnabas Hosp, Dept Med Educ, Livingston, NJ USA. [Rosenberg, Henry] St Barnabas Hosp, Dept Clin Res, Livingston, NJ USA. [Rosenberg, Henry] Malignant Hyperthermia Assoc US, Sherburne, NY USA. [Sachdev, Perminder S.; Trollor, Julian N.] Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. [Trollor, Julian N.] Univ New S Wales, Dept Dev Disabil Neuropsychiat, Sydney, NSW, Australia. [Sachdev, Perminder S.] Prince Wales Hosp, Inst Neuropsychiat, Randwick, NSW 2031, Australia. [Velamoor, Varadaraj R.] Univ Western Ontario, Dept Psychiat, Schulich Sch Med & Dent, London, ON N6A 3K7, Canada. [Watson, Charles B.] Yale New Haven Hlth Syst, Bridgeport Hosp, Dept Anesthesia, Bridgeport, CT USA. RP Gurrera, RJ (reprint author), Vet Affairs Boston Healthcare Syst, 940 Belmont St,116A, Brockton, MA 02301 USA. EM ronald.gurrera@va.gov RI Cohen, Abigail/K-9180-2013 OI Cohen, Abigail/0000-0002-7425-7218; Sachdev, Perminder/0000-0002-9595-3220; Trollor, Julian/0000-0002-7685-2977 FU Eli Lilly; GlaxoSmithKline; AstraZeneca; Pfizer; Takeda; Forest; Myriad; Ono; NMSIS; AstraZeneca Pharmaceuticals LP [48804]; National Center for Research Resources [UL1-RR024134]; VA Boston Healthcare System; American Academy of Child & Adolescent Psychiatry; Malignant Hyperthermia Association of the United States FX Dr Gurrera has served as a volunteer consultant for the Neuroleptic Malignant Syndrome Information Service (NMSIS) and is a member of the NMSIS Professional Advisory Council. Dr Caroff has served as a consultant for Eli Lilly and is a member of the NMSIS Professional Advisory Council. Dr Carroll has received speakers bureau honoraria from Eli Lilly and Pfizer and is an NMSIS hotline volunteer consultant. Dr Francis is a member of the NMSIS Professional Advisory Council. Dr Frucht has served as a consultant for UCB Pharma, Lundbeck, GE Healthcare, Gerson Lehrman Group, and Guidepoint Global and is a member of the NMSIS Professional Advisory Council. Dr Gupta has been a consultant for Eli Lilly; has received research support from Eli Lilly, GlaxoSmithKline, AstraZeneca, Pfizer, Takeda, Forest, Myriad, and Ono; has served on advisory panels for Eli Lilly and Pamlab; has received speakers bureau honoraria from Eli Lilly, GlaxoSmithKline, Novartis, Forest, Merck, and AstraZeneca; and is a member of the NMSIS Professional Advisory Council. Dr Levenson is a member of the NMSIS Professional Advisory Council. Dr Mann is an NMSIS hotline volunteer consultant. Dr Policastro has been an employee of Qualified Emergency Specialists, Cincinnati, Ohio; has been a consultant to the US Drug Enforcement Administration and Dyax Corporation; has received honoraria from the Malignant Hyperthermia Association of the United States and NMSIS; and has served as an advisory panel member for Dyax Corporation and the Malignant Hyperthermia Association of the United States. Drs Rosebush and Rosenberg are members of the NMSIS Professional Advisory Council. Drs Sachdev and Trollor are NMSIS International Partners. Dr Velamoor is a member of the NMSIS Professional Advisory Council. Dr Watson is an NMSIS hotline volunteer consultant. Drs Cohen, DeRoos, Mahmood, and Wilkinson report no financial relationships with any commercial interest. All expert panel members received a small honorarium from NMSIS for their participation.; This study received administrative support from NMSIS (www.nmsis.org) and received financial support from the Shah Educational Awareness Fund of NMSIS and from an independent educational grant (#48804) from AstraZeneca Pharmaceuticals LP to NMSIS. Dr. Cohen was supported by the Outcomes Measurement Methods Core of the Center for Translational Science Award, National Center for Research Resources grant number UL1-RR024134. This work was also supported by the resources of and the use of the facilities at the VA Boston Healthcare System.; The authors thank Jeffrey R. Strawn, MD, of the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, for his assistance in assembling the core bibliography for the expert panel and Marilyn Green Larach, MD, FAAP, who is affiliated with the North American Malignant Hyperthermia Registry of the Malignant Hyperthermia Association of the United States, Pittsburgh, Pennsylvania, for her helpful comments about the Delphi consensus process. Dr Strawn has received research support from the American Academy of Child & Adolescent Psychiatry and Eli Lilly and has received honoraria from Qualcom Medical Media. Dr Larach has received a consulting fee from the Malignant Hyperthermia Association of the United States to develop an ambulatory surgery center transfer-of-care document for malignant hyperthermia patients and has been reimbursed by the Association for travel expenses to attend scientific conferences. NR 29 TC 38 Z9 40 U1 0 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2011 VL 72 IS 9 BP 1222 EP 1228 DI 10.4088/JCP.10m06438 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 828LO UT WOS:000295502700009 PM 21733489 ER PT J AU Denisenko, O Lin, BY Bagby, S AF Denisenko, Oleg Lin, Baoyu Bagby, Susan TI Maternal Malnutrition Upregulates Expression and Alters Splicing of Angiotensin II Receptor Gene, AT1R, in Prenatal and Neonatal Kidneys SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Meeting Abstract C1 [Denisenko, Oleg] Univ Washington, Seattle, WA 98195 USA. [Bagby, Susan] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD SEP PY 2011 VL 2 SU 1 BP S25 EP S25 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 837CK UT WOS:000296168500078 ER PT J AU DuPriest, EA Kupfer, P Lin, B Sekiguchi, K Morgan, TK Saunders, KE Chatkupt, TT Purnell, JQ Bagby, SP AF DuPriest, E. A. Kupfer, P. Lin, B. Sekiguchi, K. Morgan, T. K. Saunders, K. E. Chatkupt, T. T. Purnell, J. Q. Bagby, S. P. TI Prevention of Accelerated Growth in Nutritionally Programmed Offspring Does Not Ameliorate Adipose Tissue Dysfunction SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Meeting Abstract C1 [DuPriest, E. A.; Kupfer, P.; Lin, B.; Sekiguchi, K.; Morgan, T. K.; Saunders, K. E.; Chatkupt, T. T.; Purnell, J. Q.; Bagby, S. P.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [DuPriest, E. A.; Kupfer, P.; Lin, B.; Sekiguchi, K.; Bagby, S. P.] Portland VA Med Ctr, Portland, OR USA. [DuPriest, E. A.] Warner Pacific Coll, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD SEP PY 2011 VL 2 SU 1 BP S60 EP S60 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 837CK UT WOS:000296168500198 ER PT J AU DuPriest, EA Kupfer, P Lin, BY Sekiguchi, K Morgan, TK Saunders, KE Chatkupt, TT Purnell, JQ Bagby, SP AF DuPriest, Elizabeth A. Kupfer, Philipp Lin, Baoyu Sekiguchi, Kaiu Morgan, Terry K. Saunders, Kim E. Chatkupt, Tom T. Purnell, Jonathan Q. Bagby, Susan P. TI Altered Adipocyte Structure and Function in Nutritionally Programmed Microswine Offspring SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Meeting Abstract C1 [DuPriest, Elizabeth A.; Kupfer, Philipp; Lin, Baoyu; Sekiguchi, Kaiu; Morgan, Terry K.; Saunders, Kim E.; Chatkupt, Tom T.; Purnell, Jonathan Q.; Bagby, Susan P.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [DuPriest, Elizabeth A.; Kupfer, Philipp; Lin, Baoyu; Sekiguchi, Kaiu; Bagby, Susan P.] Portland VA Med Ctr, Portland, OR USA. [DuPriest, Elizabeth A.] Warner Pacific Coll, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD SEP PY 2011 VL 2 SU 1 BP S54 EP S54 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 837CK UT WOS:000296168500179 ER PT J AU Kirchner, JE Farmer, MS Shue, VM Blevins, D Sullivan, G AF Kirchner, Joann E. Farmer, Mary Sue Shue, Valorie M. Blevins, Dean Sullivan, Greer TI Partnering With Communities to Address the Mental Health Needs of Rural Veterans SO JOURNAL OF RURAL HEALTH LA English DT Article DE clergy; criminal justice; education; mental health; rural veterans ID POSTTRAUMATIC-STRESS-DISORDER; COMORBIDITY SURVEY REPLICATION; UNITED-STATES; URBAN DIFFERENCES; SERVICES UTILIZATION; DEPRESSION; CARE; PREVALENCE; AFGHANISTAN; OUTCOMES AB Purpose: Many veterans who face mental illness and live in rural areas never obtain the mental health care they need. To address these needs, it is important to reach out to community stakeholders who are likely to have frequent interactions with veterans, particularly those returning from Operations Enduring and Iraqi Freedom (OEF/OIF). Methods: Three community stakeholder groups-clergy, postsecondary educators, and criminal justice personnel-are of particular importance for OEF/OIF veterans living in rural areas and may be more likely to come into contact with rural veterans struggling with mental illness or substance abuse than the formal health care system. This article briefly describes the conceptualization, development, initial implementation, and early evaluation of a Veterans Affairs (VA) medical center-based program designed to improve engagement in, and access to, mental health care for veterans returning to rural areas. Findings: One year since initial funding, 90 stakeholders have attended formal training workshops (criminal justice personnel = 36; educators = 31; clergy = 23). Two training formats (a 2-hour workshop and an intensive 2.5-day workshop) have been developed and provided to clergy in 1 rural county with another county scheduled for training. A veteran outreach initiative, which has received 32 referrals for various student services, has been established on 4 rural college campuses. A Veterans Treatment Court also has been established with 16 referrals for eligibility assessments. Conclusions: While this pilot program is in the early stages of evaluation, its success to date has encouraged program and VA clinical leadership to expand beyond the original sites. C1 [Kirchner, Joann E.] US Dept Vet Affairs, Mental Hlth Qual Enhancement Res Initiat, N Little Rock, AR USA. [Farmer, Mary Sue; Blevins, Dean; Sullivan, Greer] US Dept Vet Affairs, Mental Illness Res Educ Clin Ctr, N Little Rock, AR USA. [Kirchner, Joann E.; Shue, Valorie M.; Blevins, Dean; Sullivan, Greer] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Kirchner, Joann E.; Blevins, Dean; Sullivan, Greer] US Dept Vet Affairs, Hlth Serv Res & Dev Ctr Mental Healthcare & Outco, N Little Rock, AR USA. RP Kirchner, JE (reprint author), VA HSR & Ctr Mental Healthcare & Outcomes Res, 2200 Ft Roots Dr,Bldg 58, N Little Rock, AR 72114 USA. EM kirchnerjoanne@uams.edu FU United States Department of Veterans Affairs Office of Rural Health; South Central Mental Illness Research Education Clinical Center FX We would like to thank the clinicians, OEF-OIF Veterans, and clinical teams who made this work possible. Specifically, we would like to acknowledge Michael T. Lambert, LCSW; Bridgett Larkin, MBA (OEF-IOF Veteran); William M. Moore, PhD; Jamie Mucciarelli, MA (OEF/OIF Veteran); Vince Roca, PhD; Steve Sullivan, M.Div, Th.M; Elizabeth White, LMSW; and Linda Worley, MD. This project was supported by the United States Department of Veterans Affairs Office of Rural Health and South Central Mental Illness Research Education Clinical Center. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. For further information contact: JoAnn E. Kirchner, MD, VA HSR & D Center for Mental Healthcare and Outcomes Research, 2200 Fort Roots Drive, Bldg 58, North Little Rock, AR 72114; e-mail kirchnerjoanne@uams.edu. NR 70 TC 7 Z9 7 U1 3 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0890-765X J9 J RURAL HEALTH JI J. Rural Health PD FAL PY 2011 VL 27 IS 4 BP 416 EP 424 DI 10.1111/j.1748-0361.2011.00362.x PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 833HU UT WOS:000295875200011 PM 21967386 ER PT J AU Bauman, WA Emmons, RR Cirnigliaro, CM Kirshblum, SC Spungen, AM AF A. Bauman, William Emmons, Racine R. Cirnigliaro, Christopher M. Kirshblum, Steven C. Spungen, Ann M. TI An effective oral vitamin D replacement therapy in persons with spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Vitamin D deficiency; Nutritional supplementation; Calcium; Vitamin D; Osteoporosis; Spinal cord injuries; Bone loss; Cholecalciferol; Paraplegia; Tetraplegia; Veterans ID BONE-MINERAL DENSITY; D DEFICIENCY; COLORECTAL-CANCER; RISK; DISEASE; MORTALITY; CALCIUM; HEALTH; ADULTS; INDIVIDUALS AB Background/objective: Vitamin D deficiency is prevalent in chronic spinal cord injury (SCI). A 3-month course of oral vitamin D-3 to 'normalize' serum vitamin D levels was investigated. Design: Prospective drug-intervention study. Setting: VA Medical Center; private rehabilitation facility. Methods: Seven individuals with chronic SCI and vitamin D deficiency completed 3 months of oral vitamin D-3 (i.e. cholecalciferol) supplementation. At screening, baseline, and months 1 and 3, blood was collected for serum calcium, 25 hydroxyvitamin D [25(OH) D], intact parathyroid hormone (iPTH), and N-telopeptide (NTx); 24-hour urine for calcium, creatinine, and NTx was performed. Oral vitamin D-3 (2000 IU daily) and elemental calcium (1.3 g daily) were prescribed for 90 days. The results are expressed as mean +/- standard deviation (SD). Analysis of variance with a Fisher's post-hoc analysis was performed to test for differences between study visits. Subjects were classified as deficient (<20 ng/ml), relatively deficient (20-30 ng/ml), or not deficient (>30 ng/ml) in 25(OH) D. Results: Serum 25(OH) D levels were greater at months 1 and 3 than at baseline (26 +/- 6 and 48 +/- 17 vs. 14 +/- 2 ng/ml; P = 0.005). Six of seven subjects were no longer deficient [25(OH) D >30 ng/ml] by month 3. Serum iPTH levels were significantly decreased at month 1 and month 3; serum NTx levels were significantly lower at month 3 than at baseline. Serum and urinary calcium levels remained within the normal range. Conclusion: A daily prescription of 2000 IU of oral vitamin D-3 for 3 months safely raised serum 25(OH) D levels into the normal range in persons with chronic SCI on calcium supplementation. C1 [A. Bauman, William; Emmons, Racine R.; Cirnigliaro, Christopher M.; Spungen, Ann M.] James J Peters VA Med Ctr, Dept Vet Affairs, Rehabil Res & Dev Ctr Excellence Med Consequences, Bronx, NY 10468 USA. [A. Bauman, William; Spungen, Ann M.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [A. Bauman, William; Spungen, Ann M.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Emmons, Racine R.] Columbia Univ Teachers Coll, New York, NY 10027 USA. [Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA. [Kirshblum, Steven C.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Phys Med & Rehabil, Newark, NJ 07103 USA. RP Bauman, WA (reprint author), James J Peters VA Med Ctr, Dept Vet Affairs, Rehabil Res & Dev Ctr Excellence Med Consequences, Room 7A-13,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM william.bauman@va.gov NR 43 TC 5 Z9 6 U1 1 U2 12 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD SEP PY 2011 VL 34 IS 5 BP 455 EP 460 DI 10.1179/2045772311Y.0000000032 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 835OS UT WOS:000296046300003 PM 22118252 ER PT J AU Stroud, MW Bombardier, CH Dyer, JR Rimmele, CT Esselman, PC AF Stroud, Michael W. Bombardier, Charles H. Dyer, Joshua R. Rimmele, Carl T. Esselman, Peter C. TI Preinjury alcohol and drug use among persons with spinal cord injury: Implications for rehabilitation SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Alcohol; Drug; Substance-related disorders; Spinal cord injuries; Rehabilitation; Paraplegia; Tetraplegia; Toxicology screening ID TRAUMATIC BRAIN-INJURY; SUBSTANCE-ABUSE; CHANGE QUESTIONNAIRE; USE DISORDERS; READINESS; RISK; INTERVENTIONS; COMPLICATIONS; MAGNITUDE; DRINKERS AB Context/objective: To describe preinjury alcohol and drug use and opportunities for secondary prevention among persons with recent spinal cord injury (SCI). Design: Survey. Setting: Acute inpatient rehabilitation program. Participants: Participants were 118 (84.8%) of 139 consecutive admissions who met inclusion criteria and were screened for preinjury alcohol and drug use. Interventions: None. Outcome measures: Alcohol and drug use, toxicology results, alcohol problems, readiness to change, and treatment preferences. Results: Participants were on average 37 years old, 84% were men, and 85% were white. Fifty-one percent of the sample was considered 'at-risk' drinkers. Significant lifetime alcohol-related problems were reported by 38% of the total sample. Thirty-three percent reported recent illicit drug use and 44% of the 82 cases with toxicology results were positive for illicit drugs. Seventy-one percent of at-risk drinkers reported either considering changes in alcohol use or already taking action. Forty-one percent reported interest in trying substance abuse treatment or Alcoholics Anonymous (AA). Motivation to change alcohol use was significantly and positively associated with self-reported indicators of alcohol problem severity. Conclusion: Preinjury alcohol and drug abuse are common among persons with recent SCI. Substance abuse screening is feasible and detects not only salient clinical problems but also significant motivation to change and interest in AA or treatment, all of which represent an important window of opportunity for appropriate brief interventions and referrals. In contrast with the idea that alcoholism is a 'disease of denial', the majority of at-risk drinkers with new onset SCI indicate they are considering making changes. C1 [Bombardier, Charles H.] Univ Washington, Harborview Med Ctr, Dept Rehabil Med, Sch Med, Seattle, WA 98104 USA. [Stroud, Michael W.] Vet Adm Med Ctr, Denver, CO USA. [Rimmele, Carl T.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Rimmele, Carl T.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Bombardier, CH (reprint author), Univ Washington, Harborview Med Ctr, Dept Rehabil Med, Sch Med, Box 359612,325 9th Ave, Seattle, WA 98104 USA. EM chb@uw.edu FU Northwest Regional Spinal Cord Injury System; National Institute on Disability and Rehabilitation Research [H133N50025, H133N060033] FX This research was supported by the Northwest Regional Spinal Cord Injury System grant and funded by the National Institute on Disability and Rehabilitation Research (H133N50025; H133N060033). The contents of this paper are solely the responsibility of the authors and do not represent the official views of the granting agency. No commercial party having a direct financial interest in the results of the research has or will confer a benefit upon the authors or upon any organization with which the authors are associated. NR 45 TC 3 Z9 4 U1 2 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 SEP PY 2011 VL 34 IS 5 BP 461 EP 472 DI 10.1179/2045772311Y.0000000033 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 835OS UT WOS:000296046300004 PM 22118253 ER PT J AU Turner, PV Brabb, T Pekow, C Vasbinder, MA AF Turner, Patricia V. Brabb, Thea Pekow, Cynthia Vasbinder, Mary Ann TI Administration of Substances to Laboratory Animals: Routes of Administration and Factors to Consider SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Editorial Material ID HYDRODYNAMIC GENE DELIVERY; INBRED MOUSE STRAINS; DRUG-DELIVERY; INTRAPERITONEAL INJECTIONS; INTRAMUSCULAR INJECTION; SELF-MUTILATION; GASTROINTESTINAL ABSORPTION; INTRAARTERIAL INJECTION; PARENTERAL-NUTRITION; EPIDURAL ANALGESIA AB Administration of substances to laboratory animals requires careful consideration and planning to optimize delivery of the agent to the animal while minimizing potential adverse experiences from the procedure. For all species, many different routes are available for administration of substances. The research team and IACUC members should be aware of reasons for selecting specific routes and of training and competency necessary for personnel to use these routes effectively. Once a route is selected, issues such as volume of administration, site of delivery, pH of the substance, and other factors must be considered to refine the technique. Inadequate training or inattention to detail during this aspect of a study may result in unintentional adverse effects on experimental animals and confounded results. C1 [Turner, Patricia V.] Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. [Brabb, Thea] Univ Washington, Sch Med, Dept Comparat Med, Seattle, WA 98195 USA. [Pekow, Cynthia] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Vasbinder, Mary Ann] GlaxoSmithKline, Platform Technol & Sci Qual & Risk Management, Res Triangle Pk, NC USA. RP Turner, PV (reprint author), Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. EM pvturner@uoguelph.ca NR 145 TC 86 Z9 90 U1 10 U2 43 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 SEP PY 2011 VL 50 IS 5 BP 600 EP 613 PG 14 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 835XJ UT WOS:000296070000001 PM 22330705 ER PT J AU Turner, PV Pekow, C Vasbinder, MA Brabb, T AF Turner, Patricia V. Pekow, Cynthia Vasbinder, Mary Ann Brabb, Thea TI Administration of Substances to Laboratory Animals: Equipment Considerations, Vehicle Selection, and Solute Preparation SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Editorial Material ID VASCULAR ACCESS PORTS; BIOMEDICAL-RESEARCH; RHESUS-MONKEYS; RESTRAINT; CATHETER; PATENCY; RAT; DIMETHYLSULFOXIDE; CYCLODEXTRIN; FORMULATIONS AB Administration of substances to laboratory animals requires careful consideration and planning to optimize delivery of the agent to the animal while minimizing potential adverse experiences from the procedure. The equipment selected to deliver substances to animals depends on the length of the study and the nature of the material being administered. This selection provides a significant opportunity for refining animal treatment. Similarly, when substances are administered as solutions or suspensions, attention should be given to selection of vehicles and methods used for preparing the solutions and suspensions. The research team, veterinarian, technical personnel, and IACUC members should be aware of reasons underlying selection of equipment for substance delivery and should consider carefully how substances will be prepared and stored prior to administration to animals. Failure to consider these factors during experimental planning may result in unintentional adverse effects on experimental animals and confounded results. C1 [Turner, Patricia V.] Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. [Pekow, Cynthia] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Brabb, Thea] Univ Washington, Sch Med, Dept Comparat Med, Seattle, WA 98195 USA. [Vasbinder, Mary Ann] GlaxoSmithKline, Platform Technol & Sci Qual & Risk Management, Res Triangle Pk, NC USA. RP Turner, PV (reprint author), Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. EM pvturner@uoguelph.ca NR 89 TC 33 Z9 34 U1 3 U2 14 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 SEP PY 2011 VL 50 IS 5 BP 614 EP 627 PG 14 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 835XJ UT WOS:000296070000002 PM 22330706 ER PT J AU Swanson, LK Beckman, WJ Dehlinger, K AF Swanson, L. K. Beckman, W. J. Dehlinger, K. TI Characterization of Prairie Vole (Microtus ochrogaster) Pup Development SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Swanson, L. K.; Beckman, W. J.; Dehlinger, K.] Portland VA Med Ctr, Vet Med Unit, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 SEP PY 2011 VL 50 IS 5 BP 776 EP 776 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 835XJ UT WOS:000296070000259 ER PT J AU Sales, AE Lapham, GG Squires, J Hutchinson, A Almenoff, P Sharp, ND Lowy, E Li, YF AF Sales, Anne E. Lapham, Gwendolyn G. Squires, Janet Hutchinson, Alison Almenoff, Peter Sharp, Nancy D. Lowy, Elliott Li, Yu-Fang TI Organizational Factors Associated With Decreased Mortality Among Veterans Affairs Patients With an ICU Stay SO CIN-COMPUTERS INFORMATICS NURSING LA English DT Article DE Electronic record; Hospital organization; In-hospital mortality; Intensive care ID INTENSIVE-CARE UNITS; ILL HOSPITALIZED ADULTS; OUTCOMES; QUALITY; IMPACT AB In-hospital mortality rates associated with an ICU stay are high and vary widely among units. This variation may be related to organizational factors such as staffing patterns, ICU structure, and care processes. We aimed to identify organizational factors associated with variation in in-hospital mortality for patients with an ICU stay. This was a retrospective observational cross-sectional study using administrative data from 34 093 patients from 171 ICUs in 119 Veterans Health Administration hospitals. Staffing and patient data came from Veterans Health Administration national databases. ICU characteristics came from a survey in 2004 of ICUs within the Veterans Health Administration. We conducted multilevel multivariable estimation with patient-, unit-, and hospital-level data. The primary outcome was in-hospital mortality. Of 34 093 patients, 2141 (6.3%) died in the hospital. At the patient level, risk of complications and having a medical diagnosis were significantly associated with a higher risk of mortality. At the unit level, having an interface with the electronic medical record was significantly associated with a lower risk of mortality. The finding that electronic medical records integrated with ICU information systems are associated with lower in-hospital mortality adds support to existing evidence on organizational characteristics associated with in-hospital mortality among ICU patients. C1 [Sales, Anne E.; Squires, Janet; Hutchinson, Alison] Univ Alberta, Fac Nursing, Edmonton, AB T6G 2T4, Canada. [Lapham, Gwendolyn G.; Sharp, Nancy D.; Lowy, Elliott; Li, Yu-Fang] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Almenoff, Peter] VA Cent Off, Washington, DC USA. RP Sales, AE (reprint author), Univ Alberta, Fac Nursing, Edmonton, AB T6G 2T4, Canada. EM anne.sales@ualberta.ca RI Sales, Anne/D-9678-2012 OI Sales, Anne/0000-0001-9360-3334 FU Office of Research and Development, Health Services R&D Service, Department of Veterans Affairs [IIR 01-160] FX This study was supported by the Office of Research and Development, Health Services R&D Service, Department of Veterans Affairs (project number IIR 01-160). NR 18 TC 5 Z9 5 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1538-2931 J9 CIN-COMPUT INFORM NU JI CIN-Comput. Inform. Nurs. PD SEP PY 2011 VL 29 IS 9 BP 496 EP 501 DI 10.1097/NCN.0b013e3182148c47 PG 6 WC Computer Science, Interdisciplinary Applications; Medical Informatics; Nursing SC Computer Science; Medical Informatics; Nursing GA 833IR UT WOS:000295878200004 PM 21983432 ER PT J AU Zhang, Y Nateras, OS Peng, Q Kuranov, RV Harrison, JM Milner, TE Duong, TQ AF Zhang, Yi Nateras, Oscar San Emeterio Peng, Qi Kuranov, Roman V. Harrison, Joseph M. Milner, Thomas E. Duong, Timothy Q. TI Lamina-Specific Anatomic Magnetic Resonance Imaging of the Human Retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; MANGANESE-ENHANCED MRI; BLOOD-FLOW; IN-VIVO; FUNCTIONAL MRI; RAT RETINA; 7 TESLA; QUANTIFICATION; RESOLUTION; THICKNESS AB PURPOSE. Magnetic resonance imaging (MRI) of the human retina faces two major challenges: eye movement and hardware limitation that could preclude human retinal MRI with adequate spatiotemporal resolution. This study investigated eye-fixation stability and high-resolution anatomic MRI of the human retina on a 3-Tesla (T) MRI scanner. Comparison was made with optical coherence tomography (OCT) on the same subjects. METHODS. Eye-fixation stability of protocols used in MRI was evaluated on four normal volunteers using an eye tracker. High-resolution MRI (100 x 200 x 2000 mu m) protocol was developed on a 3-T scanner. Subjects were instructed to maintain stable eye fixation on a target with cued blinks every 8 seconds during MRI. OCT imaging of the retina was performed. Retinal layer thicknesses measured with MRI and OCT were analyzed for matching regions of the same eyes close to the optic nerve head. RESULTS. The temporal SDs of the horizontal and vertical displacements were 78 +/- 51 and 130 +/- 51 mu m (+/- SD, n = 4), respectively. MRI detected three layers within the human retina, consistent with MRI findings in rodent, feline, and baboon retinas. The hyperintense layer 1 closest to the vitreous likely consisted of nerve fiber, ganglion cell, and inner nuclear layer; the hypointense layer 2, the outer nuclear layer and the inner and outer segments; and the hyperintense layer 3, the choroid. The MRI retina/choroid thickness was 711 +/- 37 mu m, 19% (P < 0.05) thicker than OCT thickness (579 +/- 34 mu m). CONCLUSIONS. This study reports high-resolution MRI of laminaspecific structures in the human retina. These initial results are encouraging. Further improvement in spatiotemporal resolution is warranted. (Invest Ophthalmol Vis Sci. 2011;52:7232-7237) DOI:10.1167/iovs.11-7623 C1 [Zhang, Yi; Nateras, Oscar San Emeterio; Peng, Qi; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Zhang, Yi; Nateras, Oscar San Emeterio; Peng, Qi; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Kuranov, Roman V.; Harrison, Joseph M.; 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. [Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008 FU Clinical Translational Science Award; Translational Technology Resource Grant [UL1RR025767]; National Institutes of Health/National Eye Institute [R01 EY014211, EY018855]; Department of Veterans Affairs FX Supported in part by a Clinical Translational Science Award Pilot grant (TQD) and a Translational Technology Resource Grant UL1RR025767 (QP), National Institutes of Health/National Eye Institute Grants R01 EY014211 and EY018855, and Department of Veterans Affairs Merit awards (TQD). NR 46 TC 21 Z9 21 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 SEP PY 2011 VL 52 IS 10 BP 7232 EP 7237 DI 10.1167/iovs.11-7623 PG 6 WC Ophthalmology SC Ophthalmology GA 827YU UT WOS:000295467200027 PM 21828153 ER PT J AU Pham, AN Datta, SK Weber, TJ Walter, LC Colon-Emeric, CS AF Pham, Annalise N. Datta, Santanu K. Weber, Thomas J. Walter, Louise C. Colon-Emeric, Cathleen S. TI Cost-Effectiveness of Oral Bisphosphonates for Osteoporosis at Different Ages and Levels of Life Expectancy SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE osteoporosis; bisphosphonates; cost-effectiveness ID FRACTURE INTERVENTION TRIAL; VERTEBRAL FRACTURES; HIP FRACTURE; UNITED-STATES; BONE-DENSITY; OLDER WOMEN; ALENDRONATE; RISK; RISEDRONATE; MORTALITY AB OBJECTIVES: To evaluate the cost-effectiveness of oral bisphosphonate therapy for osteoporosis in women at different ages and life expectancies. DESIGN: A Markov model was used to analyze oral bisphosphonate treatment for 5 years compared to no intervention. Women at each age were divided into life expectancy quartiles: the lowest 1% to 25% (sickest group), the two middle 26% to 75% (average health group), and the highest 76% to 100% of life expectancy (healthiest group). Simulations were performed for hypothetical cohorts at 5-year intervals with starting ages between 50 and 90 and for each life expectancy group and followed for up to 100 years or until death. Data sources included published fracture rates, costs, utility values, and mortality risks. SETTING: Computer simulation using a societal perspective. PARTICIPANTS: Hypothetical cohort of women with various life expectancies beginning osteoporosis treatment between the age of 50 and 90 years. MEASUREMENTS: Cost per quality-adjusted life years (QALY) gained for 5 years of bisphosphonate therapy compared to no treatment. Cost-effectiveness was defined at a willingness-to-pay of $50,000. RESULTS: In the healthiest group, all costs were less than $18,000 per QALY. In the median quartiles of life expectancy, lifetime costs per QALY were less than $27,000 for patients at all ages; treatment became cost-saving at a starting age of 75 and remained so through a starting age of 85. Even in the sickest group, although osteoporosis treatment was not cost-saving, it remained cost-effective through a starting age of 90 with lifetime costs of less than $43,000 per QALY. CONCLUSION: Treatment with an oral bisphosphonate for 5 years was cost-effective for all women, regardless of quartile of life expectancy. Advanced age should not prevent consideration of osteoporosis treatment based on cost effectiveness, and strategies to improve care, such as nurseled screening programs or electronic medical record tools, are needed. J Am Geriatr Soc 59: 1642-1649, 2011. C1 [Colon-Emeric, Cathleen S.] Duke Univ, Div Geriatr, Med Ctr, Durham, NC 27705 USA. [Weber, Thomas J.] Duke Univ, Div Endocrinol, Med Ctr, Durham, NC 27705 USA. [Datta, Santanu K.] Duke Univ, Div Gen Internal Med, Med Ctr, Durham, NC 27705 USA. [Pham, Annalise N.] Canberra Hosp, Dept Endocrinol, Canberra, ACT, Australia. [Colon-Emeric, Cathleen S.] Durham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. [Datta, Santanu K.] Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res, Durham, NC USA. [Walter, Louise C.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA 94143 USA. RP Colon-Emeric, CS (reprint author), Duke Univ, Div Geriatr, Med Ctr, 508 Fulton St,GRECC 182, Durham, NC 27705 USA. EM colon001@mc.duke.edu FU Presidential Poster Award in Geriatric Syndromes; Novartis; Amgen; Eli Lilly; Wyeth; Pfizer FX Presented as a poster at the Annual Scientific Meeting of the American Geriatrics Society, May 2010, and recipient of the Presidential Poster Award in Geriatric Syndromes.; Dr. Pham received an educational grant from Novartis in 2009 for medical research at Duke University. Dr. Weber receives funding from Amgen, Eli Lilly, and Novartis and is a consultant for Proctor and Gamble and GlaxoSmithKline. Dr. Colon-Emeric receives research funding from Novartis, Wyeth, and Pfizer for osteoporosis-related studies and is a consultant for Novartis and Amgen. NR 43 TC 9 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2011 VL 59 IS 9 BP 1642 EP 1649 DI 10.1111/j.1532-5415.2011.03571.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 829WD UT WOS:000295615000010 PM 21883116 ER PT J AU Morley, JF Weintraub, D Mamikonyan, E Moberg, PJ Siderowf, AD Duda, JE AF Morley, James F. Weintraub, Daniel Mamikonyan, Eugenia Moberg, Paul J. Siderowf, Andrew D. Duda, John E. TI Olfactory Dysfunction Is Associated with Neuropsychiatric Manifestations in Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; olfaction; nonmotor symptoms; psychiatric symptoms; cognitive symptoms ID MINI-MENTAL-STATE; MILD COGNITIVE IMPAIRMENT; NONMOTOR SYMPTOMS; ODOR IDENTIFICATION; DE-NOVO; DEFICITS; RISK; COMMON; APATHY; TESTS AB Hyposmia, psychiatric disorders, and cognitive problems are common nonmotor manifestations in Parkinson's disease, but how they are related remains unclear. We investigated the relationship between olfactory dysfunction and neuropsychiatric manifestations and performed a cross-sectional study of 248 patients at two movement disorders clinics at academic medical centers. Psychiatric measures were the Geriatric Depression Scale-15, Inventory of Depressive Symptomatology, State Anxiety Inventory, Apathy Scale, and Parkinson's Psychosis Rating Scale. Cognitive measures were the Mini-Mental State Examination, Hopkins Verbal Learning Test-Revised, Digit Span, Tower of London-Drexel, and the Stroop Color Word Test. Olfaction was tested with the University of Pennsylvania Smell Identification Test. There was no significant association between olfaction and mood measures, but psychotic symptoms were more common in patients with olfaction scores below the median (30% vs. 12%; P < 0.001). Worse olfaction was associated with poorer memory (Hopkins Verbal Learning Test-Revised delayed recall items: mean [standard deviation], 6.2 [3.2] vs. 8.4 [2.8]; P < 0.001) and executive performance (Tower of London total moves, 52 [38] vs. 34 [21]; P < 0.001). Odor-identification score was a significant predictor of abnormal performance on these cognitive tests after adjustment for age, sex, and disease characteristics in logistic regression models. The relationship between hyposmia, psychosis, and specific cognitive impairments may reflect the anatomic distribution of Lewy pathology and suggests that olfactory dysfunction could be a biomarker of additional extranigral disease. Future prospective studies are warranted to assess whether hyposmia, a very early feature of Parkinson's disease, might be used to predict the appearance of other common nonmotor symptoms. (C) 2011 Movement Disorder Society C1 [Morley, James F.; Weintraub, Daniel; Moberg, Paul J.; Siderowf, Andrew D.; Duda, John E.] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Morley, James F.; Weintraub, Daniel; Moberg, Paul J.; Siderowf, Andrew D.; Duda, John E.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Weintraub, Daniel; Mamikonyan, Eugenia; Moberg, Paul J.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. RP Duda, JE (reprint author), Philadelphia Vet Adm Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM John.Duda@va.gov FU NIH [K23 MH067894, NINDS U10 NS044451-023, NINDS P50 NS053488-01, NINDS R43NS0636071, NINDS R01NS065087]; Teva Pharmaceutical Industries Ltd.; Avid Radiopharmaceuticals, Inc.; Boehringer Ingelheim; National Institutes of Health [NIMH K23 MH067894]; NINDS [P50 NS053488-01, R01NS065087]; NIA [RO1AG031348]; Michael J. Fox Foundation for Parkinson's Research; Institute for Neurodegenerative Disorders; U.S. Department of Veterans Affairs; Michael J. Fox Foundation; Samueli Institute; C.R. Bard, Inc.; Celgene; Clarient, Inc.; Johnson Johnson FX This work was supported by NIH grant K23 MH067894 (to D.W.).; Dr. Morley has received travel funding from Teva Pharmaceutical Industries Ltd. Dr. Weintraub has served on a scientific advisory board for Boehringer Ingelheim; serves on the editorial board of Movement Disorders; has received speaker honoraria from Boehringer Ingelheim, ACADIA Pharmaceuticals, Novartis, Osmotica Pharmaceutical Corp., BrainCells Inc., Merck Serono, Sanofi-aventis, and Pfizer Inc; and has received/receives research support from Avid Radiopharmaceuticals, Inc., Boehringer Ingelheim, National Institutes of Health (NIMH K23 MH067894 [PI], NINDS P50 NS053488-01 [coinvestigator], NIA RO1AG031348 [site PI], and NINDS R01NS065087 [coinvestigator]), and from the Michael J. Fox Foundation for Parkinson's Research. Ms. Mamikonyan reports no disclosures. Dr. Siderowf serves on a scientific advisory board for, and has received speaker honoraria from, Teva Pharmaceutical Industries Ltd.; serves as a consultant for Supernus Pharmaceuticals, Inc.; and receives research support from Avid Radiopharmaceuticals, Inc., the NIH (NINDS U10 NS044451-023 [Site PI], NINDS P50 NS053488-01 [cocore leader and project leader], NINDS R43NS0636071 [site PI], and NINDS R01NS065087 coinvestigator]), and from the Institute for Neurodegenerative Disorders. Dr. Duda serves on a grant review panel for the Michael J. Fox Foundation for Parkinson's Research; receives research support from the U.S. Department of Veterans Affairs (Merit Award [PI]), the Michael J. Fox Foundation, and the Samueli Institute; and holds stock in C.R. Bard, Inc., Celgene, Clarient, Inc., and Johnson & Johnson. NR 53 TC 30 Z9 33 U1 1 U2 5 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 SEP PY 2011 VL 26 IS 11 BP 2051 EP 2057 DI 10.1002/mds.23792 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 827VF UT WOS:000295456300016 PM 21611985 ER PT J AU Leung, FW AF Leung, F. W. TI Treatment of fecal incontinence (FI) by injection of bulking agent into peri-anal tissue - review of observational studies (OS) and randomized controlled trials (RCT) SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract C1 [Leung, F. W.] VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Med Serv, North Hills, CA USA. [Leung, F. W.] VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Res Serv, North Hills, CA USA. [Leung, F. W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 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 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD SEP PY 2011 VL 23 SU 1 SI SI MA 68 BP 21 EP 21 PG 1 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 822NL UT WOS:000295055100069 ER PT J AU Mata, IF Wilhoite, GJ Yearout, D Bacon, JA Cornejo-Olivas, M Mazzetti, P Marca, V Ortega, O Acosta, O Cosentino, C Torres, L Medina, AC Perez-Pastene, C Diaz-Grez, F Vilarino-Guell, C Venegas, P Miranda, M Trujillo-Godoy, O Layson, L Avello, R Dieguez, E Raggio, V Micheli, F Perandones, C Alvarez, V Segura-Aguilar, J Farrer, MJ Zabetian, CP Ross, OA AF Mata, Ignacio F. Wilhoite, Greggory J. Yearout, Dora Bacon, Justin A. Cornejo-Olivas, Mario Mazzetti, Pilar Marca, Victoria Ortega, Olimpio Acosta, Oscar Cosentino, Carlos Torres, Luis Medina, Angel C. Perez-Pastene, Carolina Diaz-Grez, Fernando Vilarino-Gueell, Carles Venegas, Pablo Miranda, Marcelo Trujillo-Godoy, Osvaldo Layson, Luis Avello, Rodrigo Dieguez, Elena Raggio, Victor Micheli, Federico Perandones, Claudia Alvarez, Victoria Segura-Aguilar, Juan Farrer, Matthew J. Zabetian, Cyrus P. Ross, Owen A. TI Lrrk2 p.Q1111H substitution and Parkinson's disease in Latin America SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson disease; Lrrk2; Latin America ID COMPREHENSIVE ANALYSIS; MUTATIONS; FAMILIES; RISK; GENE AB Mutations in the LRRK2 gene are the most common genetic cause of Parkinson's disease, with frequencies displaying a high degree of population-specificity. Although more than 100 coding substitutions have been identified, only seven have been proven to be highly penetrant pathogenic mutations. Studies however are lacking in non-white populations. Recently, Lrrk2 p.Q1111H (rs78365431) was identified in two affected Hispanic brothers and absent in 386 non-Hispanic white healthy controls. We therefore screened this variant in 1460 individuals (1150 PD patients and 310 healthy controls) from 4 Latin American countries (Peru, Chile, Uruguay and Argentina). In our case-control series from Peru and Chile we observed an increased frequency of Lrrk2 p.Q1111H in patients (7.9%) compared to controls (5.4%) although the difference did not reach significance (OR 1.38; p = 0.10). In addition, the frequency of Lrrk2 p.Q1111H varied greatly between populations and further screening in a set of pure Amerindian and pure Spanish controls suggested that this variant likely originated in an Amerindian population. Further studies in other Latin American populations are warranted to assess its role as a risk factor for Parkinson's disease. Screening in Parkinson's disease patients from under-represented populations will increase our understanding of the role of LRRK2 variants in disease risk worldwide. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Mata, Ignacio F.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S182, Seattle, WA 98108 USA. [Mata, Ignacio F.; Yearout, Dora; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Wilhoite, Greggory J.; Bacon, Justin A.; Vilarino-Gueell, Carles; Farrer, Matthew J.; Ross, Owen A.] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA. [Cornejo-Olivas, Mario; Mazzetti, Pilar; Marca, Victoria; Ortega, Olimpio; Segura-Aguilar, Juan] Inst Nacl Ciencias Neurol, Neurogenet Unit, Lima, Peru. [Acosta, Oscar] Univ Nacl Mayor San Marcos, Sch Med, Lima 14, Peru. [Medina, Angel C.] Univ Nacl Altiplano, Puno, Peru. [Perez-Pastene, Carolina; Diaz-Grez, Fernando] Univ Chile, Fac Med, ICBM, Santiago 7, Chile. [Vilarino-Gueell, Carles; Farrer, Matthew J.] Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 1M9, Canada. [Miranda, Marcelo] Clin Las Condes, Santiago, Chile. [Layson, Luis] Hosp Barros Luco, Santiago, Chile. [Dieguez, Elena] Univ Republica, Fac Med, Dept Neurol, Montevideo, Uruguay. [Raggio, Victor] Univ Republica, Fac Med, Dept Genet, Montevideo, Uruguay. [Micheli, Federico; Perandones, Claudia] Hosp Clin Buenos Aires, Dept Neurol, Buenos Aires, DF, Argentina. [Alvarez, Victoria] Hosp Univ Cent Asturias, Inst Invest Nefrol IRSINFRIAT, Lab Genet Mol, Oviedo, Spain. RP Mata, IF (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM nachofm@u.washington.edu RI Micheli, Federico/A-8358-2012; Ross, Owen/D-7573-2013; Vilarino-Guell, Carles/D-8628-2011; Segura-Aguilar, Juan/H-8839-2013 OI Vilarino-Guell, Carles/0000-0002-5612-5940; Segura-Aguilar, Juan/0000-0002-1018-673X; Fernandez Mata, Ignacio/0000-0003-1198-0633; Zabetian, Cyrus/0000-0002-7739-4306; Cornejo-Olivas, Mario /0000-0001-6313-5680 FU National Institutes of Health [R01 NS065070, P50 NS062684, P50 NS072187]; Department of Veterans Affairs [1101BX000531]; FONDECYT [1061083]; Parkinson's Disease Foundation; Michael J. Fox Foundation; family of Carl and Susan Bolch; NIH [R24 TW007988] FX This work was supported by the National Institutes of Health (R01 NS065070, P50 NS062684, P50 NS072187), Department of Veterans Affairs (1101BX000531), FONDECYT (#1061083), Parkinson's Disease Foundation, Michael J. Fox Foundation, and the family of Carl and Susan Bolch. Dr Cornejo-Olivas is the recipient of an NIH Fogarty International Clinical Research Fellowship at Vanderbilt University (R24 TW007988). NR 12 TC 3 Z9 4 U1 1 U2 7 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 SEP PY 2011 VL 17 IS 8 BP 629 EP 631 DI 10.1016/j.parkreldis.2011.05.003 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 831WE UT WOS:000295761000010 PM 21632271 ER PT J AU Stengel, A Goebel-Stengel, M Jawien, J Kobelt, P Tache, Y Lambrecht, NWG AF Stengel, Andreas Goebel-Stengel, Miriam Jawien, Janusz Kobelt, Peter Tache, Yvette Lambrecht, Nils W. G. TI Lipopolysaccharide increases gastric and circulating NUCB2/nesfatin-1 concentrations in rats SO PEPTIDES LA English DT Article DE Endotoxin; Ghrelin; Nucleobindin2; Stomach; X/A-like cell ID REGULATED TRANSCRIPT PEPTIDE; EDINGER-WESTPHAL NUCLEUS; FASTED PLASMA GHRELIN; FOOD-INTAKE; NESFATIN-1 NEURONS; BODY-WEIGHT; IMMUNOREACTIVITY; BRAIN; EXPRESSION; RECEPTOR AB Bacterial lipopolysaccharide (LPS) is an established animal model to study the innate immune response to Gram-negative bacteria mimicking symptoms of infection including reduction of food intake. LPS decreases acyl ghrelin associated with decreased concentrations of circulating ghrelin-O-acyltransferase (GOAT) likely contributing to the anorexigenic effect. We also recently described the prominent expression of the novel anorexigenic hormone, nucleobindin2 (NUCB2)/nesfatin-1 in gastric X/A-like cells co-localized with ghrelin in different pools of vesicles. To investigate whether LPS would affect gastric and circulating NUCB2/nesfatin-1 concentration, ad libitum fed rats were equipped with an intravenous (iv) catheter. LPS was injected intraperitoneally (ip, 100 mu g/kg) and blood was withdrawn before and at 2, 5, 7 and 24 h post injection and processed for NUCB2/nesfatin-1 radioimmunoassay. Gastric corpus was collected to measure NUCB2 mRNA expression by RT-qPCR and NUCB2/nesfatin-1 protein concentration by Western blot. Injection of LPS increased plasma NUCB2/nesfatin-1 concentrations by 43%, 78% and 62% compared to vehicle at 2 h, 5 h and 7 h post injection respectively (p < 0.05) and returned to baseline at 24 h. The plasma NUCB2/nesfatin-1 increase at 2 h was associated with increased corpus NUCB2 mRNA expression (p < 0.01), whereas NUCB2 mRNA was not detectable in white blood cells. Likewise, gastric NUCB2 protein concentration was increased by 62% after LPS compared to vehicle (p < 0.01). These data show that gastric NUCB2 production and release are increased in response to LPS. These changes are opposite to those of ghrelin in response to LPS supporting a differential gastric regulation of NUCB2/nesfatin-1 and ghrelin expression derived from the same cell by immune challenge. (C) 2011 Published by Elsevier Inc. C1 [Stengel, Andreas; Goebel-Stengel, Miriam; Tache, Yvette] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress, Dept Med,Digest Dis Div, Los Angeles, CA 90073 USA. [Stengel, Andreas; Goebel-Stengel, Miriam; Tache, Yvette] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. [Stengel, Andreas; Kobelt, Peter] Univ Med Berlin, Dept Med, Div Psychosomat Med & Psychotherapy, Charite, Berlin, Germany. [Goebel-Stengel, Miriam] Martin Luther Krankenhaus, Dept Med, Berlin, Germany. [Goebel-Stengel, Miriam] Martin Luther Krankenhaus, Inst Neurogastroenterol, Berlin, Germany. [Lambrecht, Nils W. G.] Vet Affairs Long Beach Healthcare Syst, Gastrointestinal Endocrinol, Long Beach, CA 90822 USA. RP Lambrecht, NWG (reprint author), VA Long Beach HCS, 5901 E 7th St,Bldg 1,Rm 200M, Long Beach, CA 90822 USA. EM Nils.Lambrecht2@va.gov OI Lambrecht, Nils/0000-0002-1275-1384 FU Department of Veterans Affairs; VA Research Career Scientist Award; NIH [DK-33061]; Center [DK-41301] FX This work was supported by Department of Veterans Affairs Merit Awards (N.W.G.L. and Y.T.), VA Research Career Scientist Award (Y.T.), NIH DK-33061 (Y.T.) and Center grant DK-41301 (Animal Core, Y.T.). NR 45 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PD SEP PY 2011 VL 32 IS 9 BP 1942 EP 1947 DI 10.1016/j.peptides.2011.07.006 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 831YQ UT WOS:000295767400022 PM 21782869 ER PT J AU Liu, CT Garnaas, MK Tin, A Kottgen, A Franceschini, N Peralta, CA de Boer, IH Lu, XN Atkinson, E Ding, JZ Nalls, M Shriner, D Coresh, J Kutlar, A Bibbins-Domingo, K Siscovick, D Akylbekova, E Wyatt, S Astor, B Mychaleckjy, J Li, M Reilly, MP Townsend, RR Adeyemo, A Zonderman, AB de Andrade, M Turner, ST Mosley, TH Harris, TB Rotimi, CN Liu, YM Kardia, SLR Evans, MK Shlipak, MG Kramer, H Flessner, MF Dreisbach, AW Goessling, W Cupples, LA Kao, WL Fox, CS AF Liu, Ching-Ti Garnaas, Maija K. Tin, Adrienne Kottgen, Anna Franceschini, Nora Peralta, Carmen A. de Boer, Ian H. Lu, Xiaoning Atkinson, Elizabeth Ding, Jingzhong Nalls, Michael Shriner, Daniel Coresh, Josef Kutlar, Abdullah Bibbins-Domingo, Kirsten Siscovick, David Akylbekova, Ermeg Wyatt, Sharon Astor, Brad Mychaleckjy, Josef Li, Man Reilly, Muredach P. Townsend, Raymond R. Adeyemo, Adebowale Zonderman, Alan B. de Andrade, Mariza Turner, Stephen T. Mosley, Thomas H. Harris, Tamara B. Rotimi, Charles N. Liu, Yongmei Kardia, Sharon L. R. Evans, Michele K. Shlipak, Michael G. Kramer, Holly Flessner, Michael F. Dreisbach, Albert W. Goessling, Wolfram Cupples, L. Adrienne Kao, W. Linda Fox, Caroline S. CA CKDGen Consortium TI Genetic Association for Renal Traits among Participants of African Ancestry Reveals New Loci for Renal Function SO PLOS GENETICS LA English DT Article ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; DIABETIC-NEPHROPATHY; UNITED-STATES; ZEBRAFISH; POPULATIONS; PROGRESSION; SUSCEPTIBILITY; PREDICTORS; MUTATIONS AB Chronic kidney disease (CKD) is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA), and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR), CKD (eGFR,60 mL/min/1.73 m(2)), urinary albumin-to-creatinine ratio (UACR), and microalbuminuria (UACR>30 mg/g) and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B). Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3). In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3x10(-7)) and FNDC1 (p-value = 3.0x10(-7)) for UACR, and KCNQ1 with eGFR (p = 3.6x10(-6)). Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish. C1 [Liu, Ching-Ti; Lu, Xiaoning; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Garnaas, Maija K.; Goessling, Wolfram] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Garnaas, Maija K.; Goessling, Wolfram; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Garnaas, Maija K.; Goessling, Wolfram; Kao, W. Linda] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Tin, Adrienne; Kottgen, Anna; Li, Man] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Kottgen, Anna] Univ Hosp Freiburg, Div Renal, Freiburg, Germany. [Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Peralta, Carmen A.] Univ Calif San Francisco, Sch Med, Div Nephrol, San Francisco, CA USA. [Peralta, Carmen A.] San Francisco VA Med Ctr, San Francisco, CA USA. [de Boer, Ian H.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [de Boer, Ian H.] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Atkinson, Elizabeth; de Andrade, Mariza] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA. [Ding, Jingzhong] Wake Forest Univ Hlth Sci, J Paul Sticht Ctr Aging, Winston Salem, NC USA. [Nalls, Michael] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Shriner, Daniel; Adeyemo, Adebowale; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. [Coresh, Josef] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Kutlar, Abdullah] Med Coll Georgia, Augusta, GA 30912 USA. [Siscovick, David] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Siscovick, David] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Akylbekova, Ermeg] Jackson State Univ, Jackson, MS USA. [Wyatt, Sharon] Univ Mississippi, Med Ctr, Sch Nursing, Jackson, MS 39216 USA. [Astor, Brad] Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Mychaleckjy, Josef] Ctr Publ Hlth Genom, Charlottesville, VA USA. [Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Townsend, Raymond R.] Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. [Zonderman, Alan B.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. [Turner, Stephen T.] Mayo Clin, Div Nephrol & Hypertens, Dept Internal Med, Rochester, MN USA. [Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr, Jackson, MS 39216 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Liu, Yongmei] Wake Forest Univ, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. [Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Evans, Michele K.] NIA, Hlth Dispar Res Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Kramer, Holly] Loyola Univ, Maywood, IL 60153 USA. [Flessner, Michael F.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA. [Dreisbach, Albert W.] Univ Mississippi, Div Nephrol, Jackson, MS 39216 USA. [Goessling, Wolfram] Brigham & Womens Hosp, Dept Med, Div Gastroenterol, Boston, MA 02115 USA. [Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Boston, MA USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Liu, CT (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. EM wgoessling@partners.org; wkao@jhsph.edu; foxca@nhlbi.nih.gov RI Kottgen, Anna/D-2920-2012 OI Cupples, L. Adrienne/0000-0003-0273-7965; Kramer, Holly/0000-0002-6374-837X; Adeyemo, Adebowale/0000-0002-3105-3231; Goessling, Wolfram/0000-0001-9972-1569; Zonderman, Alan B/0000-0002-6523-4778 FU NHLBI [R01-HL087660]; NIA [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]; National Institutes of Health [HHSN268200782096C, S06GM008016-320107, S06GM008016-380111, 2M01RR010284]; NIH, National Institute on Aging. Howard University Family Study; Center for Research on Genomics and Global Health; National Human Genome Research Institute; National Institute of Diabetes and Digestive and Kidney Diseases; Center for Information Technology; Office of the Director at the National Institutes of Health [Z01HG200362]; NIH, National Institute on Aging; National Center on Minority Health and Health Disparities [Z01-AG000513, 2009-149]; National Heart, Lung, and Blood Institute FX The following nine parent studies have contributed parent study data, ancillary study data, and DNA samples through the Massachusetts Institute of Technology - Broad Institute (N01-HC-65226) to create this genotype/phenotype data base for wide dissemination to the biomedical research community: Atherosclerotic Risk in Communities (ARIC): University of North Carolina at Chapel Hill (N01-HC-55015), Baylor Medical College (N01-HC-55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas Houston (N01-HC-55022), University of North Carolina Forsyth County (N01-HC-55018); Cardiovascular Health Study (CHS): University of Washington (N01-HC-85079), Wake Forest University (N01-HC-85080), Johns Hopkins University (N01-HC-85081), University of Pittsburgh (N01-HC-85082), University of California Davis (N01-HC-85083), University of California Irvine (N01-HC-85084), New England Medical Center (N01-HC-85085), University of Vermont (N01-HC-85086), Georgetown University (N01-HC-35129), Johns Hopkins University (N01 HC-15103), University of Wisconsin (N01-HC-75150), Geisinger Clinic (N01-HC-45133), University of Washington (N01 HC-55222, U01 HL080295); Cleveland Family Study (CFS): Case Western Reserve University (NIH HL 46380, M01RR00080); Cooperative Study of Sickle Cell Disease (CSSCD): University of Illinois (N01-HB-72982, N01-HB-97062), Howard University (N01-HB-72991, N01-HB-97061), University of Miami (N01-HB-72992, N01-HB-97064), Duke University (N01-HB-72993), George Washington University (N01-HB-72994), University of Tennessee (N01-HB-72995, N01-HB-97070), Yale University (N01-HB-72996, N01-HB-97072), Children's Hospital-Philadelphia (N01-HB-72997, N01-HB-97056), University of Chicago (N01-HB-72998, N01-HB-97053), Medical College of Georgia (N01-HB-73000, N01-HB-97060), Washington University (N01-HB-73001, N01-HB-97071), Jewish Hospital and Medical Center of Brooklyn (N01-HB-73002), Trustees of Health and Hospitals of the City of Boston (N01-HB-73003), Children's Hospital-Oakland (N01-HB-73004, N01-HB-97054), University of Mississippi (N01-HB-73005), St. Luke's Hospital-New York (N01-HB-73006), Alta Bates-Herrick Hospital (N01-HB-97051), Columbia University (N01-HB97058), St.; Jude's Children's Research Hospital (N01-HB-97066), Research Foundation of the State University of New York-Albany (N01-HB-97068, N01-HB-97069), New England Research Institute (N01-HB-97073), Interfaith Medical Center-Brooklyn (N01-HB-97085); Coronary Artery Risk in Young Adults (CARDIA): University of Alabama at Birmingham (N01-HC-48047), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), University of Alabama at Birmingham (N01-HC-95095), Tufts-New England Medical Center (N01-HC-45204), Wake Forest University (N01-HC45205), Harbor-UCLA Research and Education Institute (N01-HC-05187), University of California Irvine (N01-HC-45134, N01-HC-95100); Framingham Heart Study (FHS): Boston University (N01-HC-25195, R01HL092577-01A1, RO1 HL076784, R01 AG028321); Jackson Heart Study (JHS): Jackson State University (N01-HC-95170), University of Mississippi (N01-HC-95171), Tougaloo College (N01-HC-95172); Multi-Ethnic Study of Atherosclerosis (MESA): University of Washington (N01-HC-95159), Regents of the University of California (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162, N01-HC-95168), University of Minnesota (N01-HC-95163), Northwestern Universiy (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC-95166), New England Medical Center (N01-HC-95167), Harbor-UCLA Research and Education Institute (N01-HC-95169), Cedars-Sinai Medical Center (R01-HL-071205), University of Virginia (subcontract to R01-HL-071205); Sleep Heart Health Study (SHHS): Johns Hopkins University (U01 HL064360), Case Western University (U01 HL063463), University of California, Davis (U01 HL053916), University of Arizona (U01 HL053938), University of Minnesota (relocating in 2006 to Univ Arizona) (U01 HL053934), University of Pittsburgh (U01 HL077813), Boston University (U01 HL053941), MedStar Research Institute (U01 HL063429), Johns Hopkins University (U01 HL053937). GENOA: The GENOA Study genome-wide association study was funded by NHLBI R01-HL087660. HABC: This research was supported by NIA contracts N01AG62101, N01AG62103, and N01AG62106. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Howard University Family Study: The Howard University Family Study was supported by National Institutes of Health grants S06GM008016-320107 and S06GM008016-380111. Enrollment was carried out at the Howard University General Clinical Research Center, supported by National Institutes of Health grant 2M01RR010284. This research was supported in part by the Intramural Research Program of the Center for Research on Genomics and Global Health. The Center for Research on Genomics and Global Health is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (Z01HG200362). Genotyping support was provided by the Coriell Institute for Medical Research. We thank the participants of the Howard University Family Study.; The contents of this publicationare solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health. HANDLS: This research was supported by the Intramural Research Program of the NIH, National Institute on Aging and the National Center on Minority Health and Health Disparities (Intramural Project # Z01-AG000513 and human subjects protocol # 2009-149). Data analyses for the HANDLS study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD. (http://biowulf.nih.gov). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; The authors wish to acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the research institutions, study investigators, field staff, and study participants in creating this resource for biomedical research. The authors wish to thank Andrea Calhoun and Dr. Susan Hagen at the Electron Microscopy Core Facility at Beth Israel Deaconess Medical Center for expert assistance with electron microscopy and Drs. Dirk Hentschel and Helmut Rennke at Brigham and Women's Hospital for advice on electron microscopy images. We thank Dr. Iain Drummond at Massachusetts General Hospital and Dr. Rebecca Wingert at the University of Notre Dame for in situ probes. NR 42 TC 60 Z9 61 U1 2 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD SEP PY 2011 VL 7 IS 9 AR e1002264 DI 10.1371/journal.pgen.1002264 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 827HH UT WOS:000295419100018 PM 21931561 ER PT J AU Hagan, MP Saleh, H Moore, M Williamson, J AF Hagan, Michael P. Saleh, Habeeb Moore, Mary Williamson, Jeffrey TI Regulatory evaluation of prostate volume implants: Pitfalls of a retrospective assessment SO BRACHYTHERAPY LA English DT Article DE Prostate; Brachytherapy; Volume implant; Evaluation; Medical event ID POSTIMPLANT DOSIMETRY; COMPUTED-TOMOGRAPHY; TREATMENT DELIVERY; SEED LOCALIZATION; BRACHYTHERAPY; ULTRASOUND; CANCER; EDEMA; RECOMMENDATIONS; QUALITY AB PURPOSE: Evaluate for regulatory compliance the prostate implants from the Philadelphia Veterans Medical Center applying both an activity-based and volume-corrected D(90) (the maximum dose delivered to 90% of the prostate volume) metrics. METHODS AND MATERIALS: Dosimetry from 107 prostate implants performed at the Philadelphia Veterans Medical Center used immediate postprocedural CT image sets. D(90) values were adjusted for volume differences from planning volumes. Medical events (MEs) determined from the volume-corrected data were compared with an activity-based metric. RESULTS: Examination of images using original and third-party reviewed prostate contours revealed 56 and 62 cases with D(90) values <80% of the prescription close, respectively. Because postprocedural prostate volumes were on average 55.7% larger than the planned volume, clinical nomogram-based doses using the implanted activity and actual volumes found 34-47 implants failing to achieve closes greater than 80% of the prescription dose. Volume correction identified 20 MEs, 9 cases with D(90) values within 4% of the ME threshold and 11 significantly inferior cases with median D(90) values <52% of the prescribed dose. Eleven implants also had 20% or more seeds beyond the treatment site according to an activity metric recommended by the VHA Blue Ribbon Panel. Ten of these 11 cases were also identified by volume-corrected D(90) metric. The remaining 96 cases, however, had 95% (+/-6%) of seeds placed within the treatment site. CONCLUSIONS: Of the cases reported to the United States Nuclear Regulatory Commission (NRC) on the basis of Day-1 D(90) values, many appear to have been acceptable implants relative to standard-of-practice clinical criteria. The activity-based dose metric, endorsed by the NRC Advisory Committee on the Medical Uses of Isotopes in 2005 and recommended by the VHA Blue Ribbon Panel for Prostate Brachytherapy yields a more robust determination of ME for this population of implants. Published by Elsevier Inc. All rights reserved. C1 [Hagan, Michael P.; Saleh, Habeeb; Williamson, Jeffrey] Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA 23298 USA. [Hagan, Michael P.] Vet Hlth Agcy, Dept Vet Affairs, Natl Radiat Oncol Program Off, Richmond, VA USA. [Moore, Mary] Philadelphia VA Med Ctr, Radiat Safety Off, Philadelphia, PA USA. RP Hagan, MP (reprint author), Virginia Commonwealth Univ, Dept Radiat Oncol, 401 Coll St, Richmond, VA 23298 USA. EM michael.hagan@va.gov NR 35 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 J9 BRACHYTHERAPY JI Brachytherapy PD SEP-OCT PY 2011 VL 10 IS 5 BP 385 EP 394 DI 10.1016/j.brachy.2011.01.005 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 826IB UT WOS:000295346700007 PM 21349777 ER PT J AU Ibarra, JM Quinones, MP Estrada, CA Jimenez, F Martinez, HG Ahuja, SS AF Ibarra, Jessica M. Quinones, Marlon P. Estrada, Carlos A. Jimenez, Fabio Martinez, Hernan G. Ahuja, Seema S. TI CD8 alpha(+) dendritic cells improve collagen-induced arthritis in CC chemokine receptor (CCR)-2 deficient mice SO IMMUNOBIOLOGY LA English DT Article DE CCR2; Dendritic cells; CD8 alpha(+) DC; Arthritis; SKG ID REGULATORY T-CELLS; RHEUMATOID-ARTHRITIS; AUTOIMMUNE ARTHRITIS; TRANSPLANT TOLERANCE; DIFFERENT MECHANISMS; LEISHMANIA-MAJOR; LIGAND; DIFFERENTIATION; CYTOKINES; RESPONSES AB Objective: Dendritic cells (DCs) have long been recognized as potential therapeutic targets of rheumatoid arthritis (RA). Increasing evidence has showed that DCs are capable of suppressing autoimmunity by expanding FoxP3(+) regulatory T cells (T g), which in turn exert immunosuppression by increasing TGF beta-1. In the SKG mice, activated DC prime autoreactive T cells causing autoantibody production and an inflammatory arthritic response. Recently, we reported that CC-chemokine receptor-2 deficient (Ccr2(-/-)) mice had impaired DCs migration and reduced CD8 alpha(+) DCs in the C57B1/6J mice strain and that these mice were more susceptible to collagen antibody-induced arthritis (CAIA), compared to wild type mice. To examine the mechanism by which DCs contribute to the increased susceptibility of arthritis in Ccr2(-/-)mice, we tested the hypothesis that CD8 alpha(+) DCs are protective (tolerogenic) against autoimmune arthritis by examining the role of CD8 alpha(+) DCs in Ccr2(-/-) and SKG mice. Methods: To examine the mechanism by which DCs defects lead to the development of arthritis, we used two murine models of experimental arthritis: collagen-induced arthritis (CIA) in DBA1/J mice and zymosan-induced arthritis in SKG mice. DBA1/J mice received recombinant fms-like tyrosine kinase 3 ligand (Flt3L) injections to expand endogenous DCs populations or adoptive transfers of CD8 alpha(+) DCs. Results: Flt3L-mediated expansion of endogenous CD8 alpha(+) DCs resulted in heightened susceptibility of CIA. In contrast, supplementation with exogenous CD8 alpha(+) DCs ameliorated arthritis in Ccr2(-/-) mice and enhanced TGF beta 1 production by T cells. Furthermore, SKG mice with genetic inactivation of CCR2 did not affect the numbers of DCs nor improve the arthritis phenotype. Conclusion: CD8 alpha(+) DCs were tolerogenic to the development of arthritis. CD8 alpha(+) DCs deficiency heightened the sensitivity to arthritis in Ccr2(-/-) mice. Ccr2 deficiency did not alter the arthritic phenotype in SKG mice suggesting the arthritis in Ccr2(-/-) mice was T cell-independent. Published by Elsevier GmbH. C1 [Ibarra, Jessica M.; Quinones, Marlon P.; Estrada, Carlos A.; Jimenez, Fabio; Martinez, Hernan G.; Ahuja, Seema S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Quinones, Marlon P.; Estrada, Carlos A.; Jimenez, Fabio; Martinez, Hernan G.; Ahuja, Seema S.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, Vet Adm Ctr Res AIDS & HIV Infect 1, San Antonio, TX USA. RP Ahuja, SS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, MC7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM ahuja@uthscsa.edu FU National Institutes of Health (NIH) [AI48644, AR052755] FX This work was supported in part by the National Institutes of Health (NIH)grants (AI48644 and AR052755) and VA Merit to S.S.A. NR 30 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD SEP PY 2011 VL 216 IS 9 BP 971 EP 978 DI 10.1016/j.imbio.2011.03.012 PG 8 WC Immunology SC Immunology GA 829TG UT WOS:000295606600001 PM 21531476 ER PT J AU Parikh, CR Devarajan, P Zappitelli, M Sint, K Thiessen-Philbrook, H Li, S Kim, RW Koyner, JL Coca, SG Edelstein, CL Shlipak, MG Garg, AX Krawczeski, CD AF Parikh, Chirag R. Devarajan, Prasad Zappitelli, Michael Sint, Kyaw Thiessen-Philbrook, Heather Li, Simon Kim, Richard W. Koyner, Jay L. Coca, Steven G. Edelstein, Charles L. Shlipak, Michael G. Garg, Amit X. Krawczeski, Catherine D. CA TRIBE-AKI Consortium TI Postoperative Biomarkers Predict Acute Kidney Injury and Poor Outcomes after Pediatric Cardiac Surgery SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GELATINASE-ASSOCIATED LIPOCALIN; ACUTE-RENAL-FAILURE; CONGENITAL HEART-DISEASE; ROC CURVE; NGAL; CHILDREN; MARKERS; INCREASES; DIALYSIS; THERAPY AB Acute kidney injury (AKI) occurs commonly after pediatric cardiac surgery and associates with poor outcomes. Biomarkers may help the prediction or early identification of AKI, potentially increasing opportunities for therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 311 children undergoing surgery for congenital cardiac lesions to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. Severe AKI, defined by dialysis or doubling in serum creatinine during hospital stay, occurred in 53 participants at a median of 2 days after surgery. The first postoperative urine IL-18 and urine NGAL levels strongly associated with severe AKI. After multivariable adjustment, the highest quintiles of urine IL-18 and urine NGAL associated with 6.9- and 4.1-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine NGAL levels associated with longer hospital stay, longer intensive care unit stay, and duration of mechanical ventilation. The accuracy of urine IL-18 and urine NGAL for diagnosis of severe AKI was moderate, with areas under the curve of 0.72 and 0.71, respectively. The addition of these urine biomarkers improved risk prediction over clinical models alone as measured by net reclassification improvement and integrated discrimination improvement. In conclusion, urine IL-18 and urine NGAL, but not plasma NGAL, associate with subsequent AKI and poor outcomes among children undergoing cardiac surgery. C1 [Parikh, Chirag R.; Sint, Kyaw; Coca, Steven G.] Yale Univ, Sch Med, Nephrol Sect, New Haven, CT USA. [Parikh, Chirag R.; Sint, Kyaw; Coca, Steven G.] Vet Affairs Med Ctr, Clin Epidemiol Res Ctr, West Haven, CT 06516 USA. [Devarajan, Prasad; Krawczeski, Catherine D.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Zappitelli, Michael] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Pediat,Div Nephrol, Montreal, PQ H3H 1P3, Canada. [Thiessen-Philbrook, Heather; Garg, Amit X.] Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada. [Li, Simon] Yale Univ, Sch Med, Dept Pediat, Div Pediat Crit Care Med, New Haven, CT 06510 USA. [Kim, Richard W.] Yale Univ, Sch Med, Div Pediat Cardiac Surg, New Haven, CT USA. [Koyner, Jay L.] Univ Chicago, Pritzker Sch Med, Dept Med, Nephrol Sect, Chicago, IL 60637 USA. [Edelstein, Charles L.] Univ Colorado, Div Renal Dis, Denver, CO 80202 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Parikh, CR (reprint author), Yale Univ, Nephrol Sect, 950 Campbell Ave,Mail Code 151B,Bldg 35 A,Room 21, West Haven, CT 06516 USA. EM chirag.parikh@yale.edu OI Wang, Zhu/0000-0002-0773-0052 FU American Heart Association; National Heart, Lung, and Blood Institute [R01 HL-085757]; National Center for Research Resources [UL1 RR024139] FX The research reported in this article was supported by the American Heart Association Clinical Development Award, Grant R01 HL-085757 from the National Heart, Lung, and Blood Institute. The study was also supported by CTSA Grant Number UL1 RR024139 from the National Center for Research Resources. This work is Clinical Trials.gov number NCT00774137. The urine biomarker assays were donated by Abbott Diagnostics. Plasma NGAL was donated by Biosite, Inc. NR 36 TC 142 Z9 143 U1 0 U2 7 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2011 VL 22 IS 9 BP 1737 EP 1747 DI 10.1681/ASN.2010111163 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 831CH UT WOS:000295705800021 PM 21836147 ER PT J AU Parikh, CR Coca, SG Thiessen-Philbrook, H Shlipak, MG Koyner, JL Wang, Z Edelstein, CL Devarajan, P Patel, UD Zappitelli, M Krawczeski, CD Passik, CS Swaminathan, M Garg, AX AF Parikh, Chirag R. Coca, Steven G. Thiessen-Philbrook, Heather Shlipak, Michael G. Koyner, Jay L. Wang, Zhu Edelstein, Charles L. Devarajan, Prasad Patel, Uptal D. Zappitelli, Michael Krawczeski, Catherine D. Passik, Cary S. Swaminathan, Madhav Garg, Amit X. CA TRIBE-AKI Consortium TI Postoperative Biomarkers Predict Acute Kidney Injury and Poor Outcomes after Adult Cardiac Surgery SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GELATINASE-ASSOCIATED LIPOCALIN; ACUTE-RENAL-FAILURE; ACUTE CORONARY SYNDROMES; MORTALITY; RISK; RECLASSIFICATION; ASSOCIATION; DYSFUNCTION; MARKERS; MICE AB Acute kidney injury (AKI) is a frequent complication of cardiac surgery and increases morbidity and mortality. The identification of reliable biomarkers that allow earlier diagnosis of AKI in the postoperative period may increase the success of therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 1219 adults undergoing cardiac surgery to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse patient outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. After multivariable adjustment, the highest quintiles of urine IL-18 and plasma NGAL associated with 6.8-fold and 5-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine and plasma NGAL levels associated with longer length of hospital stay, longer intensive care unit stay, and higher risk for dialysis or death. The clinical prediction model for AKI had an area under the receiver-operating characteristic curve (AUC) of 0.69. Urine IL-18 and plasma NGAL significantly improved the AUC to 0.76 and 0.75, respectively. Urine IL-18 and plasma NGAL significantly improved risk prediction over the clinical models alone as measured by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). In conclusion, urine IL-18, urine NGAL, and plasma NGAL associate with subsequent AKI and poor outcomes among adults undergoing cardiac surgery. (Clinical Trials.gov number, NCT00774137). C1 [Parikh, Chirag R.; Coca, Steven G.; Wang, Zhu] Yale Univ, Sch Med, Nephrol Sect, New Haven, CT USA. [Parikh, Chirag R.; Coca, Steven G.; Wang, Zhu] Vet Affairs Med Ctr, Clin Epidemiol Res Ctr, West Haven, CT USA. [Thiessen-Philbrook, Heather; Garg, Amit X.] Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada. [Shlipak, Michael G.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Vet Adm Med Ctr, San Francisco, CA 94143 USA. [Koyner, Jay L.] Univ Chicago, Pritzker Sch Med, Dept Med, Nephrol Sect, Chicago, IL 60637 USA. [Edelstein, Charles L.] Univ Colorado, Div Renal Dis, Denver, CO 80202 USA. [Devarajan, Prasad; Krawczeski, Catherine D.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Patel, Uptal D.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Swaminathan, Madhav] Duke Univ, Sch Med, Dept Anesthesiol, Div Cardiothorac Anesthesiol & Crit Care Med, Durham, NC USA. [Zappitelli, Michael] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Pediat,Div Nephrol, Montreal, PQ H3H 1P3, Canada. [Passik, Cary S.] Danbury Hosp, Dept Cardiothorac Surg, Danbury, CT USA. [Passik, Cary S.] Univ Vermont, Coll Med, Burlington, VT USA. RP Parikh, CR (reprint author), Yale Univ, Nephrol Sect, 950 Campbell Ave,Mail Code 151B,Bldg 35 A,Room 21, West Haven, CT 06516 USA. EM chirag.parikh@yale.edu FU American Heart Association from the National Heart, Lung, and Blood Institute [R01 HL-085757]; National Center for Research Resources [UL1 RR024139]; Abbott Diagnostics; Biosite, Inc. FX We would also like to thank the nursing and support staff of the preadmission clinic, anesthesia units, and the cardiac care units at all of the participating centers. The research reported in this article was supported by the American Heart Association Clinical Development award (grant R01 HL-085757) from the National Heart, Lung, and Blood Institute. The study was also supported by a Clinical and Translational Science Award grant (UL1 RR024139) from the National Center for Research Resources. The urine biomarker assays were donated by Abbott Diagnostics, and plasma NGAL was donated by Biosite. The granting agencies, Abbott Diagnostics and Biosite, Inc., did not participate in the protocol development, analysis, or interpretation of the results. NR 36 TC 191 Z9 193 U1 0 U2 11 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 SEP PY 2011 VL 22 IS 9 BP 1748 EP 1757 DI 10.1681/ASN.2010121302 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 831CH UT WOS:000295705800022 PM 21836143 ER PT J AU Vladutiu, GD Isackson, PJ Kaufman, K Harley, JB Cobb, B Christopher-Stine, L Wortmann, RL AF Vladutiu, Georgirene D. Isackson, Paul J. Kaufman, Kenneth Harley, John B. Cobb, Beth Christopher-Stine, Lisa Wortmann, Robert L. TI Genetic risk for malignant hyperthermia in non-anesthesia-induced myopathies SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Malignant hyperthermia; Statin myopathy; RYR1 gene mutations; Metabolic muscle disease; Coexisting genetic risk ID DEPENDENT CALCIUM-CHANNEL; CENTRAL CORE DISEASE; SKELETAL-MUSCLE; RYANODINE RECEPTOR; EXERTIONAL RHABDOMYOLYSIS; SUSCEPTIBILITY LOCUS; CONGENITAL MYOPATHY; MOLECULAR-BASIS; RYR1 MUTATIONS; FAMILIES AB Malignant hyperthermia (MH) is a pharmacogenetic, autosomal dominantly inherited disorder of skeletal muscle triggered by volatile anesthetics and infrequently by extreme exertion and heat exposure. MH has variable penetrance with an incidence ranging from 1 in 5000 to 1 in 50,000-100,000 anesthesias. Mutations in the ryanodine receptor gene, RYR1, are found in 50-70% of cases. We hypothesized that a portion of patients with drug-induced muscle diseases, unrelated to anesthesia, such as severe statin myopathy, have underlying genetic liability that may include RYR1 gene mutations. DNA samples were collected from 885 patients in 4 groups: severe statin myopathy (n = 197), mild statin myopathy (n = 163), statin-tolerant controls (n = 133), and non-drug-induced myopathies of unknown etiology characterized by exercise-induced muscle pain and weakness (n = 392). Samples were screened for 105 mutations and variants in 26 genes associated with 7 categories of muscle disease including 34 mutations and variants in the RYR1 gene. Disease-causing mutations or variants in RYR1 were present in 3 severe statin myopathy cases, 1 mild statin myopathy case, 8 patients with non-drug-induced myopathy, and none in controls. These results suggest that disease-causing mutations and certain variants in the RYR1 gene may contribute to underlying genetic risk for non-anesthesia-induced myopathies and should be included in genetic susceptibility screening in patients with severe statin myopathy and in patients with non-statin-induced myopathies of unknown etiology. (C) 2011 Elsevier Inc. All rights reserved. C1 [Vladutiu, Georgirene D.; Isackson, Paul J.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Pediat, Buffalo, NY 14203 USA. [Vladutiu, Georgirene D.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Neurol, Buffalo, NY 14203 USA. [Vladutiu, Georgirene D.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Pathol & Anat Sci, Buffalo, NY 14203 USA. [Kaufman, Kenneth] Univ Oklahoma, Oklahoma Med Res Fdn, Hlth Sci Ctr, Oklahoma City, OK USA. [Kaufman, Kenneth] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Harley, John B.; Cobb, Beth] Cincinnati Childrens Hosp, Dept Med, Cincinnati, OH USA. [Christopher-Stine, Lisa] Johns Hopkins Univ, Dept Med, Johns Hopkins Sch Med, Myositis Ctr, Baltimore, MD USA. [Wortmann, Robert L.] Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA. RP Vladutiu, GD (reprint author), SUNY Buffalo, Sch Med & Biomed Sci, Dept Pediat, 100 High St, Buffalo, NY 14203 USA. EM gdv@buffalo.edu FU NHLBI [1R41HL093956-01, RO1HL085800]; UB Office of the Vice President for Research FX This work was supported by grants from the NHLBI (1R41HL093956-01 and RO1HL085800; GDV) and an Interdisciplinary Research and Creative Activities Award from the UB Office of the Vice President for Research (GDV). We are especially grateful to Dr. Nyamkhishig Sambuughin for her assistance in the interpretation of RYR1 gene variant data. We thank Dr. Henry Rosenberg for his helpful comments during the preparation of this manuscript. We thank Ms. Shanping Huang for technical assistance with preparation, organization and individual genotyping of genomic DNA samples and Ms. Catherine Kern for coordination of collaborating centers and maintenance of the participant database. We also are grateful to physicians and their patients from medical centers including the Mayo Clinic, Rochester, MN; Cedars Sinai Medical Center, Los Angeles, CA; Texas Children's Hospital, Houston, TX; Walter Reed Army Medical Center, Washington, DC; the Oregon Health 8: Science University, Portland, OR; Yale-New Haven Medical Center, New Haven, CT; McMaster University, Hamilton, Ontario, Canada; and the VA Western New York Healthcare System, Buffalo, NY. NR 38 TC 24 Z9 24 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2011 VL 104 IS 1-2 SI SI BP 167 EP 173 DI 10.1016/j.ymgme.2011.07.001 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 823UF UT WOS:000295151300027 PM 21795085 ER PT J AU Arar, N Seo, J Abboud, HE Parchman, M Noel, P AF Arar, Nedal Seo, Joann Abboud, Hanna E. Parchman, Michael Noel, Polly TI Veterans' experience in using the online Surgeon General's family health history tool SO PERSONALIZED MEDICINE LA English DT Article DE family health history; genomic services; Surgeon General's online tool ID GENOMIC MEDICINE; PRIMARY-CARE; SATISFACTION; INFORMATION; DISEASE; POPULATION; PREVENTION; COMMUNITY; INTERNET; DELIVERY AB Aim: To assess veterans' experience and satisfaction in using the Surgeon General's (SG) online family health history (FHH) tool, and determine the perceived facilitators and barriers to using the online SG-FHH tool. Materials & methods: A mixed-method using both qualitative and quantitative approaches was employed in this study. A total of 35 veterans at the VA Medical Center in San Antonio, Texas, USA were invited to enter their FHH information using the online SG-FHH tool, complete the study's satisfaction survey and participate in a short semi-structured interview. The goal of the semi-structured interviews was to assess participants perceived facilitators and barriers to using the online SG-FHH tool. All participants were also provided with a printed copy of their pedigree, which was generated by the SG-FHH tool and were encouraged to share it with their relatives and providers. Results: The majority of participants (91%) said that they had access to a computer with internet capability and 77% reported that they knew how to use a computer. More than two-thirds of the participants felt that items on the SG-FHH tool were easy to read and felt that FHH categories were relevant to their family's health. Approximately 94% of participants viewed the SG-FHH tool as useful, and the majority of participants (97%) indicated that they were likely to recommend the tool to others. Content analysis of the semi-structured interviews highlighted several barriers to veterans' use of the SG-FHH tool and their FHH information. These included: lack of patients' knowledge regarding their relatives' FHH, and privacy and confidentiality concerns. Conclusion: This study provides information on the performance and functionality of an inexpensive and widely accessible method for FHH collection. Furthermore, our findings highlight several opportunities and challenges facing the utilization of FHH information as a clinical and genomic tool at the Veterans Health Administration (VHA). The results suggest that strategies that improve veterans' knowledge regarding the importance of their FHH information and that address their concerns about privacy and confidentiality may enhance the successful implementation of FHH information into VHA clinical practice. Implications: identifying a locally accepted method for FHH collection and documentation which can be conducted outside of the patient visit will reduce time burdens for providers and patients and allow for a focus on other important topics during clinic visits. Improvement in familial risk screening and assessment will enable the VHA to be prepared for personalized medicine and focus their resources on promoting critically important health behaviors for populations with the highest risk of developing chronic diseases and their complications. C1 [Arar, Nedal; Seo, Joann; Abboud, Hanna E.; Parchman, Michael; Noel, Polly] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Arar, Nedal; Seo, Joann; Abboud, Hanna E.; Parchman, Michael; Noel, Polly] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Arar, N (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM ararn@uthscsa.edu OI Parchman, Michael/0000-0001-7129-2889 FU VHA-HSR and D [DNA 08-129, PPO 09-241]; NIH [UL1RR025767] FX This work was supported by the VHA-HSR and D (DNA 08-129 and PPO 09-241, PI: Nedal Arar). This study was partly funded by the Clinical and Translational Science Award (CTSA) - NIH grant (UL1RR025767). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 35 TC 7 Z9 7 U1 1 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD SEP PY 2011 VL 8 IS 5 BP 523 EP 532 DI 10.2217/PME.11.53 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 832JX UT WOS:000295802100010 PM 22076122 ER PT J AU Verma, P Randhawa, I Klaustermeyer, WB AF Verma, Prashant Randhawa, Inderpal Klaustermeyer, William B. TI Clinical efficacy of omalizumab in an elderly veteran population with severe asthma SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article ID SEVERE ALLERGIC-ASTHMA; ANTIIMMUNOGLOBULIN-E THERAPY; SEVERE PERSISTENT ASTHMA; E ANTIBODY OMALIZUMAB; IGE ANTIBODY; ADULTS; EXACERBATIONS; TOLERABILITY; MANAGEMENT; VALIDITY AB Severe asthma in elderly patients is underdiagnosed, difficult to treat, and often accompanied by atopy. This study was designed to compare clinical outcomes of omalizumab therapy in an elderly veteran population with severe allergic asthma. A retrospective, observational data analysis was performed over 2 years. Cohort outcome measures 1 year before omalizumab therapy were compared with 1 year of active treatment. Statistical analysis included two sample t-tests. The total number of patients enrolled was 17 with median age of 60 years. Omalizumab therapy was associated with a significant reduction in acute asthma exacerbations requiring prednisone treatment (p < 0.01), a significant improvement in forced expiratory volume in 1 second of 0.28 L (p < 0.01), and significantly higher Asthma Control Test (ACT) scores at 3 (p = 0.043), 6 (p = 0.039), and 12 months of therapy (p < 0.01). Two of five patients on daily prednisone for >6 months were able to discontinue systemic steroid use within 3 months of omalizumab treatment. Our study suggests elderly patients with severe atopic asthma show a significant positive clinical response to oinalizumab. (Allergy Asthma Proc 32:346-350, 2011; doi: 10.2500/aap.2011.32.3467) C1 [Verma, Prashant; Randhawa, Inderpal; Klaustermeyer, William B.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Med, Div Allergy Immunol, Los Angeles, CA 90073 USA. RP Verma, P (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Med, Div Allergy Immunol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM verma.allergy@gmail.com NR 36 TC 14 Z9 15 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 2011 VL 32 IS 5 BP 346 EP 350 DI 10.2500/aap.2011.32.3467 PG 5 WC Allergy SC Allergy GA 828JN UT WOS:000295497400004 PM 22195686 ER PT J AU Friedman, MJ Resick, PA Bryant, RA Strain, J Horowitz, M Spiegel, D AF Friedman, Matthew J. Resick, Patricia A. Bryant, Richard A. Strain, James Horowitz, Mardi Spiegel, David TI CLASSIFICATION OF TRAUMA AND STRESSOR-RELATED DISORDERS IN DSM-5 SO DEPRESSION AND ANXIETY LA English DT Review DE trauma; stress; stressor; dissociation; dissociative disorders; anxiety disorders; adjustment disorders; PTSD; ASD; posttraumatic stress disorder ID DISSOCIATIVE IDENTITY DISORDER; MENTAL-HEALTH PROBLEMS; COMBAT-RELATED PTSD; POSTTRAUMATIC-STRESS; LIFE EVENTS; PANIC DISORDER; PERITRAUMATIC DISSOCIATION; PSYCHIATRIC OUTPATIENTS; INTERNALIZING SUBTYPES; TERRORIST ATTACKS AB This review examines the question of whether there should be a cluster of disorders, including the adjustment disorders (ADs), acute stress disorder (ASD), posttraumatic stress disorder (PTSD), and the dissociative disorders (DDs), in a section devoted to abnormal responses to stress and trauma in the DSM-5. Environmental risk factors, including the individual's developmental experience, would thus become a major diagnostic consideration. The relationship of these disorders to one another is examined and also their relationship to other anxiety disorders to determine whether they are better grouped with anxiety disorders or a new specific grouping of trauma and stressor-related disorders. First how stress responses have been classified since DSM-III is reviewed. The major focus is on PTSD because it has received the most attention, regarding its proper placement among the psychiatric diagnoses. It is discussed whether PTSD should be considered an anxiety disorder, a stress-induced fear circuitry disorder, an internalizing disorder, or a trauma and stressor-related disorder. Then, ASD, AD, and DD are considered from a similar perspective. Evidence is examined pro and con, and a concision is offered recommending inclusion of this cluster of disorders in a section entitled "Trauma and Stressor-Related Disorders." The recommendation to shift ASD and PTSD out of the anxiety disorders section reflects increased recognition of trauma as a precipitant, emphasizing common etiology over common phenomenology. Similar considerations are addressed with regard to AD and DD. Depression and Anxiety 28:737-749, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Spiegel, David] Dept Psychiat & Behav Sci, Stanford, CA USA. [Friedman, Matthew J.] US Dept Vet Affairs, Natl Ctr PTSD, VA Med Ctr, White River Jct, VT USA. [Friedman, Matthew J.] Dartmouth Med Sch, Dept Psychiat, Hanover, NH USA. [Friedman, Matthew J.] Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH USA. [Resick, Patricia A.] VA Ctr Natl Ctr PTSD, White River Jct, VT USA. [Resick, Patricia A.] Boston Univ, Boston, MA 02215 USA. [Bryant, Richard A.] Univ New S Wales, Sch Psychol, Sydney, NSW, Australia. [Strain, James] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Horowitz, Mardi] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Spiegel, D (reprint author), Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. EM dspiegel@stanford.edu OI Bryant, Richard/0000-0002-9607-819X NR 114 TC 75 Z9 77 U1 11 U2 54 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD SEP PY 2011 VL 28 IS 9 SI SI BP 737 EP 749 DI 10.1002/da.20845 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 823EK UT WOS:000295105100002 PM 21681870 ER PT J AU Strain, JJ Friedman, MJ AF Strain, James J. Friedman, Matthew J. TI CONSIDERING ADJUSTMENT DISORDERS AS STRESS RESPONSE SYNDROMES FOR DSM-5 SO DEPRESSION AND ANXIETY LA English DT Review ID NATIONAL COMORBIDITY SURVEY; MAJOR DEPRESSION; MODERATION; RELEVANCE; ANXIETY; GENE C1 [Strain, James J.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Friedman, Matthew J.] US Dept Vet Affairs, Natl Ctr PTSD, Washington, DC USA. [Friedman, Matthew J.] Dartmouth Med Sch, Hanover, NH USA. RP Friedman, MJ (reprint author), VA Med Ctr, Natl Ctr PTSD 116D, 215 N Main St, White River Jct, VT 05009 USA. EM matthew.friedman@dartmouth.edu NR 33 TC 27 Z9 27 U1 2 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD SEP PY 2011 VL 28 IS 9 SI SI BP 818 EP 823 DI 10.1002/da.20782 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 823EK UT WOS:000295105100007 PM 21254314 ER PT J AU Gros, DF Frueh, BC Magruder, KM AF Gros, Daniel F. Frueh, B. Christopher Magruder, Kathryn M. TI Prevalence and features of panic disorder and comparison to posttraumatic stress disorder in VA primary care SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Panic disorder; Posttraumatic stress disorder; Veterans; Comorbidity; Health care utilization ID US VETERANS; DSM-IV; PTSD; COMORBIDITY; SYMPTOMS; CLINICS AB Objective: Although panic disorder (PD) is a highly prevalent condition in both community and community primary care settings, little is known about PD in veteran populations, especially in comparison to posttraumatic stress disorder (PTSD). The present study investigated prevalence, comorbidity, physical and mental health impairment, and health care utilization of veterans with PD and PTSD. Method: A total of 884 veterans participated in a cross-sectional investigation in primary care clinics in four Veteran Affairs Medical Centers (VAMCs). Participants completed diagnostic interviews and self-report questionnaires, and a chart review was completed to assess their VAMC health care utilization. Results: A large number of veterans (8.3%) met the diagnostic criteria for PD and reported significantly more severe physical health impairment (pain, general health), mental health impairment (emotional well-being, role limitations) and social functioning than veterans without PD. Veterans with PD also had increased health care utilization for mental health. Further, PD was highly comorbid with PTSD, with similar symptoms across all measures. Conclusions: These findings demonstrate the high prevalence and severe impairment associated with PD in veterans and highlight the need for improved recognition, assessment and specialized treatments for PD in VAMCs and other care settings. Published by Elsevier Inc. C1 [Gros, Daniel F.] Ralph H Johnson VAMC, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Gros, Daniel F.; Magruder, Kathryn M.] Med Univ S Carolina, Charleston, SC 29403 USA. [Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX 77080 USA. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, Charleston, SC 29401 USA. EM grosd@musc.edu RI Schueter, nicos/A-3625-2014 FU Veterans Affairs Health Services Research and Development [VCR-99-010-2]; Ralph H. Johnson VAMC Research Enhancement Award Program [REA08-261] FX This work was partially supported by a grant from Veterans Affairs Health Services Research and Development (VCR-99-010-2). In addition, the authors are members of the Ralph H. Johnson VAMC Research Enhancement Award Program (REA08-261; principal investigator: Leonard Egede, M.D.). 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 US government. There are no conflicts of interest to disclose. NR 25 TC 24 Z9 24 U1 2 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 SEP-OCT PY 2011 VL 33 IS 5 BP 482 EP 488 DI 10.1016/j.genhosppsych.2011.06.005 PG 7 WC Psychiatry SC Psychiatry GA 824MP UT WOS:000295206300012 PM 21816481 ER PT J AU Hutt, E Ruscin, JM Linnebur, SA Fish, DN Oman, KS Fink, RM Radcliff, TA Van Dorsten, B Liebrecht, D Fish, R McNulty, MC AF Hutt, Evelyn Ruscin, J. Mark Linnebur, Sunny A. Fish, Douglas N. Oman, Kathleen S. Fink, Regina M. Radcliff, Tiffany A. Van Dorsten, Brent Liebrecht, Debra Fish, Ron McNulty, Monica C. TI A Multifaceted Intervention to Implement Guidelines Did Not Affect Hospitalization Rates for Nursing Home-Acquired Pneumonia SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Nursing home; pneumonia; hospitalization; guidelines; care processes ID RANDOMIZED CONTROLLED-TRIAL; TERM-CARE FACILITIES; RESIDENTS; MANAGEMENT; PROGRAM; REDUCE; IMPACT AB Objective: Determine whether a comprehensive approach to implementing national consensus guidelines for nursing home acquired pneumonia (NHAP) affected hospitalization rates. Design: Quasi-experimental, mixed-methods, multifaceted, unblinded intervention trial. Setting: Sixteen nursing homes (NHs) from 1 corporation: 8 in metropolitan Denver, CO; 8 in Kansas and Missouri during 3 influenza seasons, October to April 2004 to 2007. Participants: Residents with 2 or more signs and symptoms of systemic lower respiratory tract infection (LRTI); NH staff and physicians were eligible. Intervention: Multifaceted, including academic detailing to clinicians, within-facility nurse change agent, financial incentives, and nursing education. Measurements: Subjects' NH medical records were reviewed for resident characteristics, disease severity, and care processes. Bivariate analysis compared hospitalization rates for subjects with stable and unstable vital signs between intervention and control NHs and time periods. Qualitative interviews were analyzed using content coding. Results: Hospitalization rates for stable residents in both NH groups remained low throughout the study. Few critically ill subjects in the intervention NHs were hospitalized in either the baseline or intervention period. In control NHs, 8.7% of subjects with unstable vital signs were hospitalized during the baseline and 33% in intervention year 2, but the difference was not statistically significant (P = .10). Interviews with nursing staff and leadership confirmed there were significant pressures for, and enablers of, avoiding hospitalization for treatment of acute infections. Conclusions: Secular pressures to avoid hospitalization and the challenges of reaching NH physicians via academic detailing are likely responsible for the lack of intervention effect on hospitalization rates for critically ill NH residents. (J Am Med Dir Assoc 2011; 12: 499-507) C1 [Hutt, Evelyn; Radcliff, Tiffany A.] Univ Colorado Denver, Denver VA Med Ctr, Denver, CO 80220 USA. [Hutt, Evelyn; Ruscin, J. Mark; Linnebur, Sunny A.; Fish, Douglas N.; Oman, Kathleen S.; Fink, Regina M.; Radcliff, Tiffany A.; Van Dorsten, Brent; Liebrecht, Debra; Fish, Ron; McNulty, Monica C.] Univ Colorado Denver, Aurora, CO USA. RP Hutt, E (reprint author), Univ Colorado Denver, Denver VA Med Ctr, 1055 Clermont St,151, Denver, CO 80220 USA. EM evelyn.hutt@ucdenver.edu NR 20 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD SEP PY 2011 VL 12 IS 7 BP 499 EP 507 DI 10.1016/j.jamda.2010.03.011 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 827QJ UT WOS:000295442700005 PM 21450174 ER PT J AU Landau, M Kurella-Tamura, M Shlipak, MG Kanaya, A Strotmeyer, E Koster, A Satterfield, S Simsonick, EM Goodpaster, B Newman, AB Fried, LF AF Landau, Michael Kurella-Tamura, Manjula Shlipak, Michael G. Kanaya, Alka Strotmeyer, Elsa Koster, Annemarie Satterfield, Suzanne Simsonick, Eleanor M. Goodpaster, Bret Newman, Anne B. Fried, Linda F. CA Hlth Aging Body Composition Study TI Correlates of insulin resistance in older individuals with and without kidney disease SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE chronic kidney disease; cystatin C; insulin resistance; subcutaneous fat ID CHRONIC-RENAL-FAILURE; GLOMERULAR-FILTRATION-RATE; METABOLIC SYNDROME; ADIPOSE-TISSUE; PLASMA ADIPONECTIN; MUSCLE COMPOSITION; ABDOMINAL OBESITY; BODY-COMPOSITION; VISCERAL FAT; SENSITIVITY AB Background. Chronic kidney disease (CKD) is associated with insulin resistance (IR). Prior studies have found that in individuals with CKD, leptin is associated with fat mass but resistin is not and the associations with adiponectin are conflicting. This suggests that the mechanism and factors associated with IR in CKD may differ. Methods. Of the 2418 individuals without reported diabetes at baseline, participating in the Health, Aging and Body Composition study, a study in older individuals aged 70-79 years, 15.6% had CKD defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m(2) based on cystatin C. IR was defined as the upper quartile of the homeostasis model assessment. The association of visceral and subcutaneous abdominal fat, percent body fat, muscle fat, lipids, inflammatory markers and adiponectin were tested with logistic regression. Interactions were checked to assess whether the factors associated with IR were different in those with and without CKD. Results. Individuals with IR had a lower eGFR (80.7 +/- 20.9 versus 75.6 +/- 19.6, P < 0.001). After multivariable adjustment, eGFR (odds ratio per 10 mL/min/1.73m(2) 0.92, 95% confidence interval 0.87-0.98) and CKD (1.41, 1.04-1.92) remained independently associated with IR. In individuals with and without CKD, the significant predictors of IR were male sex, black race, higher visceral fat, abdominal subcutaneous fat and triglycerides. In individuals without CKD, IR was associated with lower high-density lipoprotein and current nonsmoking status in multivariate analysis. In contrast, among individuals with CKD, interleukin-6 (IL-6) was independently associated with IR. There was a significant interaction of eGFR with race and IL-6 with a trend for adionectin but no significant interactions with CKD (P > 0.1). In the fully adjusted model, there was a trend for an interaction with adiponectin for eGFR (P = 0.08) and significant for CKD (P = 0.04), where adiponectin was associated with IR in those without CKD but not in those with CKD. Conclusions. In mainly Stage 3 CKD, kidney function is associated with IR; except for adiponectin, the correlates of IR are similar in those with and without CKD. C1 [Strotmeyer, Elsa; Newman, Anne B.; Fried, Linda F.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Landau, Michael] Cleveland Clin, Dept Pathol, Cleveland, OH 44106 USA. [Kurella-Tamura, Manjula] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA. [Shlipak, Michael G.] San Francisco VA, Gen Internal Med Sect, San Francisco, CA USA. [Shlipak, Michael G.; Kanaya, Alka] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Shlipak, Michael G.; Kanaya, Alka] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA USA. [Shlipak, Michael G.; Kanaya, Alka] Univ Calif San Francisco, Dept Biostat, San Francisco, CA USA. [Koster, Annemarie] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Koster, Annemarie] Sch Publ Hlth & Primary Care CAPHRI, Maastricht, Netherlands. [Koster, Annemarie] Maastricht Univ, Dept Internal Med, Maastricht, Netherlands. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Simsonick, Eleanor M.] NIA, NIH, Baltimore, MD 21224 USA. [Goodpaster, Bret; Newman, Anne B.; Fried, Linda F.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. RP Fried, LF (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. EM linda.fried@va.gov RI Koster, Annemarie/E-7438-2010; Newman, Anne/C-6408-2013; Strotmeyer, Elsa/F-3015-2014; Kurella Tamura, Manjula/C-8284-2014 OI Newman, Anne/0000-0002-0106-1150; Kurella Tamura, Manjula/0000-0001-5227-2479; Strotmeyer, Elsa/0000-0002-4093-6036 FU NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIH, National Institute on Aging FX The Health, Aging and Body Composition Study is supported by NIA contract numbers of all participating centers (N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106). This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. The results presented in this paper have not been published previously in whole or part. NR 45 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD SEP PY 2011 VL 26 IS 9 BP 2814 EP 2819 DI 10.1093/ndt/gfq817 PG 6 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 824VZ UT WOS:000295231600016 PM 21248294 ER PT J AU Shang, SB Harton, M Tamayo, MH Shanley, C Palanisamy, GS Caraway, M Chan, ED Basaraba, RJ Orme, IM Ordway, DJ AF Shang, Shaobin Harton, Marisa Tamayo, Marcela Henao Shanley, Crystal Palanisamy, Gopinath S. Caraway, Megan Chan, Edward D. Basaraba, Randall J. Orme, Ian M. Ordway, Diane J. TI Increased Foxp3 expression in guinea pigs infected with W-Beijing strains of M-tuberculosis SO TUBERCULOSIS LA English DT Article DE Mycobacterium tuberculosis; Guinea pig; Foxp3+regulatory T cells; Clinical isolates; W-Beijing strains ID DRUG-RESISTANT TUBERCULOSIS; CELLULAR IMMUNE-RESPONSE; MODEL; PROTECTION; EMERGENCE; VIRULENCE; VACCINES; DISEASE; CELLS AB There is increasing evidence that clinical isolates of Mycobacterium tuberculosis that belong to the W-Beijing genotype of newly emerging strains are often of very high virulence when tested in small animal models, including the mouse and guinea pig. In this report we provide further evidence to support this contention, and show that two W-Beijing strains are of very high virulence when introduced by low dose aerosol into outbred guinea pigs. In addition to severe lung pathology, each of these infections was associated with large influxes of activated CD4 and CD8 T cells into the lungs. Large influxes of macrophages were also observed, but the fraction of these showing evidence of activation by Class-II expression was relatively low. A progressive increase in neutrophils was also seen, with highest levels accumulating in the lungs of the W-Beijing infected animals. In the case of these two infections mRNA levels for TH1 cytokines was elevated early, but these then declined, and were replaced by increasing levels of message encoding for Foxp3, IL-10, and TGF beta. These observations support the hypothesis that W-Beijing strains are potent inducers of regulatory T cells, and that this event may enhance survival and transmission of these bacilli. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Shang, Shaobin; Harton, Marisa; Tamayo, Marcela Henao; Shanley, Crystal; Palanisamy, Gopinath S.; Caraway, Megan; Basaraba, Randall J.; Orme, Ian M.; Ordway, Diane J.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USA. [Chan, Edward D.] Univ Colorado, Sch Med, Denver Vet Affairs Med Ctr, Boulder, CO 80309 USA. [Chan, Edward D.] Univ Colorado, Sch Med, Dept Med, Boulder, CO 80309 USA. [Chan, Edward D.] Univ Colorado, Sch Med, Div Pulm Sci & Crit Care Med, Boulder, CO 80309 USA. RP Ordway, DJ (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USA. EM D.Ordway-Rodriguez@colostate.edu RI Shang, Shaobin/K-5669-2015 OI Shang, Shaobin/0000-0003-4407-1911 FU NIH [AI083856-02, AI070456, 1DP2OD006450]; ARRA funds; College of Veterinary Medicine and Biomedical Sciences, Colorado State University FX This work was supported by NIH grant's AI083856-02, AI070456 and NIH Innovation award 1DP2OD006450, and ARRA funds. Further support was provided by the College of Veterinary Medicine and Biomedical Sciences, Colorado State University. NR 30 TC 28 Z9 28 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PD SEP PY 2011 VL 91 IS 5 SI SI BP 378 EP 385 DI 10.1016/j.tube.2011.06.001 PG 8 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 827XE UT WOS:000295462300005 PM 21737349 ER PT J AU Elderon, L Smolderen, KG Na, B Whooley, MA AF Elderon, Larkin Smolderen, Kim G. Na, Beeya Whooley, Mary A. TI Accuracy and Prognostic Value of American Heart Association-Recommended Depression Screening in Patients With Coronary Heart Disease Data From the Heart and Soul Study SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE cardiovascular diseases; diagnosis; prognosis; psychiatric comorbidity; risk factors ID ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED-CONTROLLED-TRIAL; CASE-FINDING INSTRUMENTS; CARDIOVASCULAR EVENTS; ARTERY-DISEASE; COLLABORATIVE CARE; VALIDITY; EPIDEMIOLOGY; PREVALENCE; PREVENTION AB Background-In 2008, the American Heart Association (AHA) recommended a 2-step screening method, consisting of the 2-item Patient Health Questionnaire (PHQ-2) followed by the 9-item Patient Health Questionnaire (PHQ-9), for identifying depression in cardiovascular patients. The accuracy and prognostic value of this screening method have not been evaluated. Methods and Results-We administered the 2-step AHA-recommended screening algorithm to 1024 patients with stable coronary heart disease and calculated sensitivity and specificity against a gold standard interview for major depressive disorder. Subsequent cardiovascular events (myocardial infarction, stroke, transient ischemic attack, heart failure, or death) were determined during a mean of 6.27 +/- 2.11 years of follow-up. The AHA-recommended screening method had high specificity (0.91; 95% confidence interval, 0.89 to 0.93) but low sensitivity (0.52; 95% confidence interval, 0.4 6 to 0.59) for a diagnosis of major depressive disorder. Participants who screened positive on the AHA depression protocol had a 55% greater risk of events than those who screened negative (age-adjusted hazard ratio, 1.55; 95% confidence interval, 1.21 to 1.97; P=0.0005). After adjustment for age, sex, body mass index, history of myocardial infarction, hypertension, diabetes, heart failure, and high-density lipoprotein levels, screening positive remained associated with a 41% greater rate of cardiovascular events (hazard ratio, 1.41; 95% confidence interval, 1.10 to 1.81; P=0.008). Conclusions-Among outpatients with stable coronary heart disease, the AHA-recommended depression screening protocol is highly specific for depression and identifies patients at risk for adverse cardiovascular outcomes. (Circ Cardiovasc Qual Outcomes. 2011;4:533-540.) C1 [Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Elderon, Larkin] Univ Calif San Francisco, Sch Med, St Lukes Mid Amer Heart & Vasc Inst, Kansas City, MO USA. [Smolderen, Kim G.] Tilburg Univ, Dept Med Psychol & Neuropsychol, Tilburg, Netherlands. [Na, Beeya; Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Whooley, MA (reprint author), Univ Calif San Francisco, Dept Med, 4150 Clement St 111A1, San Francisco, CA 94121 USA. EM mary.whooley@ucsf.edu RI Smolderen, Kim/B-8078-2015 OI Elderon, Larkin/0000-0002-9620-7756 FU UCSF School of Medicine; University of California, San Francisco; Department of Veterans Affairs, the National Heart, Lung, and Blood Institute [R01 HL079235]; American Federation for Aging Research; Robert Wood Johnson Foundation; Ischemia Research and Education Foundation; American Heart Association Pharmaceutical Roundtable; David and Stevie Spina [0875149N] FX Larkin Elderon was supported by the UCSF School of Medicine Dean's Summer Research Fellowship and by a Student Research Training Program grant from the University of California, San Francisco. The Heart and Soul Study was supported by the Department of Veterans Affairs, the National Heart, Lung, and Blood Institute (R01 HL079235); the American Federation for Aging Research; the Robert Wood Johnson Foundation; and the Ischemia Research and Education Foundation. Dr Smolderen was supported by the Outcomes Research post-doctoral fellowship awarded by the American Heart Association Pharmaceutical Roundtable and David and Stevie Spina [grant number AHA No. 0875149N]. The funding organizations had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. NR 33 TC 33 Z9 37 U1 0 U2 5 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 SEP PY 2011 VL 4 IS 5 BP 533 EP 540 DI 10.1161/CIRCOUTCOMES.110.960302 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 822FH UT WOS:000295028800010 PM 21862720 ER PT J AU Leykum, LK Parekh, VI Sharpe, B Boonyasai, RT Centor, RM AF Leykum, Luci K. Parekh, Vikas I. Sharpe, Bradley Boonyasai, Romsai T. Centor, Robert M. TI Tried and True: A Survey of Successfully Promoted Academic Hospitalists SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article DE academic hospital medicine; hospitalists; promotions process ID US MEDICAL-SCHOOLS; INTERNAL-MEDICINE; FACULTY; OPPORTUNITIES; CLINICIAN; EDUCATORS; TENURE; TIME AB BACKGROUND: Academic hospital medicine is a new and rapidly growing field. Hospitalist faculty members often fill roles not typically held by other academic faculty, maintain heavy clinical workloads, and participate in nontraditional activities. Because of these differences, there is concern about how academic hospitalists may fare in the promotions process. OBJECTIVE: To determine factors critical to the promotion of successfully promoted hospitalists who have achieved the rank of either associate professor or professor. DESIGN: A cross-sectional survey. PARTICIPANTS: Thirty-three hospitalist faculty members at 22 academic medical centers promoted to associate professor rank or higher between 1995 and 2008. MEASUREMENTS: Respondents were asked to describe their institution, its promotions process, and the activities contributing to their promotion. We identified trends across respondents. RESULTS: Twenty-six hospitalists responded, representing 20 institutions (79% response rate). Most achieved promotion in a nontenure track (70%); an equal number identified themselves as clinician-administrators and clinician educators (40%). While hospitalists were engaged in a wide range of activities in the traditional domains of service, education, and research, respondents considered peer-reviewed publication to be the most important activity in achieving promotion. Qualitative responses demonstrated little evidence that being a hospitalist was viewed as a hindrance to promotion. CONCLUSIONS: Successful promotion in academic hospital medicine depends on accomplishment in traditional academic domains, raising potential concerns for academic hospitalists with less traditional roles. This study may provide guidance for early-career academic hospitalists and program leaders. Journal of Hospital Medicine 2011;6:411-415. (C) 2011 Society of Hospital Medicine C1 [Leykum, Luci K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hosp Med, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Parekh, Vikas I.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Sharpe, Bradley] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Boonyasai, Romsai T.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD USA. [Centor, Robert M.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. RP Leykum, LK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hosp Med, S Texas Vet Hlth Care Syst, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Leykum@uthscsa.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [01-091, REA 05-129]; American Board of Internal Medicine Foundation FX Dr. Leykum is supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (TRX #01-091 and REA 05-129). 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.; Dr. Boonyasai is supported by an Osler Center for Clinical Excellence faculty scholarship and by the American Board of Internal Medicine Foundation. NR 19 TC 5 Z9 5 U1 0 U2 3 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 SEP PY 2011 VL 6 IS 7 BP 411 EP 415 DI 10.1002/jhm.894 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 824HR UT WOS:000295193500009 PM 21916004 ER PT J AU Axon, RN Cousineau, L Egan, BM AF Axon, R. Neal Cousineau, Laura Egan, Brent M. TI Prevalence and Management of Hypertension in the Inpatient Setting: A Systematic Review SO JOURNAL OF HOSPITAL MEDICINE LA English DT Review DE disease prevention; epidemiology; hypertension ID BLOOD-PRESSURE; HOSPITALIZED-PATIENTS; HEART-DISEASE; PREVENTION; ADULTS; CARE; DISCHARGE; PATTERNS; THERAPY; IMPACT AB BACKGROUND: Hypertension (HTN) is a major cardiovascular risk factor yet control rates remain suboptimal. Thus, improving recognition, treatment, and control of HTN by focusing on novel populations such as hospitalized patients is warranted. Current consensus guidelines do not address inpatient HTN, and little is known about HTN prevalence or patterns of care in this setting. METHODS: We conducted a systematic review of English-language studies published in 1976 or later that reported on HTN prevalence and care patterns among adult inpatients. We included MEDLINE-indexed randomized-controlled trials, meta-analyse:3, and observational studies that: (1) reported estimates of the prevalence of HTN in the inpatient setting, and (2) used HTN diagnosis or treatment as a primary focus. We excluded randomized, controlled trials that recorded measures of inpatient blood pressure but whose focus was not HTN. RESULTS: We identified 9 studies meeting inclusion criteria, and in those studies, HTN was highly prevalent among inpatients, ranging from 50.5% to 72%. Intensification of antihypertensive treatment was inconsistent, and 37% to 77% of hypertensive patients remained hypertensive at the time of discharge. Most patients with inpatient HTN continued to have elevated blood pressures at outpatient follow-up. CONCLUSIONS: Inpatient HTN is prevalent and a large percentage of those with this condition remain hypertensive at the time of discharge and at follow-up. The potential exists for improved recognition and treatment of newly diagnosed and known, but uncontrolled, HTN observed in the inpatient setting. Journal of Hospital Medicine 2011;6:417-422. (C) 2010 Society of Hospital Medicine. C1 [Axon, R. Neal; Egan, Brent M.] Med Univ S Carolina, Dept Internal Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Axon, R. Neal] Ralph H Johnson VAMC, Med Serv, Charleston, SC USA. [Axon, R. Neal] Ralph H Johnson VAMC, Res Serv, Charleston, SC USA. [Cousineau, Laura] MUSC Lib & Educ Ctr, Charleston, SC USA. RP Axon, RN (reprint author), 96 Jonathon Lucas St,POB 250623, Charleston, SC 29425 USA. EM axon@musc.edu NR 30 TC 7 Z9 7 U1 0 U2 3 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 SEP PY 2011 VL 6 IS 7 BP 417 EP 422 DI 10.1002/jhm.804 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 824HR UT WOS:000295193500010 PM 20652961 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Smoking and Outcomes After Knee and Hip Arthroplasty: A Systematic Review SO JOURNAL OF RHEUMATOLOGY LA English DT Review DE SMOKING; ARTHROPLASTY; OUTCOMES; TOTAL KNEE ARTHROPLASTY; TOTAL HIP ARTHROPLASTY ID DEEP-VEIN THROMBOSIS; BODY-MASS INDEX; QUALITY-OF-LIFE; RHEUMATOID-ARTHRITIS; POSTOPERATIVE COMPLICATIONS; RISK-FACTORS; CESSATION INTERVENTION; JOINT REPLACEMENT; CIGARETTE-SMOKING; PREDICTORS AB Objective. Studies have suggested higher rates of perioperative and postoperative complications in smokers compared to nonsmokers. The objective of this systematic review was to assess the association of smoking and postoperative outcomes following total hip arthroplasty (THA) or total knee arthroplasty (TKA). Methods. A search of 6 databases (The Cochrane Library, Scopus, Proquest Dissertation abstracts, CINAHL, Ovid Medline, and Embase) was performed by a Cochrane librarian. All titles and abstracts were screened by 2 independent reviewers with expertise in performing systematic reviews. Studies were included if they were fully published reports that included smoking and any perioperative or postoperative clinical outcome in patients with TKA or THA. Results. A total of 21 studies were included for the review, of which 6 provided multivariable-adjusted analyses, 14 univariate analyses, and one statistical modeling. For most outcomes, results from 1-2 studies could be pooled. Current smokers were significantly more likely to have any postoperative complication (risk ratio 1.24, 95% CI 1.01 to 1.54) and death (risk ratio 1.63, 95% CI 1.06 to 2.51) compared to nonsmokers. Former smokers were significantly more likely to have any post-operative complication (risk ratio 1.32,95% CI 1.05 to 1.66) and death (risk ratio 1.69,95% CI 1.08 to 2.64) compared to nonsmokers. Conclusion. This systematic review found that smoking is associated with significantly higher risk of postoperative complication and mortality following TKA or THA. Studies examining longterm consequences of smoking on implant survival and complications are needed. Smoking cessation may improve outcomes after THA or TKA. (First Release June 1 2011; J Rheumatol 2011;38:1824-34;doi:10.3899/jrheum.101221) C1 [Singh, Jasvinder A.] Univ Alabama, Med Serv, Birmingham Vet Affairs VA Med Ctr, Birmingham, AL 35294 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. [Singh, Jasvinder A.] VA Med Ctr, Med Serv, Minneapolis, MN USA. [Singh, Jasvinder A.] Univ Minnesota, Minneapolis, MN USA. RP Singh, JA (reprint author), Univ Alabama, Med Serv, Birmingham Vet Affairs VA Med Ctr, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU National Institutes of Health (NIH) [1 KL2 RR024151-01] FX Supported by National Institutes of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research). NR 68 TC 33 Z9 34 U1 3 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 SEP PY 2011 VL 38 IS 9 BP 1824 EP 1834 DI 10.3899/jrheum.101221 PG 11 WC Rheumatology SC Rheumatology GA 824FS UT WOS:000295188400004 PM 21632674 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) (vol 19, pg 990, 2011) SO OSTEOARTHRITIS AND CARTILAGE LA English DT Correction C1 [Hunter, D. J.] Univ Sydney, Royal N Shore Hosp, Dept Rheumatol, No Clin Sch, Sydney, NSW 2065, Australia. [Guermazi, A.; Roemer, F. W.] Boston Univ, Sch Med, Dept Radiol, QIC, Boston, MA 02118 USA. [Lo, G. H.] Michael E DeBakey Vet Adm Med Ctr, Houston Hlth Serv Res & Dev HSR&D 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, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Roemer, F. W.] Klinikum Augsburg, Dept Radiol, Augsburg, Germany. RP Hunter, DJ (reprint author), Univ Sydney, Royal N Shore Hosp, Dept Rheumatol, No Clin Sch, Sydney, NSW 2065, Australia. EM David.Hunter@sydney.edu.au RI Hunter, David/A-4622-2010 OI Hunter, David/0000-0003-3197-752X NR 1 TC 2 Z9 2 U1 0 U2 4 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 SEP PY 2011 VL 19 IS 9 BP 1168 EP 1168 DI 10.1016/j.joca.2011.08.001 PG 1 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 825CL UT WOS:000295248400015 ER PT J AU Graber, CJ Shane, AL Weintrub, P Chambers, HF AF Graber, Christopher J. Shane, Andi L. Weintrub, Peggy Chambers, Henry F. TI Clonality of Staphylococcus aureus Colonization over Time in Attendees of a Camp for Children with Chronic Dermatoses SO PEDIATRIC DERMATOLOGY LA English DT Article ID SKIN INFECTIONS AB Chronic dermatoses are risk factors for Staphylococcus aureus colonization; little is known about the significance of transmission between persons with chronic dermatoses (CD) and their contacts. We collected nasal, axillary, and skin swabs for S. aureus from 50 attendees of a camp for children with CD and their families at three time points: start and end of 2005 camp and start of 2006 camp (times A, B, and C, respectively). Thirty-one persons had CD, including epidermolysis bullosa (n = 14), atopic dermatitis (n = 7), ichthyosis (n = 5), and psoriasis (n = 5). Methicillin susceptibility and genotype were determined for all S. aureus isolates. Seventy-one unique S. aureus isolate from 10 clonal complexes (CC) were isolated; 14 (20%) were methicillin-resistant (MRSA). Persons with CD were more likely than those without CD to be colonized with S. aureus at the start of the 2005 (p = 0.01) and 2006 (p = 0.02) camp or at any time or site (p = 0.04) or to be persistently colonized with the same S. aureus CC at the start and end of the 2005 camp. Persons with atopic dermatitis had the highest burden of S. aureus colonization, whereas MRSA was isolated most frequently from attendees with epidermolysis bullosa. Three hospitalizations for skin infections were noted in people with CD between the 2005 and 2006 camps, versus three hospitalizations in the 6 months before the 2005 camp. Although S. aureus colonization was frequent among camp attendees (and in persons with CD in particular), it was diverse and variable. Camp attendance did not appear to affect infection-related clinical outcomes. C1 [Graber, Christopher J.] VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, Los Angeles, CA 90073 USA. [Graber, Christopher J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Graber, Christopher J.; Chambers, Henry F.] San Francisco Gen Hosp, Div Infect Dis, San Francisco, CA 94110 USA. [Graber, Christopher J.; Chambers, Henry F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shane, Andi L.] Emory Univ, Sch Med, Div Pediat Infect Dis, Atlanta, GA USA. [Shane, Andi L.; Weintrub, Peggy] Univ Calif San Francisco, Div Pediat Infect Dis, San Francisco, CA 94143 USA. RP Graber, CJ (reprint author), VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, 11301 Wilshire Blvd,111-F, Los Angeles, CA 90073 USA. EM cgraber@ucla.edu NR 14 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-8046 J9 PEDIATR DERMATOL JI Pediatr. Dermatol. PD SEP-OCT PY 2011 VL 28 IS 5 BP 519 EP 523 DI 10.1111/j.1525-1470.2011.01508.x PG 5 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA 823BI UT WOS:000295096000006 PM 21895757 ER PT J AU Rodriguez, KL Bayliss, NK Alexander, SC Jeffreys, AS Olsen, MK Pollak, KI Garrigues, SK Tulsky, JA Arnold, RM AF Rodriguez, Keri L. Bayliss, Nichole K. Alexander, Stewart C. Jeffreys, Amy S. Olsen, Maren K. Pollak, Kathryn I. Garrigues, Sarah K. Tulsky, James A. Arnold, Robert M. TI Effect of patient and patient-oncologist relationship characteristics on communication about health-related quality of life SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; oncology; patient-provider relationship; communication; quality of life ID PHYSICIAN RELATIONSHIP; DECISION-MAKING; CLINICAL-PRACTICE; CANCER-PATIENT; PREFERENCES; CHEMOTHERAPY; OUTCOMES; SCORES; TRIAL; TRUST AB Objective: To test the effects of patient and patient-oncologist relationship factors on the time spent communicating about health-related quality of life (HRQOL) during outpatient clinic encounters between oncologists and their patients with advanced cancer. Methods: Using mixed methods, we coded for duration of HRQOL talk in a subset of audio-recorded conversations from the Study of Communication in Oncologist-Patient Encounters (SCOPE) Trial. Multivariable linear regression modeling was used to investigate the relationship between duration of HRQOL talk and gender concordance, race concordance, patient education status, patient marital status, and length of the patient-oncologist relationship (i.e. number of previous visits). Results: Sixty-six encounters were analyzed that involved 63 patients and 34 oncologists. Patients were more likely to be female (51%), white (86%), married (78%), and possess a college or more advanced degree (33%). Most oncologists were male (82%) and white (82%). Mean ages were 58.8 years for patients and 44.9 years for oncologists. Regression results showed that the number of a patient's previous visits with their oncologist was significantly associated with a longer duration of HRQOL talk during their audio-recorded clinic visit. The remaining independent variables, gender concordance, race concordance, patient education status, and patient marital status were not significant predictors of duration of HRQOL talk. Conclusions: Our findings suggest that length of the patient-oncologist relationship is related to duration of HRQOL talk. Improvements in HRQOL communication may best be achieved through efforts directed at those in earlier stages of the doctor-patient relationship. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Rodriguez, Keri L.; Bayliss, Nichole K.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Rodriguez, Keri L.; Arnold, Robert M.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Rodriguez, Keri L.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA. [Bayliss, Nichole K.] Univ Pittsburgh, Dept Sociol, Pittsburgh, PA USA. [Alexander, Stewart C.; Jeffreys, Amy S.; Olsen, Maren K.; Tulsky, James A.] Durham VA Med Ctr, Durham, NC USA. [Alexander, Stewart C.; Tulsky, James A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Alexander, Stewart C.; Garrigues, Sarah K.; Tulsky, James A.] Duke Univ, Med Ctr, Ctr Palliat Care, Durham, NC USA. [Olsen, Maren K.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. [Pollak, Kathryn I.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Pollak, Kathryn I.] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Duke Canc Prevent Detect & Control Res Program, Durham, NC 27710 USA. [Tulsky, James A.] Duke Univ, Med Ctr, Ctr Aging & Human Dev, Durham, NC USA. [Arnold, Robert M.] Univ Pittsburgh, Sect Palliat Care & Med Eth, Pittsburgh, PA USA. [Arnold, Robert M.] Univ Pittsburgh, Inst Enhance Palliat Care, Pittsburgh, PA USA. RP Rodriguez, KL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,Bldg 2,Rm 4083E 151C-H, Pittsburgh, PA 15206 USA. EM Keri.rodriguez@va.gov FU VA HSRD [MRP 04-410]; National Cancer Institute [3R01 CA-100387-03S1, R01CA100387]; Department of Veterans Affairs [RCD 07-006] FX Dr Rodriguez is supported by a VA HSR&D Merit Review Entry Program Award (MRP 04-410) and a Minority Supplement Award from the National Cancer Institute (3R01 CA-100387-03S1). Dr Alexander is supported by Health Services Research Career Development Award RCD 07-006 from the Department of Veterans Affairs. This work was supported in part by a grant awarded to Dr Tulsky by the National Cancer Institute (R01CA100387). NR 40 TC 3 Z9 3 U1 2 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD SEP PY 2011 VL 20 IS 9 BP 935 EP 942 DI 10.1002/pon.1829 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 823LB UT WOS:000295122700004 PM 20737643 ER PT J AU Bernardy, NC Hamblen, JL Friedman, MJ Ruzek, JI McFall, ME AF Bernardy, Nancy C. Hamblen, Jessica L. Friedman, Matthew J. Ruzek, Josef I. McFall, Miles E. TI Implementation of a Posttraumatic Stress Disorder Mentoring Program to Improve Treatment Services SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE posttraumatic stress disorder; mentoring; implementation; best management practice AB Three years ago the Department of Veterans Affairs (VA) charged the National Center for PTSD (NCPTSD) to develop a mentoring program to train directors of specialized PTSD clinical programs in effective management skills. There were three reasons for this. First, the number of veterans from the Afghanistan and Iraq conflicts coming to the VA for PTSD treatment was rapidly increasing. Second, a major augmentation in mental health staffing had brought many new clinicians to the VA who were unfamiliar with war-zone-related PTSD and with the VA system of care at a time of changing administrative requirements. Third, the clinical complexity of these veterans required additional mentoring because their PTSD was often associated with depression, mild traumatic brain injury, substance use, chronic pain, aggressive behavior, and/or insomnia. The resulting PTSD Mentoring Program created a national network of program directors to disseminate and implement best management practices by supporting local experts in their mentoring of other VA PTSD program directors. This article describes the implementation of the PTSD Mentoring Program and examines methods of how other programs can successfully use and adapt the mentoring model. A description of what is working and where obstacles still exist for the program is provided. Our experience with the program supports the use of peer mentoring as a method to offer educational training on trauma in different settings and using different modalities. C1 [Bernardy, Nancy C.; Hamblen, Jessica L.; Friedman, Matthew J.] Dartmouth Med Sch, Dept Psychiat, Dartmouth, NS, Canada. [Ruzek, Josef I.] VA Palo Alto Healthcare Syst, Natl Ctr PTSD, Palo Alto, CA USA. [Ruzek, Josef I.] Stanford Univ, Stanford, CA 94305 USA. [McFall, Miles E.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [McFall, Miles E.] Univ Washington, Dept Psychiat, Sch Med, Seattle, WA 98195 USA. [Bernardy, Nancy C.; Hamblen, Jessica L.; Friedman, Matthew J.] White River Junct VAMC, Natl Ctr PTSD, White River Jct, VT USA. [Ruzek, Josef I.] Pacific Grad Sch Psychol, Palo Alto, CA USA. RP Bernardy, NC (reprint author), White River Junct VA Med Ctr, Natl Ctr PTSD 116D, 215 N Main St, White River Jct, VT 05001 USA. EM nancy.bernardy@va.gov NR 9 TC 6 Z9 6 U1 1 U2 2 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD SEP PY 2011 VL 3 IS 3 SI SI BP 292 EP 299 DI 10.1037/a0024847 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 823GF UT WOS:000295109800012 ER PT J AU Krum, H Elsik, M Schneider, HG Ptaszynska, A Black, M Carson, PE Komajda, M Massie, BM McKelvie, RS McMurray, JJ Zile, MR Anand, IS AF Krum, Henry Elsik, Maros Schneider, Hans G. Ptaszynska, Agata Black, Marion Carson, Peter E. Komajda, Michel Massie, Barry M. McKelvie, Robert S. McMurray, John J. Zile, Michael R. Anand, Inder S. TI Relation of Peripheral Collagen Markers to Death and Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction Results of the I-PRESERVE Collagen Substudy SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; diastolic pressure; ventricular ejection fraction; collagen; fibrosis; osteopontin ID MYOCARDIAL FIBROSIS; DIASTOLIC DYSFUNCTION; TERMINAL PROPEPTIDE; SYSTOLIC FUNCTION; TURNOVER; DISEASE; CARDIOMYOPATHY; PROCOLLAGEN; IRBESARTAN; INSIGHTS AB Background-Heart failure with preserved ejection fraction (HFPEF) is a common and increasing public health problem. Myocardial fibrosis is a key pathological feature of HFPEF. Peripheral collagen markers may reflect this excess fibrosis; however, the relation of these markers to prognosis in patients with HFPEF has not as yet been determined. Methods and Results-This substudy of the Irbesartan in Heart Failure With Preserved Systolic Function (I-PRESERVE) trial measured plasma levels of procollagen type I amino-terminal peptide, procollagen type III amino-terminal peptide, and osteopontin in 334 patients with HFPEF. Measurements were performed at baseline and 6 months after randomization to placebo or irbesartan 300 mg/day. The relation of baseline collagen markers to the I-PRESERVE primary end point (all-cause death and hospitalization for prespecified cardiovascular causes) was evaluated by single and multivariable analysis. Similar evaluations were performed for all-cause death alone as well as heart failure events (death or hospitalization because of heart failure). Increased plasma levels of collagen markers at baseline were associated with increased frequency of the study primary end point for all collagen markers. For each 10-mu g/L increase in procollagen type I amino-terminal peptide, the hazard ratio (HR) for the primary end point was 1.09 (95% CI, 1.052 to 1.13; P<0.0001); for each 10-mu g/L increase in procollagen type III amino-terminal peptide procollagen type I amino-terminal peptide, the HR was 2.47 (95% CI, 0.97 to 6.33; P=0.059); and for each 10-nmol/L increase in osteopontin, the HR was 1.084 (95% CI, 1.026 to 1.15; P=0.004). No variable remained significant as an independent predictor when introduced into a multivariable model. Both treatment groups tended to reduce collagen markers, with the reduction significantly greater for placebo versus irbesartan for procollagen type III amino-terminal peptide only (P=0.0185). Conclusions-Increased peripheral collagen turnover markers were not independently associated with increased mortality and cardiovascular hospitalization in an HFPEF population on multivariable analysis but were associated on single-variable analysis. These findings provide some support to the hypothesis that pathological fibrosis in the heart, and possibly the peripheral vasculature, may be contributory to adverse clinical outcomes in patients with HFPEF. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238.(Circ Heart Fail. 2011;4:561-568.) C1 [Krum, Henry; Elsik, Maros] Monash Univ, Alfred Hosp, Ctr Cardiovasc Res & Educ Therapeut, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Schneider, Hans G.; Black, Marion] Alfred Hosp, Dept Pathol, Melbourne, Vic, Australia. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. [Ptaszynska, Agata] Bristol Myers Squibb Co, Princeton, NJ USA. [Komajda, Michel] Univ Paris 06, Paris, France. [Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [McKelvie, Robert S.] McMaster Univ, Hamilton, ON, Canada. [McMurray, John J.] Univ Glasgow, Glasgow, Lanark, Scotland. [Zile, Michael R.] VA Med Ctr, RHJ Dept, Charleston, SC USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Anand, Inder S.] VA Med Ctr, Minneapolis, MN USA. [Anand, Inder S.] Univ Minnesota, Minneapolis, MN USA. RP Krum, H (reprint author), Monash Univ, Alfred Hosp, Ctr Cardiovasc Res & Educ Therapeut, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. EM henry.krum@monash.edu OI mcmurray, john/0000-0002-6317-3975 FU Bristol-Myers Squibb; Sanofi-Aventis; Janssen-Cilag; Abbott; Roche; Veterans Administration (VA) nonprofit foundation; Glasgow University FX This study was supported by Bristol-Myers Squibb and Sanofi-Aventis.; Dr Krum has received honoraria for being the I-PRESERVE Australia coordinator. Dr Schneider has received research grant support for NGAL in congestive heart failure, fatty acid-binding protein in brain injury, and high-sensitivity troponin in general medicine; received other research support from Janssen-Cilag for brain natriuretic peptide study; received expense payment only from Abbott and Roche; has served as an expert witness for troponin in diagnosis of acute myocardial infarction (legal case); and has served as an expert witness for Victorian Ombudsman. Dr Ptaszynska is an employee of Bristol-Myers Squibb, who sponsored data collection. Dr Michel Komajda has served on the speakers bureau for Servier, Menarini, Bristol-Meyers Squibb, AstraZeneca, GlaxoSmithKline, and Sanofi-Aventis and has received honoraria from Servier, Duke University, Nile Therapeutics, and Sanofi-Aventis. Dr Massie has received research grant support from a Veterans Administration (VA) nonprofit foundation and received payments to cover the costs for patients enrolled at the site, has received other research support from a VA research grant related to implantable cardioverter-defibrillator in the VA system, and has received consultant fees from Bristol-Meyers Squibb for time spent as principal investigator of the trial. Dr McKelvie has received honoraria from Bristol-Meyers Squibb. Dr McMurray has received research support from Glasgow University for participation as co-principal investigator in a clinical trial program that included a study in HFPEF. Dr Zile serves as a member of the Executive Committee and chairman of the EndPoints Committee. Dr Anand has received research grant support as principal investigator on I-Preserve and honoraria as a member of the EndPoint Committee. Drs Krum, Carson, Komajda, Massie, McKelvie, McMurrray, Zile, and Anand are members of the I-PRESERVE Steering Committee and have received honoraria and travel support from Bristol-Myers Squibb to attend Steering Committee meetings. NR 19 TC 35 Z9 37 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 SEP PY 2011 VL 4 IS 5 BP 561 EP 568 DI 10.1161/CIRCHEARTFAILURE.110.960716 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 822HQ UT WOS:000295035000008 PM 21750125 ER PT J AU Anand, IS Rector, TS Cleland, JG Kuskowski, M McKelvie, RS Persson, H McMurray, JJ Zile, MR Komajda, M Massie, BM Carson, PE AF Anand, Inder S. Rector, Thomas S. Cleland, John G. Kuskowski, Michael McKelvie, Robert S. Persson, Hans McMurray, John J. Zile, Michael R. Komajda, Michel Massie, Barry M. Carson, Peter E. TI Prognostic Value of Baseline Plasma Amino-Terminal Pro-Brain Natriuretic Peptide and Its Interactions With Irbesartan Treatment Effects in Patients With Heart Failure and Preserved Ejection Fraction Findings From the I-PRESERVE Trial SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure, diastolic; ventricular ejection fraction; pro-brain natriuretic peptide (1-76); pathophysiology; prognosis; biological markers ID DIASTOLIC DYSFUNCTION; PREDICTION; CARVEDILOL; MORTALITY; ALISKIREN; OUTCOMES; CORONA; HEFT AB Background-Plasma concentrations of natriuretic peptides (NPs) are associated with morbidity and mortality in patients with systolic heart failure (HF). However, the role of NP as a prognostic marker in patients with HF and preserved ejection fraction (HFpEF) has not been studied in a large cohort of well-characterized patients. Moreover, it is unclear whether treatments have a differential effect on morbidity and mortality across the spectrum of NP levels. Methods and Results-N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured at baseline in 3480 patients in the I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction Trial). In a multivariable Cox regression model, NT-proBNP above the median of 339 pg/mL was independently associated with an increased risk of the primary end point of all-cause mortality and prespecified cardiovascular hospitalizations (adjusted hazard ratio [HR], 1.79; 95% CI, 1.56 to 2.10; P<0.001); all-cause mortality (adjusted HR, 2.04; 95% CI, 1.68 to 2.47; P<0.001); and a composite of HF events, including death due to worsening HF or sudden death or hospitalization due to worsening HF (adjusted HR, 1.77; 95% CI, 1.43 to 2.20; P<0.001). There were significant interactions between the effect of irbesartan and median split of baseline NT-proBNP for the primary outcome (P=0.005), all-cause mortality (P=0.05), and the HF composite outcome (P<0.001). Use of irbesartan was associated with improved outcomes in patients with NT-proBNP below, but not above, the median. After adjusting for 20 baseline covariates, irbesartan still had a beneficial effect on the primary outcome (HR, 0.74; 95% CI, 0.60 to 90; P=0.003), all-cause mortality (HR, 0.75; 95% CI, 0.56 to 0.99; P=0.046), and HF composite outcome (HR, 0.57; 95% CI, 0.41 to 0.80; P=0.001) in patients with NT-proBNP below the median. Conclusions-The unexpected benefit of irbesartan in lower-risk patients with HFpEF in this post hoc analysis may indicate effects on early, but not later, high-risk stages of the disease. These findings question the strategy of using elevated plasma concentrations of NP as a patient selection criterion in HFpEF trials. More studies are needed to support or contest this practice. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238. (Circ Heart Fail. 2011;4:569-577.) C1 [Anand, Inder S.; Rector, Thomas S.; Kuskowski, Michael] VA Med Ctr, Minneapolis, MN 55417 USA. [Anand, Inder S.; Rector, Thomas S.; Kuskowski, Michael] Univ Minnesota, Minneapolis, MN USA. [Cleland, John G.] Univ Hull, Castle Hill Hosp, Dept Cardiol, Kingston Upon Hull, Yorks, England. [McKelvie, Robert S.] Populat Hlth Res Inst, Hamilton, ON, Canada. [McKelvie, Robert S.] McMaster Univ, Hamilton, ON, Canada. [Persson, Hans] Danderyd Hosp, Dept Clin Sci, Karolinska Inst, Stockholm, Sweden. [McMurray, John J.] British Heart Fdn Glasgow, Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Zile, Michael R.] Vet Affairs Med Ctr, RHJ Dept, Charleston, SC 29403 USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Komajda, Michel] Univ Paris 06, Pitie Salpetriere Hosp, Paris, France. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Carson, Peter E.] Washington Vet Affairs Med Ctr, Washington, DC USA. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. RP Anand, IS (reprint author), VA Med Ctr, Cardiol 111-C,1 Vet Dr, Minneapolis, MN 55417 USA. EM anand001@umn.edu OI Cleland, John/0000-0002-1471-7016; mcmurray, john/0000-0002-6317-3975 FU Veterans Health Administration Health Services [HFP-98-001]; Center for Epidemiology and Clinical Research at the Minneapolis VA Medical Center FX Dr Rector was supported by Veterans Health Administration Health Services Research & Development Grant HFP-98-001and the Center for Epidemiology and Clinical Research at the Minneapolis VA Medical Center. The views expressed herein do not necessarily represent the views of the Department of Veterans Affairs. NR 25 TC 64 Z9 65 U1 0 U2 5 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 SEP PY 2011 VL 4 IS 5 BP 569 EP 577 DI 10.1161/CIRCHEARTFAILURE.111.962654 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 822HQ UT WOS:000295035000009 PM 21715583 ER PT J AU Wrobel, JS Reiber, GE AF Wrobel, James S. Reiber, Gayle E. TI Time for a Victory Lap or Time to Raise the Levees: A Perspective on Complication Reduction and New-Onset Diabetes SO DIABETES CARE LA English DT Editorial Material ID 10-YEAR FOLLOW-UP; PREVENTION PROGRAM; OUTCOMES; TRENDS; INTERVENTIONS; AMPUTATION; THERAPY C1 [Wrobel, James S.] Univ Michigan, Sch Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA. [Reiber, Gayle E.] VA Puget Sound, Hlth Serv Res & Dev, Rehabil Res & Dev, Seattle, WA USA. [Reiber, Gayle E.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Reiber, Gayle E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Wrobel, JS (reprint author), Univ Michigan, Sch Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA. EM jswrobel@med.umich.edu NR 21 TC 0 Z9 0 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 SEP PY 2011 VL 34 IS 9 BP 2130 EP 2132 DI 10.2337/dc11-1069 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 824IH UT WOS:000295195100042 PM 21868782 ER PT J AU DeHaven, BC Gupta, K Isaacs, SN AF DeHaven, Brian C. Gupta, Kushol Isaacs, Stuart N. TI The vaccinia virus A56 protein: a multifunctional transmembrane glycoprotein that anchors two secreted viral proteins SO JOURNAL OF GENERAL VIROLOGY LA English DT Review ID COMPLEMENT-CONTROL PROTEIN; INTRACELLULAR MATURE VIRUS; ENTRY-FUSION COMPLEX; CELL-CELL-FUSION; INFECTED-CELLS; NUCLEOTIDE-SEQUENCE; HEMAGGLUTININ GENE; ECTROMELIA VIRUS; HUMAN MONKEYPOX; BALB/C MICE AB The vaccinia virus A56 protein was one of the earliest-described poxvirus proteins with an identifiable activity. While originally characterized as a haemagglutinin protein, A56 has other functions as well. The A56 protein is capable of binding two viral proteins, a serine protease inhibitor (K2) and the vaccinia virus complement control protein (VCP), and anchoring them to the surface of infected cells. This is important; while both proteins have biologically relevant functions at the cell surface, neither one can locate there on its own. The A56-K2 complex reduces the amount of virus superinfecting an infected cell and also prevents the formation of syncytia by infected cells; the A56-VCP complex can protect infected cells from complement attack. Deletion of the A56R gene results in varying effects on vaccinia virus virulence. In addition, since the gene encoding the A56 protein is non-essential, it can be used as an insertion point for foreign genes and has been deleted in some viruses that are in clinical development as oncolytic agents. C1 [DeHaven, Brian C.; Isaacs, Stuart N.] Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Gupta, Kushol] Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. [Gupta, Kushol] Univ Penn, Sch Med, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. [Isaacs, Stuart N.] Philadelphia Vet Affairs Med Ctr, Infect Dis Sect, Philadelphia, PA 19104 USA. RP Isaacs, SN (reprint author), Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. EM isaacs@mail.med.upenn.edu FU Public Health Service, National Institute of Allergy and Infectious Disease [U01-AI077913, U01-AI066333, U54-AI057168]; [T32 AI07324] FX The authors would like to thank Joe Esposito for helpful discussions and the reviewers of the submitted manuscript whose comments helped improve this mini-review. S. N. I. is supported in part by Public Health Service grants U01-AI077913, U01-AI066333 and U54-AI057168 (Middle Atlantic Regional Center of Excellence in Biodefense and Emerging Infectious Diseases) from the National Institute of Allergy and Infectious Disease. B. C. D. is supported by institutional training grants T32 AI07324 and U01-AI066333. NR 86 TC 1 Z9 5 U1 0 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 EI 1465-2099 J9 J GEN VIROL JI J. Gen. Virol. PD SEP PY 2011 VL 92 BP 1971 EP 1980 DI 10.1099/vir.0.030460-0 PN 9 PG 10 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 822BO UT WOS:000295018900001 PM 21715594 ER PT J AU Hoen, PW de Jonge, P Na, BY Farzaneh-Far, R Epel, E Lin, J Blackburn, E Whooley, MA AF Hoen, Petra W. de Jonge, Peter Na, Bee Ya Farzaneh-Far, Ramin Epel, Elissa Lin, Jue Blackburn, Elizabeth Whooley, Mary A. TI Depression and Leukocyte Telomere Length in Patients With Coronary Heart Disease: Data From The Heart and Soul Study SO PSYCHOSOMATIC MEDICINE LA English DT Article DE depression; telomere length; stable CHD ID CARDIOVASCULAR EVENTS; LONGITUDINAL FINDINGS; PHYSICAL-ACTIVITY; ARTERY-DISEASE; STRESS; VALIDITY; HEALTH; METAANALYSIS; ACTIVATION; MORTALITY AB Objective: Shortened telomere length has been associated with mortality in patients with coronary heart disease (CHD) and is considered as an emerging marker of biologic age. Whether depression is associated with telomere length or trajectory has not been evaluated in patients with CHD. Methods: In a prospective cohort study, we measured leukocyte telomere length in 952 participants with stable CHD at baseline and in 608 of these participants after 5 years of follow-up. The presence of major depressive disorder in the past month was assessed using the computerized diagnostic interview schedule at baseline. We used linear and logistic regression models to evaluate the association of depression with baseline and 5-year change in leukocyte telomere length. Results: Of the 952 participants, 206 (22%) had major depression at baseline. After the adjustment for age and sex, the patients with current major depressive disorder had shorter baseline telomere length than those without depression (mean [standard error] = 0.86 [0.02] versus 0.90 [0.01]; p = .02). This association was similar (but no longer statistically significant) after adjustment for body mass index, smoking, diabetes, left ventricular ejection fraction, statin use, antidepressant use, physical inactivity, and anxiety (0.85 [0.02] versus 0.89 [0.01], p = .06). Depression was not predictive of 5-year change in telomere length after adjustment for the mentioned covariates and baseline telomere length. Conclusions: Depression is associated with reduced leukocyte telomere length in patients with CHD but does not predict 5-year change in telomere length. Future research is necessary to elucidate the potential mechanisms underlying the association between depression and telomere length. C1 [Hoen, Petra W.; de Jonge, Peter] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 GZ Groningen, Netherlands. [de Jonge, Peter] Tilburg Univ, Dept Med Psychol, NL-5000 LE Tilburg, Netherlands. [Na, Bee Ya; Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Farzaneh-Far, Ramin; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Farzaneh-Far, Ramin] San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. [Epel, Elissa] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Lin, Jue; Blackburn, Elizabeth] Univ San Francisco, Dept Biochem & Biophys, San Francisco, CA 94117 USA. RP Hoen, PW (reprint author), Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychiat Epidemiol, CC72,Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM p.w.hoen@med.umcg.nl RI de Jonge, peter/L-6395-2013 OI de Jonge, peter/0000-0002-0866-6929 FU Dutch Medical Research Council [016.086.397]; Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development service; National Heart Lung and Blood Institute [R01 HL079235]; American Federation for Aging Research; Robert Wood Johnson Foundation; Ischemia Research and Education Foundation; Nancy Kirwan Heart Research Fund; American Heart Association [0875014N] FX P.d.J. was supported by a VIDI Grant from the Dutch Medical Research Council (Grant 016.086.397). The Heart and Soul Study was supported by the Department of Veterans Affairs Epidemiology Merit Review Program, the Department of Veterans Affairs Health Services Research and Development service, the National Heart Lung and Blood Institute (R01 HL079235), the American Federation for Aging Research (Paul Beeson Scholars Program), the Robert Wood Johnson Foundation (Generalist Physician Faculty Scholars Program), the Ischemia Research and Education Foundation, and the Nancy Kirwan Heart Research Fund. R.F.-F. is supported by the American Heart Association Fellow-to-Faculty Transition Award #0875014N. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 38 TC 54 Z9 56 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP PY 2011 VL 73 IS 7 BP 541 EP 547 DI 10.1097/PSY.0b013e31821b1f6e PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 823KX UT WOS:000295122300004 PM 21597035 ER PT J AU Puterman, E O'Donovan, A Adler, NE Tomiyama, AJ Kemeny, M Wolkowitz, OM Epel, E AF Puterman, Eli O'Donovan, Aoife Adler, Nancy E. Tomiyama, A. Janet Kemeny, Margaret Wolkowitz, Owen M. Epel, Elissa TI Physical Activity Moderates Effects of Stressor-Induced Rumination on Cortisol Reactivity SO PSYCHOSOMATIC MEDICINE LA English DT Article DE acute stress; rumination; physical activity; mixed modeling; cortisol reactivity ID ALL-CAUSE MORTALITY; CARDIOVASCULAR-DISEASE; ALZHEIMERS-DISEASE; CARDIORESPIRATORY FITNESS; PERSEVERATIVE COGNITION; SYNAPTIC-PLASTICITY; PSYCHOSOCIAL STRESS; EXERCISE TREATMENT; MAJOR DEPRESSION; CONTROLLED-TRIAL AB Objective: Physically active individuals have lower rates of morbidity and mortality, and recent evidence indicates that physical activity may be particularly beneficial to those experiencing chronic stress. The tendency to ruminate increases and prolongs physiological stress responses, including hypothalamic-pituitary-adrenal (HPA) axis responses as indexed by cortisol reactivity to stressful experiences. We examined the association between ruminating in response to a laboratory stressor task and HPA axis reactivity and recovery and examined whether a physically active life-style moderates the associations between rumination and cortisol output trajectories. Methods: Forty-six postmenopausal women underwent the Trier Social Stress Test, whereas salivary cortisol was repeatedly measured. Twenty-five minutes after the end of the stressor, participants reported level of rumination in response to the stress. Results: Findings indicate that physical activity moderated the initial rate (B = -0.10, standard error = 0.04, p < .05) and curvature (B = -0.03, standard error = 0.01, p = .06) of the relationship between rumination and log-transformed cortisol trajectory. Among sedentary participants, those who responded to the stressor with higher levels of rumination had a more rapid initial increase in cortisol level (0.26 versus 0.21, p < .001), a later peak in cortisol reactivity (56 versus 39 minutes), and a delayed recovery from stress (curvature: -0.07 versus -0.08, p < .001) compared with those with lower levels of rumination. In active participants, cortisol trajectories were equivalent, regardless of the level of rumination. Conclusions: In sum, individuals who maintain a physically active life-style may be protected against the effects of rumination on HPA axis reactivity to and recovery from acute stress. C1 [Puterman, Eli; O'Donovan, Aoife; Adler, Nancy E.; Kemeny, Margaret; Wolkowitz, Owen M.; Epel, Elissa] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94118 USA. [O'Donovan, Aoife] San Francisco VA Med Ctr, San Francisco, CA USA. [Tomiyama, A. Janet] Rutgers State Univ, Dept Psychol, New Brunswick, NJ 08903 USA. [Tomiyama, A. Janet] Rutgers State Univ, Dept Nutr, New Brunswick, NJ 08903 USA. RP Puterman, E (reprint author), Univ Calif San Francisco, Dept Psychiat, 3333 Calif St,Suite 465, San Francisco, CA 94118 USA. EM eli.puterman@ucsf.edu OI Puterman, Eli/0000-0002-5898-2348 FU Division of Behavioral and Social Research at the National Institute on Aging/National Institutes of Health FX The research study was supported by the Division of Behavioral and Social Research at the National Institute on Aging/National Institutes of Health R56 Grant (E.E.). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 84 TC 19 Z9 19 U1 2 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP PY 2011 VL 73 IS 7 BP 604 EP 611 DI 10.1097/PSY.0b013e318229e1e0 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 823KX UT WOS:000295122300012 PM 21873586 ER PT J AU Liu, DP Zhou, XH AF Liu, Danping Zhou, Xiao-Hua TI Semiparametric Estimation of the Covariate-Specific ROC Curve in Presence of Ignorable Verification Bias SO BIOMETRICS LA English DT Article DE Alzheimer's disease; Covariate-specific ROC curve; Ignorable missingness; Verification bias; Weighted estimating equations ID ASSESSING ACCURACY; DIAGNOSTIC-TESTS; DISEASE; LIKELIHOOD; DEMENTIA; AREA AB Covariate-specific receiver operating characteristic (ROC) curves are often used to evaluate the classification accuracy of a medical diagnostic test or a biomarker, when the accuracy of the test is associated with certain covariates. In many large-scale screening tests, the gold standard is subject to missingness due to high cost or harmfulness to the patient. In this article, we propose a semiparametric estimation of the covariate-specific ROC curves with a partial missing gold standard. A location-scale model is constructed for the test result to model the covariates' effect, but the residual distributions are left unspecified. Thus the baseline and link functions of the ROC curve both have flexible shapes. With the gold standard missing at random (MAR) assumption, we consider weighted estimating equations for the location-scale parameters, and weighted kernel estimating equations for the residual distributions. Three ROC curve estimators are proposed and compared, namely, imputation-based, inverse probability weighted, and doubly robust estimators. We derive the asymptotic normality of the estimated ROC curve, as well as the analytical form of the standard error estimator. The proposed method is motivated and applied to the data in an Alzheimer's disease research. C1 [Liu, Danping; Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, NW HSR&D Ctr Excellence, Seattle, WA 98108 USA. RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA. EM dpliu@u.washington.edu; azhou@u.washington.edu RI Liu, Danping/D-2544-2013 FU NIH/NIA [U01AG016976, NSFC30728019] FX The work was supported in part by NIH/NIA grant U01AG016976 and NSFC30728019. This article does not necessarily represent the findings and conclusions of VA HSR&D. Dr X-HZ is presently a Core Investigator and Biostatistics Unit Director at HSR&D Center of Excellence, Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington. NR 21 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2011 VL 67 IS 3 BP 906 EP 916 DI 10.1111/j.1541-0420.2011.01562.x PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 819XE UT WOS:000294866800024 PM 21361890 ER PT J AU Holschneider, DP Guo, YM Roch, M Norman, KM Scremin, OU AF Holschneider, Daniel P. Guo, Yumei Roch, Margareth Norman, Keith M. Scremin, Oscar U. TI Acetylcholinesterase Inhibition and Locomotor Function after Motor-Sensory Cortex Impact Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE acetylcholinesterase; cholinergic; motor function; neurorehabilitation; TBI ID TRAUMATIC BRAIN-INJURY; ORAL PHYSOSTIGMINE; MEMORY DEFICITS; WORKING MEMORY; HEAD-INJURY; LONG-TERM; RECOVERY; RATS; RIVASTIGMINE; DONEPEZIL AB Traumatic brain injury (TBI) induces transient or persistent dysfunction of gait and balance. Enhancement of cholinergic transmission has been reported to accelerate recovery of cognitive function after TBI, but the effects of this intervention on locomotor activity remain largely unexplored. The hypothesis that enhancement of cholinergic function by inhibition of acetylcholinesterase (AChE) improves locomotion following TBI was tested in Sprague-Dawley male rats after a unilateral controlled cortical impact (CCI) injury of the motor-sensory cortex. Locomotion was tested by time to fall on the constant speed and accelerating Rotarod, placement errors and time to cross while walking through a horizontal ladder, activity monitoring in the home cages, and rearing behavior. Assessments were performed the 1st and 2nd day and the 1st, 2nd, and 3rd week after TBI. The AChE inhibitor physostigmine hemisulfate (PHY) was administered continuously via osmotic minipumps implanted subcutaneously at the rates of 1.6-12.8 mu mol/kg/day. All measures of locomotion were impaired by TBI and recovered to initial levels between 1 and 3 weeks post-TBI, with the exception of the maximum speed achievable on the accelerating Rotarod, as well as rearing in the open field. PHY improved performance in the accelerating Rotarod at 1.6 and 3.2 mu mol/kg/day (AChE activity 95 and 78% of control, respectively), however, higher doses induced progressive deterioration. No effect or worsening of outcomes was observed at all PHY doses for home cage activity, rearing, and horizontal ladder walking. Potential benefits of cholinesterase inhibition on locomotor function have to be weighed against the evidence of the narrow range of useful doses. C1 [Holschneider, Daniel P.; Guo, Yumei] Univ So Calif, USC Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Holschneider, Daniel P.] Univ So Calif, USC Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. [Holschneider, Daniel P.] Univ So Calif, USC Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90033 USA. [Holschneider, Daniel P.; Roch, Margareth; Norman, Keith M.; Scremin, Oscar U.] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Scremin, Oscar U.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. RP Holschneider, DP (reprint author), Univ So Calif, USC Keck Sch Med, Dept Psychiat & Behav Sci, 1333 San Pablo St,BMT 403,MC9112, Los Angeles, CA 90033 USA. EM holschne@usc.edu FU Department of Veterans Affairs Rehabilitation Research & Development Merit Review (VA RRD) [B5089R] FX This work was supported by a Department of Veterans Affairs Rehabilitation Research & Development Merit Review (VA RR&D) #B5089R and a VA RR&D Research Career Scientist award (O.U.S). NR 42 TC 12 Z9 12 U1 2 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD SEP PY 2011 VL 28 IS 9 BP 1909 EP 1919 DI 10.1089/neu.2011.1978 PG 11 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 821AK UT WOS:000294947000020 PM 21787180 ER PT J AU Saha, S Beach, MC AF Saha, Somnath Beach, Mary Catherine TI The impact of patient-centered communication on patients' decision making and evaluations of physicians: A randomized study using video vignettes SO PATIENT EDUCATION AND COUNSELING LA English DT Article; Proceedings Paper CT Conference of the European-Association-for-Communication-in-Healthcare (EACH) CY 2010 CL Verona, ITALY SP European Assoc Commun Hlth Care DE Physician-patient relations; Patient-centered care; Communication; Decision making ID PRIMARY-CARE; OUTCOMES; HEALTH; CONSULTATIONS; RELIABILITY; MEDICINE; SCALE; TRUST; MODEL AB Objective: To assess the impact of patient-centered communication (PCC) behaviors on patients' evaluations of physicians and acceptance of clinical recommendations. Methods: We randomized 248 patients to view video-recorded, standardized vignettes, depicting a cardiologist using a high vs. low degree of PCC while recommending bypass surgery to a patient with angina and 3-vessel coronary artery disease. We compared patients' ratings of the physician and their decision making in response to the physician's recommendation, for high vs. low PCC vignettes. Results: Patients viewing high PCC vignettes rated the video physician more favorably overall (3.01 vs. 2.12, p < 0.001) and as more competent (3.22 vs. 2.66, p < 0.001) and trustworthy (2.93 vs. 2.28, p < 0.001) than those viewing the low PCC version (0-4 range for all scales). Patients viewing the high PCC version more frequently said they would undergo bypass surgery (96% vs. 74%, p < 0.001) if they were the patient in the video. Conclusion: Patients expressed greater confidence in physicians who used more PCC behaviors, and greater willingness to accept an evidence-based recommendation. Practice implications: PCC may make physicians more effective in the delivery of evidence-based care. Published by Elsevier Ireland Ltd. C1 [Saha, Somnath] Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR 97239 USA. [Saha, Somnath] Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA. [Beach, Mary Catherine] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. RP Saha, S (reprint author), Portland VA Med Ctr, Gen Internal Med Sect, 3710 SW US Vet Hosp Rd P2HSRD, Portland, OR 97239 USA. EM sahas@ohsu.edu FU NIMH NIH HHS [R34 MH089279-01A1, R34 MH089279-02, R34 MH089279]; NIMHD NIH HHS [L60 MD000303, L60 MD000303-01, L60 MD000303-02] NR 33 TC 26 Z9 27 U1 1 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD SEP PY 2011 VL 84 IS 3 SI SI BP 386 EP 392 DI 10.1016/j.pec.2011.04.023 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 820XM UT WOS:000294939400015 PM 21600723 ER PT J AU Mehta, NK Chang, VW AF Mehta, Neil K. Chang, Virginia W. TI Secular Declines in the Association Between Obesity and Mortality in the United States SO POPULATION AND DEVELOPMENT REVIEW LA English DT Article ID BODY-MASS-INDEX; US ADULTS; LIFE EXPECTANCY; RISK-FACTORS; DEATHS; OVERWEIGHT; TRENDS; UNDERWEIGHT; PREVALENCE; SMOKING AB Recent research suggests that rising obesity will restrain future gains in US life expectancy and that obesity is an important contributor to the current shortfall in US longevity compared to other high-income countries. Estimates of the contribution of obesity to current and future national-level mortality patterns are sensitive to estimates of the magnitude of the association between obesity and mortality at the individual level. We assessed secular trends in the obesity/mortality association among cohorts of middle-aged adults between 1948 and 2006 using three long-running US data sources: the Framingham Heart Study, the National Health and Nutrition Examination Survey, and the National Health Interview Survey. We find substantial declines over time in the magnitude of the association between obesity and overall mortality and, in certain instances, cardiovascular-specific mortality. We conclude that estimates of the contribution of obesity to current national-level mortality patterns should take into account recent reductions in the magnitude of the obesity and mortality association. C1 [Mehta, Neil K.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Chang, Virginia W.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Chang, Virginia W.] Univ Penn, Philadelphia, PA 19104 USA. RP Mehta, NK (reprint author), Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. FU NIA NIH HHS [T32 AG000177, T32 AG000177-19] NR 46 TC 31 Z9 31 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0098-7921 J9 POPUL DEV REV JI Popul. Dev. Rev. PD SEP PY 2011 VL 37 IS 3 BP 435 EP + DI 10.1111/j.1728-4457.2011.00429.x PG 18 WC Demography; Sociology SC Demography; Sociology GA 818PB UT WOS:000294764500002 PM 22110257 ER PT J AU Handel, DA Pines, J Aronsky, D Genes, N Ginde, AA Hackman, J Hilton, JA Hwang, U Kamali, M Powell, E Sattarian, M Fu, RW AF Handel, Daniel A. Pines, Jesse Aronsky, Dominik Genes, Nicholas Ginde, Adit A. Hackman, Jeffrey Hilton, Joshua A. Hwang, Ula Kamali, Michael Powell, Emilie Sattarian, Medhi Fu, Rongwei TI Variations in Crowding and Ambulance Diversion in Nine Emergency Departments SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Scientific Assembly of the American-College-of-Emergency-Physicians CY SEP, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys ID OCCUPANCY RATE; DELAYS AB Objectives: The primary study aim was to examine the variations in crowding when an emergency department (ED) initiates ambulance diversion. Methods: This retrospective, multicenter study included nine geographically disparate EDs. Daily ED operational variables were collected during a 12-month period (January 2009 to December 2009), including total number of ED visits, mean overall length of stay (LOS), number of ED beds, and hours on ambulance diversion. The primary outcome variable was the "ED workload rate," a surrogate marker for daily ED crowding. It was calculated as the total number of daily ED visits multiplied by the overall mean LOS (in hours) and divided by the number of ED beds available for acute treatment in a given day. The primary predictor variables were ambulance diversion, as a dichotomous variable of whether or not an ED went on diversion at least once during a 24-hour period, diversion hour quintiles, and sites. Results: The annual ED census ranged from 43,000 to 101,000 patients. The percentage of days that an ED went on diversion at least once varied from 4.9% to 86.6%. On days with ambulance diversion, the mean ED workload rate varied from 17.1 to 62.1 patient LOS hours per ED bed among sites. The magnitude of variation in ED workload rate was similar on days without ambulance diversion. Differences in ED workload rate varied among sites, ranging from 1.0 to 6.0 patient LOS hours per ED bed. ED workload rate was higher on average on diversion days compared to nondiversion days. The mean difference between diversion and nondiversion was statistically significant for the majority of sites. Conclusions: There was marked variation in ED workload rates and whether or not ambulance diversion occurred during a 24-hour period. This variability in initiating ambulance diversion suggests different or inconsistently applied decision-making criteria for initiating diversion. ACADEMIC EMERGENCY MEDICINE 2011; 18: 941-946 (C) 2011 by the Society for Academic Emergency Medicine C1 [Handel, Daniel A.; Fu, Rongwei] Oregon Hlth & Sci Univ, Dept Emergency Med, Ctr Policy & Res Emergency Med, Portland, OR 97201 USA. [Pines, Jesse] George Washington Univ, Sch Med, Dept Emergency Med, Dept Hlth Policy,George Washington Sch Publ Hlth, Washington, DC USA. [Aronsky, Dominik] Vanderbilt Univ, Dept Biomed Informat & Emergency Med, Nashville, TN USA. [Genes, Nicholas; Hwang, Ula] Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. [Ginde, Adit A.] Univ Colorado, Dept Emergency Med, Denver Sch Med, Aurora, CO USA. [Hackman, Jeffrey] Univ Missouri, Truman Med Ctr, Dept Emergency Med, Kansas City, MO 64108 USA. [Hilton, Joshua A.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Hwang, Ula] James J Peters VAMC, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Kamali, Michael] Univ Rochester, Dept Emergency Med, Rochester, NY USA. [Powell, Emilie] Northwestern Univ, Dept Emergency Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Fu, Rongwei] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. RP Handel, DA (reprint author), Oregon Hlth & Sci Univ, Dept Emergency Med, Ctr Policy & Res Emergency Med, Portland, OR 97201 USA. EM handeld@ohsu.edu RI Siry, Bonnie/D-7189-2017 OI Genes, Nicholas/0000-0002-9836-2477 FU NIA NIH HHS [K24 AG022345] NR 24 TC 16 Z9 16 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD SEP PY 2011 VL 18 IS 9 BP 941 EP 946 DI 10.1111/j.1553-2712.2011.01149.x PG 6 WC Emergency Medicine SC Emergency Medicine GA 818OZ UT WOS:000294764200008 PM 21906203 ER PT J AU Bird, TD Yu, CE AF Bird, Thomas D. Yu, Chang-En TI Alois Alzheimer's Case, Auguste D., Did Not Carry the N141I Mutation in PSEN2 Characteristic of Alzheimer Disease in Volga Germans Reply SO ARCHIVES OF NEUROLOGY LA English DT Letter C1 [Bird, Thomas D.; Yu, Chang-En] Univ Washington, Geriatr Res Educ & Clin Ctr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98108 USA. RP Bird, TD (reprint author), Univ Washington, Geriatr Res Educ & Clin Ctr, Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbia Way, Seattle, WA 98108 USA. EM tomnroz@u.washington.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD SEP PY 2011 VL 68 IS 9 BP 1211 EP 1211 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 817RW UT WOS:000294693200024 ER PT J AU Demirjian, S Chertow, GM Zhang, JH O'Connor, TZ Vitale, J Paganini, EP Palevsky, PM AF Demirjian, Sevag Chertow, Glenn M. Zhang, Jane Hongyuan O'Connor, Theresa Z. Vitale, Joseph Paganini, Emil P. Palevsky, Paul M. CA VA NIH Acute Renal Failure Trial N TI Model to Predict Mortality in Critically Ill Adults with Acute Kidney Injury SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; INTENSIVE-CARE-UNIT; REPLACEMENT THERAPY; TRIAL NETWORK; CLASSIFICATION-SYSTEM; ACUTE PHYSIOLOGY; RISK-ADJUSTMENT; SCORING SYSTEMS; SEVERITY; SUPPORT AB Background and objectives Acute kidney injury (AKI) requiring dialysis is associated with high mortality. Most prognostic tools used to describe case complexity and to project patient outcome lack predictive accuracy when applied in patients with AKI. In this study, we developed an AKI-specific predictive model for 60-day mortality and compared the model to the performance of two generic (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation II [APACHE II]) scores, and a disease specific (Cleveland Clinic [CCF]) score. Design, setting, participants, & measurements Data from 1122 subjects enrolled in the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study; a multicenter randomized trial of intensive versus less intensive renal support in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 VA- and university-affiliated centers. Results The 60-day mortality was 53%. Twenty-one independent predictors of 60-day mortality were identified. The logistic regression model exhibited good discrimination, with an area under the receiver operating characteristic (ROC) curve of 0.85 (0.83 to 0.88), and a derived integer risk score yielded a value of 0.80 (0.77 to 0.83). Existing scoring systems, including APACHE II, SOFA, and CCF, when applied to our cohort, showed relatively poor discrimination, reflected by areas under the ROC curve of 0.68 (0.64 to 0.71), 0.69 (0.66 to 0.73), and 0.65 (0.62 to 0.69), respectively. Conclusions Our new risk model outperformed existing generic and disease-specific scoring systems in predicting 60-day mortality in critically ill patients with AKI. The current model requires external validation before it can be applied to other patient populations. Clin J Am Soc Nephrol 6: 2114-2120, 2011. doi:10.2215/CJN.02900311 C1 [Demirjian, Sevag; Paganini, Emil P.] Cleveland Clin, Dept Hypertens & Nephrol, Cleveland, OH 44195 USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA. [Zhang, Jane Hongyuan; O'Connor, Theresa Z.; Vitale, Joseph] VA Connecticut Healthcare Syst, Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Demirjian, S (reprint author), Cleveland Clin, Dept Hypertens & Nephrol, 9500 Euclid Ave,Q7, Cleveland, OH 44195 USA. EM demirjs@ccf.org NR 24 TC 29 Z9 32 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 SEP PY 2011 VL 6 IS 9 BP 2114 EP 2120 DI 10.2215/CJN.02900311 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 817EN UT WOS:000294654200005 PM 21896828 ER PT J AU Davison, BA Cotter, G Sun, HR Chen, L Teerlink, JR Metra, M Felker, GM Voors, AA Ponikowski, P Filippatos, G Greenberg, B Teichman, SL Unemori, E Koch, GG AF Davison, Beth A. Cotter, Gad Sun, Hengrui Chen, Li Teerlink, John R. Metra, Marco Felker, G. Michael Voors, Adriaan A. Ponikowski, Piotr Filippatos, Gerasimos Greenberg, Barry Teichman, Sam L. Unemori, Elaine Koch, Gary G. TI Permutation criteria to evaluate multiple clinical endpoints in a proof-of-concept study: lessons from Pre-RELAX-AHF SO CLINICAL RESEARCH IN CARDIOLOGY LA English DT Article DE Heart failure; Statistics; Clinical trials; Phase II ID ACUTE HEART-FAILURE; TRIALS; ROLOFYLLINE; ANTAGONIST; THERAPIES; DESIGN AB Clinically relevant endpoints cannot be routinely targeted with reasonable power in a small study. Hence, proof-of-concept studies are often powered to a primary surrogate endpoint. However, in acute heart failure (AHF) effects on surrogates have not translated into clinical benefit in confirmatory studies. Although observing an effect on one of many endpoints due to chance is likely, observing concurrent positive trends across several outcomes by chance is usually unlikely. Pre-RELAX-AHF, which compared 4 relaxin doses with placebo in AHF, has shown favourable trends versus placebo (one-sided P < 0.10) on six of nine clinical endpoints in the 30 mu g/kg/day group. To illustrate evaluation of multiple, correlated clinical endpoints for evidence of efficacy and for dose selection, a permutation method was applied retrospectively. By randomly re-assigning the treatment group to the actual data for each of the 229 subjects, 20,000 permutation samples were constructed. The permutation P value for at least six favourable trends among nine endpoints in any dose groups was 0.0073 (99.9% CI 0.0053-0.0093). This is higher than would be expected if the endpoints were uncorrelated (0.00026), but much lower than the probability of observing one of nine comparisons significant at the traditional two-sided P < 0.05 (0.74). Thus, the result was unlikely due to correlated endpoints or to chance. Examining consistency of effect across multiple clinical endpoints in a proof-of-concept study may identify efficacious therapies and enable dose selection for confirmatory trials. The merit of the approach described requires confirmation through prospective application in designing future studies. C1 [Davison, Beth A.; Cotter, Gad; Sun, Hengrui] Momentum Res Inc, Durham, NC USA. [Chen, Li; Koch, Gary G.] Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. [Teerlink, John R.] Univ Calif San Francisco, Cardiol Sect, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Metra, Marco] Univ Brescia, Dept Expt & Appl Med, Brescia, Italy. [Felker, G. Michael] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 AV Groningen, Netherlands. [Ponikowski, Piotr] Med Univ, Mil Hosp, Dept Cardiol, Dept Hlth Sci, Wroclaw, Poland. [Filippatos, Gerasimos] Univ Athens, Hosp Attikon, Athens, Greece. [Greenberg, Barry] Univ Calif San Diego, Adv Heart Failure Program, San Diego, CA 92103 USA. [Teichman, Sam L.; Unemori, Elaine] Corthera Inc, San Mateo, CA USA. RP Davison, BA (reprint author), Momentum Res Inc, Durham, NC USA. EM bethdavison@momentum-research.com RI Teerlink, John/D-2986-2012; Lainscak, Mitja/F-3237-2015; Ponikowski, Piotr/O-6454-2015 OI Ponikowski, Piotr/0000-0002-3391-7064; Davison, Beth/0000-0003-2374-6449; Metra, Marco/0000-0001-6691-8568 FU Corthera, Inc. FX The authors thank Jill El-Khorazaty, Michael Hussey, and Daniela Sotres for their review and helpful comments. Pre-RELAX-AHF was sponsored by Corthera, Inc., a subsidiary of Novartis Pharmaceuticals Corp. (San Mateo, California). NR 18 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-0684 J9 CLIN RES CARDIOL JI Clin. Res. Cardiol. PD SEP PY 2011 VL 100 IS 9 BP 745 EP 753 DI 10.1007/s00392-011-0304-5 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 817RE UT WOS:000294690900004 PM 21416190 ER PT J AU Baddley, JW Winthrop, KL Patkar, NM Delzell, E Beukelman, T Xie, FL Chen, L Curtis, JR AF Baddley, John W. Winthrop, Kevin L. Patkar, Nivedita M. Delzell, Elizabeth Beukelman, Timothy Xie, Fenglong Chen, Lang Curtis, Jeffrey R. TI Geographic Distribution of Endemic Fungal Infections among Older Persons, United States SO EMERGING INFECTIOUS DISEASES LA English DT Article ID OPPORTUNISTIC INFECTIONS; ELDERLY PERSONS; COCCIDIOIDOMYCOSIS; BLASTOMYCOSIS; HOSPITALIZATIONS; HISTOPLASMOSIS; SURVEILLANCE; SENSITIVITY; ARIZONA; USA AB To investigate the epidemiology and geographic distribution of histoplasmosis, coccidioidomycosis, and blastomycosis in older persons in the United States, we evaluated a random 5% sample of national Medicare data from 1999 through 2008. We calculated national, regional, and state-based incidence rates and determined 90-day postdiagnosis mortality rates. We identified 776 cases (357 histoplasmosis, 345 coccidioidomycosis, 74 blastomycosis). Patient mean age was 75.7 years; 55% were male. Histoplasmosis and blastomycosis incidence was highest in the Midwest (6.1 and 1.0 cases/100,000 person-years, respectively); coccidioidomycosis incidence rate was highest in the West (15.2). On the basis of available data, for 86 (11.1%) cases, there was no patient exposure to a traditional disease-endemic area. Knowledge of areas where endemic mycosis incidence is increased may affect diagnostic or prevention measures for older adults at risk. C1 [Baddley, John W.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham VA Med Ctr, Birmingham, AL USA. [Winthrop, Kevin L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Baddley, JW (reprint author), Univ Alabama, Dept Med, Div Infect Dis, 229 Tinsley Harrison Tower,1900 Univ Blvd, Birmingham, AL 35294 USA. EM jbaddley@uab.edu FU Agency for Healthcare Research and Quality [R01HS018517]; Amgen FX This study was supported by the Agency for Healthcare Research and Quality (R01HS018517). E.D. received research support from Amgen. NR 18 TC 43 Z9 45 U1 0 U2 3 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD SEP PY 2011 VL 17 IS 9 BP 1664 EP 1669 DI 10.3201/eid1709.101987 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 817FG UT WOS:000294656100012 PM 21888792 ER PT J AU Dominitz, JA Ko, CW AF Dominitz, Jason A. Ko, Cynthia W. TI Will colon capsule endoscopy replace screening colonoscopy? SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID SERVICES TASK-FORCE; COLORECTAL-CANCER C1 [Dominitz, Jason A.] Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Dominitz, JA (reprint author), Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. OI Dominitz, Jason/0000-0002-8070-7086 NR 10 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD SEP PY 2011 VL 74 IS 3 BP 590 EP 592 DI 10.1016/j.gie.2011.06.016 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 817GV UT WOS:000294660200020 PM 21872712 ER PT J AU Lomonaco, R Ortiz-Lopez, C Orsak, B Finch, J Webb, A Bril, F Louden, C Tio, F Cusi, K AF Lomonaco, Romina Ortiz-Lopez, Carolina Orsak, Beverly Finch, Joan Webb, Amy Bril, Fernando Louden, Christopher Tio, Fermin Cusi, Kenneth TI Role of Ethnicity in Overweight and Obese Patients with Nonalcoholic Steatohepatitis SO HEPATOLOGY LA English DT Article ID FATTY LIVER-DISEASE; DEPENDENT DIABETES-MELLITUS; INSULIN-RESISTANCE; HEPATIC STEATOSIS; UNITED-STATES; GLUCOSE; PIOGLITAZONE; POPULATION; PREVALENCE; SECRETION AB The role of ethnicity in determining disease severity in nonalcoholic steatohepatitis (NASH) remains unclear. We recruited 152 patients with biopsy-proven NASH, 63% of whom were Hispanic and 37% of whom were Caucasian. Both groups were well matched for age, sex, and total body fat. We measured: (1) liver fat by magnetic resonance imaging and spectroscopy; (2) fasting plasma glucose, fasting plasma insulin (FPI), and free fatty acid (FFA) levels; (3) total body fat by dual energy x-ray absorptiometry (DXA); (4) liver and muscle insulin sensitivity (insulin clamp with 3-[(3)H] glucose); (5) insulin resistance at the level of the liver (fasting endogenous glucose production derived from 3-[3H] glucose infusion x FPI) and adipose tissue (fasting FFA x FPI). Liver fat was slightly, but not significantly, higher in Hispanic vs. Caucasian patients (27 +/- 2% vs. 24 +/- 2%, p = 0.16). However, this trend did not translate into worse liver steatosis, necroinflammation or fibrosis. Patients with NASH had severe hepatic, adipose tissue and muscle insulin resistance versus healthy subjects without NASH nonalcoholic fatty liver disease, but there were no differences between both ethnic groups on these parameters. However, Hispanics versus Caucasians with type 2 diabetes mellitus (T2DM) had a trend for worse hepatic/adipose tissue insulin resistance and fibrosis. Conclusion: When Hispanic and Caucasian patients with NASH are well matched for clinical parameters, particularly for adiposity, slightly higher liver fat content is not associated with worse hepatic insulin resistance or more severe NASH on histology. Hispanic ethnicity does not appear to be a major determinant of disease severity in NASH, although those with diabetes may be at greater risk of fibrosis. Given the higher risk of T2DM in Hispanics, long-term studies are needed to define their risk of disease progression. (HEPATOLOGY 2011;54:837-845) C1 [Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, Audie L Murphy Vet Adm Med Ctr, Dept Med, Diabet Div, San Antonio, TX 78229 USA. [Webb, Amy] Univ Texas Hlth Sci Ctr San Antonio, Div Hepatol, San Antonio, TX 78229 USA. [Louden, Christopher] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Tio, Fermin] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. RP Cusi, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Audie L Murphy Vet Adm Med Ctr, Dept Med, Diabet Div, San Antonio, TX 78229 USA. EM cusi@uthscsa.edu RI webb, andrew/G-9642-2016 OI webb, andrew/0000-0003-4045-9732 FU Burroughs Wellcome Fund; American Diabetes Association [1-08-CR-08]; VA Merit Award [1 101 CX000167-01]; Veterans Affairs Medical Research Fund; National Center for Research Resources [UL IRR025767] FX Supported by the Burroughs Wellcome Fund (K. C.), the American Diabetes Association (1-08-CR-08 [K. C.]), and a VA Merit Award (1 101 CX000167-01 [K. C.]). Additional support was received from the Veterans Affairs Medical Research Fund and by Award No. UL IRR025767 from the National Center for Research Resources. NR 45 TC 37 Z9 37 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2011 VL 54 IS 3 BP 837 EP 845 DI 10.1002/hep.24483 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 818FZ UT WOS:000294738300012 PM 21674556 ER PT J AU Connick, E Bosch, RJ Aga, E Schlichtemeier, R Demeter, LM Volberding, P AF Connick, Elizabeth Bosch, Ronald J. Aga, Evgenia Schlichtemeier, Rick Demeter, Lisa M. Volberding, Paul CA ACTG 709 Team TI Augmented HIV-Specific Interferon-Gamma Responses, But Impaired Lymphoproliferation During Interruption of Antiretroviral Treatment Initiated in Primary HIV Infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE CD4-positive T lymphocytes; CD8-positive T lymphocytes; cytotoxic T lymphocytes; HIV infections; highly active antiretroviral therapy; treatment interruption ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; VIRAL REPLICATION; IMMUNE-RESPONSES; THERAPY; INDIVIDUALS; VIREMIA; TRIALS; IMMUNIZATION; ANTIGENS AB Background: Antiretroviral therapy (ART) introduced during primary HIV infection followed by treatment interruption (TI) is postulated to enhance virologic control through induction of HIV-specific CD4(+) T cells, which foster virus-specific CD8+ T cells that suppress virus replication. This hypothesis was evaluated in 21 subjects enrolled in AIDS Clinical Trials Group 709, a substudy of AIDS Clinical Trials Group 371, which prospectively evaluated subjects who received >= 1 year of ART initiated in acute or recent HIV infection followed by TI. Methods: Lymphoproliferation was assessed by [methyl-(3)H] thymidine incorporation and HIV-specific CD8+ T-cell interferon-gamma responses by enzyme-linked immunospot-forming assays. Virologic success was defined as sustained viral load <5000 copies per milliliter for 24 weeks after TI. Results: HIV-specific lymphoproliferative responses were detected at least once in 5 (24%) of 21 subjects, were generally transient, and were unrelated to HIV-specific interferon-gamma responses (P>0.4). HIV-specific CD8+ interferon-gamma responses increased after 48 weeks of ART (P = 0.03), but failed to predict virologic success (P = 0.18). Compared with seronegative subjects, lymphoproliferation to Candida, cytomegalovirus, and alloantigens was similar in HIV-infected subjects during ART, but lower during TI (P <= 0.04). Conclusions: HIV-specific CD8+ T-cell interferon-gamma responses expand during ART following primary HIV infection, but are not related to HIV-specific lymphoproliferative responses norvirologic success. Impaired non-HIV antigen-specific lymphoproliferation associated with TI suggests this strategy could be deleterious. C1 [Connick, Elizabeth; Schlichtemeier, Rick] Univ Colorado Denver, Dept Med, Div Infect Dis, Aurora, CO 80045 USA. [Bosch, Ronald J.; Aga, Evgenia] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Demeter, Lisa M.] Univ Rochester, Sch Med & Dent, Dept Med, Div Infect Dis, Rochester, NY 14642 USA. [Volberding, Paul] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Volberding, Paul] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. RP Connick, E (reprint author), Univ Colorado Denver, Dept Med, Div Infect Dis, 12700 E 19th Ave,Box B168, Aurora, CO 80045 USA. EM liz.connick@ucdenver.edu FU AIDS Clinical Trials Group, under the National Institute of Allergy and Infectious Diseases [AI-68636, AI-38858, AI 69450, AI-38855, AI-069511, AI-69432, AI-68634] FX Supported by the AIDS Clinical Trials Group, under the National Institute of Allergy and Infectious Diseases grants AI-68636, AI-38858, AI 69450, AI-38855, AI-069511, AI-69432, and AI-68634. In addition, study drugs were provided by the manufacturers including GlaxoSmithKline, Bristol Myers Squibb, Agouron/Pfizer. NR 36 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2011 VL 58 IS 1 BP 1 EP 8 DI 10.1097/QAI.0b013e318224d0c7 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 816OA UT WOS:000294610600006 PM 21637110 ER PT J AU Vongpatanasin, W Kario, K Atlas, SA Victor, RG AF Vongpatanasin, Wanpen Kario, Kazuomi Atlas, Steven A. Victor, Ronald G. TI Central Sympatholytic Drugs SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Review ID MODERATE ESSENTIAL-HYPERTENSION; SYNDROME FOLLOWING CESSATION; PLASMA-RENIN ACTIVITY; BLOOD-PRESSURE; CLINICAL PHARMACOKINETICS; THERAPEUTIC EFFICACY; WITHDRAWAL SYNDROME; CLONIDINE; GUANFACINE; METHYLDOPA AB Key Points Central sympatholytic drugs reduce blood pressure mainly by stimulating central alpha(2)-adrenergic receptors in the brainstem centers, thereby reducing sympathetic nerve activity and neuronal release of norepinephrine to the heart and peripheral circulation. This class of drugs, however, is currently used mainly as fourth-line (or beyond) drug therapy for hypertension because of side effects of drowsiness, fatigue, and dry mouth. Rebound hypertension is also another major concern in certain drugs with a short half-life, particularly in patients who are nonadherent to the regimen. Therefore, their use on a "PRN" basis for treatment of blood pressure surge in the absence of symptoms or acute target complications should also be avoided. J Clin Hypertens (Greenwich). 2011; 13: 658-661. (C)2011 Wiley Periodicals, Inc. C1 [Vongpatanasin, Wanpen] Univ Texas SW Med Ctr Dallas, Div Cardiol, Hypertens Sect, Dallas, TX 75390 USA. [Kario, Kazuomi] Jichi Med Univ, Sch Med, Dept Med, Div Cardiovasc Med, Shimotsuke, Tochigi, Japan. [Atlas, Steven A.] Mt Sinai Sch Med, James J Peters VA Med Ctr, Bronx, NY USA. [Atlas, Steven A.] Mt Sinai Sch Med, Dept Med, Bronx, NY USA. [Victor, Ronald G.] Cedars Sinai Med Ctr, Inst Heart, Los Angeles, CA 90048 USA. RP Vongpatanasin, W (reprint author), Univ Texas SW Med Ctr Dallas, Div Cardiol, Hypertens Sect, 5323 Harry Hines Blvd,U9-400, Dallas, TX 75390 USA. EM wanpen.vongpatanasin@utsouthwestern.edu NR 36 TC 10 Z9 11 U1 0 U2 2 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 SEP PY 2011 VL 13 IS 9 BP 658 EP 661 DI 10.1111/j.1751-7176.2011.00509.x PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 816KD UT WOS:000294596300006 PM 21896146 ER PT J AU Forcade, NA Parchman, ML Jorgensen, JH Du, LC Nyren, NR Trevino, LB Pena, J Mann, MW Munoz, A Trevino, SB Mortensen, EM Wickes, BL Pollock, BH Frei, CR AF Forcade, Nicolas A. Parchman, Michael L. Jorgensen, James H. Du, Liem C. Nyren, Natalie R. Trevino, Lucina B. Pena, Joel Mann, Michael W. Munoz, Abilio Trevino, Sylvia B. Mortensen, Eric M. Wickes, Brian L. Pollock, Brad H. Frei, Christopher R. TI Prevalence, Severity, and Treatment of Community-Acquired Methicillin-Resistant Staphylococcus Aureus (CA-MRSA) Skin and Soft Tissue Infections in 10 Medical Clinics in Texas: A South Texas Ambulatory Research Network (STARNet) Study SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article DE Antibiotics; CA-MRSA; Epidemiology; Practice-based Research; Soft Tissue Infections ID EMERGENCY-DEPARTMENT; TRIMETHOPRIM-SULFAMETHOXAZOLE; CLINDAMYCIN; ABSCESSES; EPIDEMIOLOGY; MANAGEMENT; CEPHALEXIN; DIAGNOSIS; THERAPY; VISITS AB Objectives: Quantify the prevalence, measure the severity, and describe treatment patterns in patients who present to medical clinics in Texas with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft-tissue infections (SSTI). Methods: Ten primary care clinics participated in this prospective, community-based study. Clinicians consented patients and collected clinical information, pictures, and wound swabs; data were processed centrally. MRSASelect (TM) was used for identification. Susceptibilities were determined via Etest (R) Results: Overall, 73 of 119 (61%) patients presenting with SSTIs meeting eligibility requirements had CA-MRSA. Among these, 49% were male, 79% were Hispanic, and 30% had diabetes. Half (56%) of the lesions were >= 5 cm in diameter. Most patients had abscesses (82%) and many reported pain scores of >= 7 of 10 (67%). Many presented with erythema (85%) or drainage (56%). Most received incision and drainage plus an antibiotic (64%). Antibiotic monotherapy was frequently prescribed: trimethoprim-sulfamethoxazole (TMP-SMX) (78%), clindamycin (4%), doxycycline (2%), and mupirocin (2%). The rest received TMP-SMX in combination with other antibiotics. TMP-SMX was frequently administered as one double-strength tablet twice daily. Isolates were 93% susceptible to clindamycin and 100% susceptible to TMP-SMX, doxycycline, vancomycin, and linezolid. Conclusions: We report a predominance of CA-MRSA SSTIs, favorable antibiotic susceptibilities, and frequent use of TMP-SMX in primary care clinics. (J Am Board Fam Med 2011;24:543-550.) C1 [Forcade, Nicolas A.; Frei, Christopher R.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Forcade, Nicolas A.; Parchman, Michael L.; Jorgensen, James H.; Mortensen, Eric M.; Wickes, Brian L.; Pollock, Brad H.; Frei, Christopher R.] Univ Texas San Antonio, Hlth Sci Ctr, Sch Med, San Antonio, TX USA. [Parchman, Michael L.; Mortensen, Eric M.] S Texas Vet Hlth Care Syst, VERDICT Hlth Serv Res Program, San Antonio, TX USA. [Du, Liem C.; Nyren, Natalie R.; Trevino, Lucina B.; Pena, Joel; Mann, Michael W.; Munoz, Abilio; Trevino, Sylvia B.] S Texas Ambulatory Res Network STARNet, San Antonio, TX USA. RP Frei, CR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Pharmacotherapy Educ & Res Ctr PERC, 7703 Floyd Curl Dr,MSC 6220, San Antonio, TX 78229 USA. EM freic@uthscsa.edu OI Mortensen, Eric/0000-0002-3880-5563 FU United States National Institutes of Health [UL1 RR025767, KL2 RR025766]; South Texas Veterans Health Care System FX Funding: This work was supported by the United States National Institutes of Health in the form of a CTSA pilot project grant (UL1 RR025767) and a KL2 career development award (KL2 RR025766), both awarded to Dr. Frei. Drs. Parchman and Mortensen were supported by the South Texas Veterans Health Care System when this work was completed. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 30 TC 26 Z9 29 U1 0 U2 8 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD SEP-OCT PY 2011 VL 24 IS 5 BP 543 EP 550 DI 10.3122/jabfm.2011.05.110073 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 817IC UT WOS:000294664300012 PM 21900437 ER PT J AU Hayes, H Parchman, ML Howard, R AF Hayes, Holly Parchman, Michael L. Howard, Ray TI A Logic Model Framework for Evaluation and Planning in a Primary Care Practice-based Research Network (PBRN) SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article DE Evaluation; Logic Model; Practice-based Research ID TIME PHYSICAL-ACTIVITY; RISK-FACTORS; SOUTH TEXAS; BARRIERS; STARNET; BEHAVIORS; SETTINGS; BENEFITS; GLUCOSE; CLINICS AB Evaluating effective growth and development of a practice-based research network (PBRN) can be challenging. The purpose of this article is to describe the development of a logic model and how the framework has been used for planning and evaluation in a primary care PBRN. An evaluation team was formed consisting of the PBRN directors, staff, and its board members. After the mission and the target audience were determined, facilitated meetings and discussions were held with stakeholders to identify the assumptions, inputs, activities, outputs, outcomes, and outcome indicators. The long-term outcomes outlined in the final logic model are 2-fold: (1) improved health outcomes of patients served by PBRN community clinicians and (2) community clinicians are recognized leaders of quality research projects. The logic model proved useful in identifying stakeholder interests and dissemination activities as an area that required more attention in the PBRN. The logic model approach is a useful planning tool and project management resource that increases the probability that the PBRN mission will be successfully implemented. (J Am Board Fam Med 2011;24:576-582.) C1 [Hayes, Holly; Parchman, Michael L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Parchman, Michael L.] S Texas Vet Hlth Care Syst, VERDICT Hlth Serv Res Program, San Antonio, TX USA. [Howard, Ray] Acad Ctr Excellence Teaching, San Antonio, TX USA. RP Hayes, H (reprint author), 7703 Floyd Curl Dr,Mail Code 7728, San Antonio, TX 78229 USA. EM hayesh@uthscsa.edu OI Parchman, Michael/0000-0001-7129-2889 FU NCRR/NIH [UL1RR025767]; South Texas Ambulatory Research Network FX Funding: Funding for this study was provided by Clinical Translational Science Award No. UL1RR025767 from NCRR/NIH to the University of Texas Health Sciences Center at San Antonio.; The authors would like to thank the members of the South Texas Ambulatory Research Network for their support and contribution to this study. NR 37 TC 15 Z9 15 U1 0 U2 5 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD SEP-OCT PY 2011 VL 24 IS 5 BP 576 EP 582 DI 10.3122/jabfm.2011.05.110043 PG 7 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 817IC UT WOS:000294664300016 PM 21900441 ER PT J AU Magbanua, MJM Roy, R Sosa, EV Weinberg, V Federman, S Mattie, MD Hughes-Fulford, M Simko, J Shinohara, K Haqq, CM Carroll, PR Chan, JM AF Magbanua, Mark Jesus M. Roy, Ritu Sosa, Eduardo V. Weinberg, Vivian Federman, Scott Mattie, Michael D. Hughes-Fulford, Millie Simko, Jeff Shinohara, Katsuto Haqq, Christopher M. Carroll, Peter R. Chan, June M. TI Gene Expression and Biological Pathways in Tissue of Men with Prostate Cancer in a Randomized Clinical Trial of Lycopene and Fish Oil Supplementation SO PLOS ONE LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; DOCOSAHEXAENOIC ACID; ACTIVE SURVEILLANCE; OXIDATIVE STRESS; CELL-GROWTH; VITAMIN-E; CORONARY ATHEROSCLEROSIS; ARACHIDONIC-ACID; BETA-CAROTENE; DNA-DAMAGE AB Background: Studies suggest that micronutrients may modify the risk or delay progression of prostate cancer; however, the molecular mechanisms involved are poorly understood. We examined the effects of lycopene and fish oil on prostate gene expression in a double-blind placebo-controlled randomized clinical trial. Methods: Eighty-four men with low risk prostate cancer were stratified based on self-reported dietary consumption of fish and tomatoes and then randomly assigned to a 3-month intervention of lycopene (n = 29) or fish oil (n = 27) supplementation or placebo (n = 28). Gene expression in morphologically normal prostate tissue was studied at baseline and at 3 months via cDNA microarray analysis. Differential gene expression and pathway analyses were performed to identify genes and pathways modulated by these micronutrients. Results: Global gene expression analysis revealed no significant individual genes that were associated with high intake of fish or tomato at baseline or after 3 months of supplementation with lycopene or fish oil. However, exploratory pathway analyses of rank-ordered genes (based on p-values not corrected for multiple comparisons) revealed the modulation of androgen and estrogen metabolism in men who routinely consumed more fish (p = 0.029) and tomato (p = 0.008) compared to men who ate less. In addition, modulation of arachidonic acid metabolism (p = 0.01) was observed after 3 months of fish oil supplementation compared with the placebo group; and modulation of nuclear factor (erythroid derived-2) factor 2 or Nrf2-mediated oxidative stress response for either supplement versus placebo (fish oil: p = 0.01, lycopene: p = 0.001). Conclusions: We did not detect significant individual genes associated with dietary intake and supplementation of lycopene and fish oil. However, exploratory analyses revealed candidate in vivo pathways that may be modulated by these micronutrients. C1 [Magbanua, Mark Jesus M.; Sosa, Eduardo V.; Federman, Scott; Mattie, Michael D.; Carroll, Peter R.; Chan, June M.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Roy, Ritu; Weinberg, Vivian] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr Biostat &, San Francisco, CA 94143 USA. [Hughes-Fulford, Millie; Simko, Jeff; Shinohara, Katsuto; Haqq, Christopher M.; Carroll, Peter R.; Chan, June M.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Hughes-Fulford, Millie] San Francisco VA Med Ctr, San Francisco, CA USA. [Simko, Jeff] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Chan, June M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Magbanua, MJM (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. EM JChan@urology.ucsf.edu FU NIH/NCI [RO1 R01CA101042]; Prostate Cancer Foundation FX NIH/NCI RO1 R01CA101042; Prostate Cancer Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 21 Z9 23 U1 4 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 1 PY 2011 VL 6 IS 9 AR e24004 DI 10.1371/journal.pone.0024004 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 817OO UT WOS:000294683900020 PM 21912659 ER PT J AU Lee, JH Gosselin, F Wynn, JK Green, MF AF Lee, Junghee Gosselin, Frederic Wynn, Jonathan K. Green, Michael F. TI How Do Schizophrenia Patients Use Visual Information to Decode Facial Emotion? SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; emotional face recognition; spatial frequency; bubbles tasks; potent information; strategy ID GENERALIZED POOR PERFORMANCE; AFFECT RECOGNITION; AFFECTIVE PROSODY; PERCEPTION; EXPRESSIONS; FACES; IMPAIRMENT; DEFICITS AB Impairment in recognizing facial emotions is a prominent feature of schizophrenia patients, but the underlying mechanism of this impairment remains unclear. This study investigated the specific aspects of visual information that are critical for schizophrenia patients to recognize emotional expression. Using the Bubbles technique, we probed the use of visual information during a facial emotion discrimination task (fear vs. happy) in 21 schizophrenia patients and 17 healthy controls. Visual information was sampled through randomly located Gaussian apertures (or "bubbles") at 5 spatial frequency scales. Online calibration of the amount of face exposed through bubbles was used to ensure 75% overall accuracy for each subject. Least-square multiple linear regression analyses between sampled information and accuracy were performed to identify critical visual information that was used to identify emotional expression. To accurately identify emotional expression, schizophrenia patients required more exposure of facial areas (i.e., more bubbles) compared with healthy controls. To identify fearful faces, schizophrenia patients relied less on bilateral eye regions at high-spatial frequency compared with healthy controls. For identification of happy faces, schizophrenia patients relied on the mouth and eye regions; healthy controls did not utilize eyes and used the mouth much less than patients did. Schizophrenia patients needed more facial information to recognize emotional expression of faces. In addition, patients differed from controls in their use of high-spatial frequency information from eye regions to identify fearful faces. This study provides direct evidence that schizophrenia patients employ an atypical strategy of using visual information to recognize emotional faces. C1 [Lee, Junghee; Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Lee, Junghee; Wynn, Jonathan K.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Gosselin, Frederic] Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada. RP Lee, JH (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. EM jungheelee@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 [MH 43929] FX National Institute of Mental Health Grant MH 43929 (PI: M.F.G.). NR 46 TC 22 Z9 24 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD SEP PY 2011 VL 37 IS 5 BP 1001 EP 1008 DI 10.1093/schbul/sbq006 PG 8 WC Psychiatry SC Psychiatry GA 815VC UT WOS:000294557100019 PM 20156852 ER PT J AU Bosworth, HB Granger, BB Mendys, P Brindis, R Burkholder, R Czajkowski, SM Daniel, JG Ekman, I Ho, M Johnson, M Kimmel, SE Liu, LZ Musaus, J Shrank, WH Buono, EW Weiss, K Granger, CB AF Bosworth, Hayden B. Granger, Bradi B. Mendys, Phil Brindis, Ralph Burkholder, Rebecca Czajkowski, Susan M. Daniel, Jodi G. Ekman, Inger Ho, Michael Johnson, Mimi Kimmel, Stephen E. Liu, Larry Z. Musaus, John Shrank, William H. Buono, Elizabeth Whalley Weiss, Karen Granger, Christopher B. TI Medication adherence: A call for action SO AMERICAN HEART JOURNAL LA English DT Article ID BLOOD-PRESSURE CONTROL; RANDOMIZED CONTROLLED-TRIAL; PRESCRIPTION DRUG LABELS; NURSE FOLLOW-UP; PHYSICIAN COMMUNICATION; TREATMENT OUTCOMES; PATIENT ADHERENCE; ELDERLY-PATIENTS; HEALTH LITERACY; AUTOMATED CALLS AB Poor adherence to efficacious cardiovascular-related medications has led to considerable morbidity, mortality, and avoidable health care costs. This article provides results of a recent think-tank meeting in which various stakeholder groups representing key experts from consumers, community health providers, the academic community, decision-making government officials (Food and Drug Administration, National Institutes of Health, etc), and industry scientists met to evaluate the current status of medication adherence and provide recommendations for improving outcomes. Below, we review the magnitude of the problem of medication adherence, prevalence, impact, and cost. We then summarize proven effective approaches and conclude with a discussion of recommendations to address this growing and significant public health issue of medication nonadherence. (Am Heart J 2011;162:412-24.) C1 [Bosworth, Hayden B.] Durham VAMC, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Bosworth, Hayden B.] Duke Univ, Sch Nursing, Dept Psychiat & Behav Sci, Durham, NC 27705 USA. [Mendys, Phil] UNC, Sch Pharm, Pfizer, US Med Affairs, Chapel Hill, NC USA. [Mendys, Phil] UNC, Sch Pharm, Div Cardiol, Chapel Hill, NC USA. [Brindis, Ralph] Oakland Kaiser Hosp, Amer Coll Cardiol, San Francisco, CA USA. [Brindis, Ralph] Oakland Kaiser Hosp, Dept Cardiol, San Francisco, CA USA. [Burkholder, Rebecca; Johnson, Mimi] Natl Consumers League, Washington, DC USA. [Czajkowski, Susan M.] Natl Inst Heart Lung & Blood Inst, NIH, Bethesda, MD USA. [Daniel, Jodi G.] US Dept HHS, Office Natl Coordinator Hlth Informat Technol, Washington, DC 20201 USA. [Ekman, Inger] Gothenburg Univ, Sahlgrenska Acad, Ctr Person Ctr Care Long Term Illness GPCC, S-41124 Gothenburg, Sweden. [Ho, Michael] Denver VA Med Ctr, Denver, CO USA. [Kimmel, Stephen E.] Univ Penn, Sch Med, Div Cardiol, Dept Med & Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Liu, Larry Z.] Pfizer Inc, New York, NY USA. [Liu, Larry Z.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Musaus, John; Buono, Elizabeth Whalley] MWV Healthcare, Richmond, VA USA. [Shrank, William H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02115 USA. [Weiss, Karen] US FDA, Washington, DC 20204 USA. [Granger, Christopher B.] Duke Univ, Div Cardiol, Dept Med, Durham, NC 27705 USA. [Bosworth, Hayden B.] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27705 USA. RP Bosworth, HB (reprint author), Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, 2424 Erwin Rd,Suite 1105,Hock Plaza, Durham, NC 27705 USA. EM hayden.bosworth@duke.edu RI Granger, Christopher/D-3458-2014 OI Granger, Christopher/0000-0002-0045-3291 FU VA HSRD career scientist award [RCS 08-027]; American Heart Association; NIH [UL1RR024128] FX This research is supported by a VA HSRD career scientist award (RCS 08-027) and an Established Investigator Award from the American Heart Association to the first author (H. B. B.). Dr. B. Granger was supported by A NIH funded CTSA grant (UL1RR024128). The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 84 TC 83 Z9 90 U1 8 U2 29 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 SEP PY 2011 VL 162 IS 3 BP 412 EP 424 DI 10.1016/j.ahj.2011.06.007 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 814JU UT WOS:000294447400002 PM 21884856 ER PT J AU Harris, BS Zhang, YH Card, L Rivera, LB Brekken, RA Bradshaw, AD AF Harris, Brett S. Zhang, Yuhua Card, Lauren Rivera, Lee B. Brekken, Rolf A. Bradshaw, Amy D. TI SPARC regulates collagen interaction with cardiac fibroblast cell surfaces SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE extracellular matrix; fibrosis; matricellular; osteonectin; secreted protein acidic and rich in cysteine ID DIASTOLIC FUNCTION ROLE; GENE-EXPRESSION; MATRIX METALLOPROTEINASES; FIBRILLAR COLLAGENS; PRESSURE-OVERLOAD; CYSTEINE SPARC; HEART-FAILURE; HYPERTROPHY; PROTEIN; DEGRADATION AB Harris BS, Zhang Y, Card L, Rivera LB, Brekken RA, Bradshaw AD. SPARC regulates collagen interaction with cardiac fibroblast cell surfaces. Am J Physiol Heart Circ Physiol 301: H841-H847, 2011. First published June 10, 2011; doi:10.1152/ajpheart.01247.2010.-Cardiac tissue from mice that do not express secreted protein acidic and rich in cysteine (SPARC) have reduced amounts of insoluble collagen content at baseline and in response to pressure overload hypertrophy compared with wild-type (WT) mice. However, the cellular mechanism by which SPARC affects myocardial collagen is not clearly defined. Although expression of SPARC by cardiac myocytes has been detected in vitro, immunohistochemistry of hearts demonstrated SPARC staining primarily associated with interstitial fibroblastic cells. Primary cardiac fibroblasts isolated from SPARC-null and WT mice were assayed for collagen I synthesis by [(3)H] proline incorporation into procollagen and by immunoblot analysis of procollagen processing. Bacterial collagenase was used to discern intracellular from extracellular forms of collagen I. Increased amounts of collagen I were found associated with SPARC-null versus WT cells, and the proportion of total collagen I detected on SPARC-null fibroblasts without propeptides [collagen-alpha(1)(I)] was higher than in WT cells. In addition, the amount of total collagen sensitive to collagenase digestion (extracellular) was greater in SPARC-null cells than in WT cells, indicating an increase in cell surface-associated collagen in the absence of SPARC. Furthermore, higher levels of collagen type V, a fibrillar collagen implicated in collagen fibril initiation, were found in SPARC-null fibroblasts. The absence of SPARC did not result in significant differences in proliferation or in decreased production of procollagen I by cardiac fibroblasts. We conclude that SPARC regulates collagen in the heart by modulating procollagen processing and interactions with fibroblast cell surfaces. These results are consistent with decreased levels of interstitial collagen in the hearts of SPARC-null mice being due primarily to inefficient collagen deposition into the extracellular matrix rather than to differences in collagen production. C1 [Zhang, Yuhua; Card, Lauren; Bradshaw, Amy D.] Med Univ S Carolina, Dept Med, Div Cardiol, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. [Harris, Brett S.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. [Harris, Brett S.] Ralph H Johnson Dept Vet Affairs Hlth Ctr, Charleston, SC USA. [Rivera, Lee B.; Brekken, Rolf A.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dept Surg, Dallas, TX 75390 USA. RP Bradshaw, AD (reprint author), Med Univ S Carolina, Dept Med, Div Cardiol, Gazes Cardiac Res Inst, 114 Doughty St,Rm 223 Gazes Strom Thurmond Res Bl, Charleston, SC 29425 USA. EM bradshad@musc.edu FU National Institutes of Health [P20-RR-16434-10, R01-CA-118240, P20-RR-017696, HL-094517]; Veterans Administration Merit Award FX This work was supported by National Institutes of Health Grants P20-RR-16434-10 (to B. S. Harris), R01-CA-118240 (to R. A. Brekken), P20-RR-017696 (to A. D. Bradshaw), and HL-094517 (to A. D. Bradshaw) and by Veterans Administration Merit Award (to A. D. Bradshaw). NR 33 TC 24 Z9 25 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 2011 VL 301 IS 3 BP H841 EP H847 DI 10.1152/ajpheart.01247.2010 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 814EX UT WOS:000294431400025 PM 21666116 ER PT J AU Greenwood, TA Lazzeroni, LC Murray, SS Cadenhead, KS Calkins, ME Dobie, DJ Green, MF Gur, RE Gur, RC Hardiman, G Kelsoe, JR Leonard, S Light, GA Nuechterlein, KH Olincy, A Radant, AD Schork, NJ Seidman, LJ Siever, LJ Silverman, JM Stone, WS Swerdlow, NR Tsuang, DW Tsuang, MT Turetsky, BI Freedman, R Braff, DL AF Greenwood, Tiffany A. Lazzeroni, Laura C. Murray, Sarah S. Cadenhead, Kristin S. Calkins, Monica E. Dobie, Dorcas J. Green, Michael F. Gur, Raquel E. Gur, Ruben C. Hardiman, Gary Kelsoe, John R. Leonard, Sherry Light, Gregory A. Nuechterlein, Keith H. Olincy, Ann Radant, Allen D. Schork, Nicholas J. Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Stone, William S. Swerdlow, Neal R. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Freedman, Robert Braff, David L. TI Analysis of 94 Candidate Genes and 12 Endophenotypes for Schizophrenia From the Consortium on the Genetics of Schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID 2 INDEPENDENT SAMPLES; CHILDHOOD-ONSET SCHIZOPHRENIA; NMDA-RECEPTOR SUBUNIT; HIGH-DENSITY FAMILIES; AMINO-ACID OXIDASE; SIB-PAIR FAMILIES; BIPOLAR DISORDER; PREPULSE INHIBITION; SUSCEPTIBILITY GENE; CHINESE POPULATION AB Objective: The authors used a custom array of 1,536 single-nucleotide polymorphisms (SNPs) to interrogate 94 functionally relevant candidate genes for schizophrenia and identify associations with 12 heritable neurophysiological and neurocognitive endophenotypes in data collected by the Consortium on the Genetics of Schizophrenia. Method: Variance-component association analyses of 534 genotyped subjects from 130 families were conducted by using Merlin software. A novel bootstrap total significance test was also developed to overcome the limitations of existing genomic multiple testing methods and robustly demonstrate significant associations in the context of complex family data and possible population stratification effects. Results: Associations with endophenotypes were observed for 46 genes of potential functional significance, with three SNPs at p < 10(-4), 27 SNPs at p < 10(-3), and 147 SNPs at p < 0.01. The bootstrap analyses confirmed that the 47 SNP-endophenotype combinations with the strongest evidence of association significantly exceeded that expected by chance alone, with 93% of these findings expected to be true. Many of the genes interact on a molecular level, and eight genes (e.g., NRG1 and ERBB4) displayed evidence for pleiotropy, revealing associations with four or more endophenotypes. The results collectively support a strong role for genes related to glutamate signaling in mediating schizophrenia susceptibility. Conclusions: This study supports use of relevant endophenotypes and the bootstrap total significance test for identifying genetic variation underlying the etiology of schizophrenia. In addition, the observation of extensive pleiotropy for some genes and singular associations for others suggests alternative, independent pathways mediating pathogenesis in the "group of schizophrenias." C1 [Braff, David L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Biomed Genom Lab, La Jolla, CA 92093 USA. San Diego VA Healthcare Syst, La Jolla, CA USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Beth Israel Deaconess Med Ctr, Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. James J Peters VA Med Ctr, New York, NY USA. RP Braff, DL (reprint author), Univ Calif San Diego, Dept Psychiat, Mail Code 0804,9500 Gilman Dr, La Jolla, CA 92093 USA. EM dbraff@ucsd.edu RI Greenwood, Tiffany/F-6356-2012; Tsuang, Debby/L-7234-2016 OI Greenwood, Tiffany/0000-0002-6080-6503; Tsuang, Debby/0000-0002-4716-1894; Lazzeroni, Laura/0000-0002-1846-6920 FU AstraZeneca; Merck; Pfizer; Ortho-McNeil Janssen Scientific Affairs; NIMH [R01-MH-065571, R01-MH-065588, R01-MH-065562, R01-MH-065707, R01-MH-065554, R01-MH-065578, R01-MH-065558, R01-MH-86135, P50-MH-086383, K01-MH-087889]; National Institute of Diabetes and Digestive and Kidney Diseases [DK-063491]; Department of Veterans Affairs, Veterans Integrated Service Network (VISN) 22; Mental Illness Research, Education, and Clinical Center; VA [478]; Department of Veterans Affairs VISN-21 Mental Illness Research, Education, and Clinical Center FX Dr. Greenwood has received unrelated support for consulting services from INFOTECH Soft. Dr. Freedman has a patent through the VA on DNA sequences in CHRNA7. Dr. Green has been a consultant for Abbott, Cypress, Dainippon Sumitomo, Lundbeck, Otsuka, Sanofi-Aventis, Takeda, and Teva, and he has been a speaker for Janssen Cilag, Otsuka, and Sunovion. Dr. Raquel Gur has received unrelated research support from AstraZeneca and Pfizer. Dr. Ruben Gur is a consultant to Johnson and Johnson and has received investigator-initiated grants from AstraZeneca, Merck, and Pfizer. Dr. Kelsoe is a consultant for AstraZeneca and Psynomics and is on a speakers bureau for Merck. Dr. Light has received unrelated support for consulting services from Allergan, Memory, and Roche. Dr. Nuechterlein reports an investigator-initiated research grant from Ortho-McNeil Janssen Scientific Affairs and consultation to Merck and Wyeth. Dr. Olincy has received unrelated research support from Lundbeck. Dr. Turetsky has received unrelated research support from AstraZeneca and Pfizer and is a consultant to Roche. The other authors report no financial relationships with commercial interests.; This study was supported by NIMH grants R01-MH-065571, R01-MH-065588, R01-MH-065562, R01-MH-065707, R01-MH-065554, R01-MH-065578, R01-MH-065558, R01-MH-86135, P50-MH-086383 (Dr. Freedman), and K01-MH-087889 (Dr. Greenwood); by grant DK-063491 from the National Institute of Diabetes and Digestive and Kidney Diseases (Dr. Hardiman); by the Department of Veterans Affairs, Veterans Integrated Service Network (VISN) 22, Mental Illness Research, Education, and Clinical Center (Dr. Braff); by a NARSAD Distinguished Investigator Award (Dr. Braff); and by additional salary support of Dr. Lazzeroni from VA Cooperative Studies Program study 478 and the Department of Veterans Affairs VISN-21 Mental Illness Research, Education, and Clinical Center. NR 134 TC 133 Z9 136 U1 2 U2 15 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 SEP PY 2011 VL 168 IS 9 BP 930 EP 946 DI 10.1176/appi.ajp.2011.10050723 PG 17 WC Psychiatry SC Psychiatry GA 814VA UT WOS:000294484100013 PM 21498463 ER PT J AU Chitsaz, S Jaussaud, N Chau, E Yan, KS Azadani, AN Ratcliffe, MB Tseng, EE AF Chitsaz, Sam Jaussaud, Nicolas Chau, Edward Yan, Kimberly S. Azadani, Ali N. Ratcliffe, Mark B. Tseng, Elaine E. TI Operative Risks and Survival in Veterans With Severe Aortic Stenosis: Surgery Versus Medical Therapy SO ANNALS OF THORACIC SURGERY LA English DT Article ID VALVULAR HEART-DISEASE; VALVE-REPLACEMENT; ELDERLY-PATIENTS; NATURAL-HISTORY; INTERVENTIONS; IMPLANTATION; OUTCOMES AB Background. Transcatheter aortic valves were developed as an alternative to surgery for the one third to two thirds of patients with severe aortic stenosis who do not undergo aortic valve replacement. In this study, we examined reasons for medical management of aortic stenosis in relation to operative risks and outcomes for veterans with and without valve replacement. Methods. The echocardiography database was screened from 2000 to 2007 for severe aortic stenosis. The Society of Thoracic Surgeons risk scores and survival were determined for patients with and without aortic valve replacement. Results. Of 132 severe aortic stenosis patients included, 42% were medically managed. Predicted operative mortality risk was lower for surgical patients than for medical patients (4.5% +/- 4.2% versus 6.8% +/- 5.1%, p = 0.002). Overall, the most common reason for medical management of aortic stenosis was assumption that the patient was high risk for surgery (30.4%). The surgery group had significantly higher median survival (92.2 versus 32.4 months) and 5-year survival (71% versus 37%, p < 0.001) than the medical group. Cardiac surgery was not consulted in 61% of medically managed patients, of whom only 18% had Society of Thoracic Surgeons risk score of 10 or greater. Aortic valve replacement was an independent predictor of lower mortality (hazard ratio 0.43, p = 0.008). Conclusions. Although operative risk was higher among patients who did not undergo surgery, most were not the 10% or greater required for transcatheter valves. Given the significantly lower survival with medical therapy, aortic valve replacement should be carefully considered for most severe aortic stenosis patients whereas transcatheter aortic valves should be reserved for patients with high operative risks. (Ann Thorac Surg 2011;92:866-72) (C) 2011 by The Society of Thoracic Surgeons C1 Univ Calif San Francisco, Dept Surg, Med Ctr, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Tseng, EE (reprint author), UCSF Med Ctr, 500 Parnassus Ave,Ste W405,Box 0118, San Francisco, CA 94143 USA. EM elaine.tseng@ucsfmedctr.org RI Chitsaz, Sam/C-4586-2008 FU American Heart Association; Northern California Institute for Research and Education; Federation Francaise de Cardiologie/Societe Francaise de Cardiologie; Societe Francaise de Chirurugie Thoracique et Cardio-Vasculaire FX This work was supported by the American Heart Association, the Northern California Institute for Research and Education, and the Federation Francaise de Cardiologie/Societe Francaise de Cardiologie, and Societe Francaise de Chirurugie Thoracique et Cardio-Vasculaire. NR 18 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2011 VL 92 IS 3 BP 866 EP 872 DI 10.1016/j.athoracsur.2011.04.028 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 811WJ UT WOS:000294247400024 PM 21871271 ER PT J AU Wenk, JF Eslami, P Zhang, ZH Xu, C Kuhl, E Gorman, JH Robb, JD Ratcliffe, MB Gorman, RC Guccione, JM AF Wenk, Jonathan F. Eslami, Parastou Zhang, Zhihong Xu, Chun Kuhl, Ellen Gorman, Joseph H., III Robb, J. Daniel Ratcliffe, Mark B. Gorman, Robert C. Guccione, Julius M. TI A Novel Method for Quantifying the In-Vivo Mechanical Effect of Material Injected Into a Myocardial Infarction SO ANNALS OF THORACIC SURGERY LA English DT Article ID LEFT-VENTRICULAR ANEURYSM; FINITE-ELEMENT MODEL; CANINE LEFT-VENTRICLE; STRESS-ANALYSIS; CONTRACTION; PATTERNS; STRAIN; MUSCLE; HEART AB Background. Infarcted regions of myocardium exhibit functional impairment ranging in severity from hypokinesis to dyskinesis. We sought to quantify the effects of injecting a calcium hydroxyapatite-based tissue filler on the passive material response of infarcted left ventricles. Methods. Three-dimensional finite element models of the left ventricle were developed using three-dimensional echocardiography data from sheep with a treated and untreated anteroapical infarct, to estimate the material properties (stiffness) in the infarct and remote regions. This was accomplished by matching experimentally determined left ventricular volumes, and minimizing radial strain in the treated infarct, which is indicative of akinesia. The nonlinear stress-strain relationship for the diastolic myocardium was anisotropic with respect to the local muscle fiber direction, and an elastance model for active fiber stress was incorporated. Results. It was found that the passive stiffness parameter, C, in the treated infarct region is increased by nearly 345 times the healthy remote value. Additionally, the average myofiber stress in the treated left ventricle was significantly reduced in both the remote and infarct regions. Conclusions. Overall, injection of tissue filler into the infarct was found to render it akinetic and reduce stress in the left ventricle, which could limit the adverse remodeling that leads to heart failure. (Ann Thorac Surg 2011;92:935-41) (C) 2011 by The Society of Thoracic Surgeons C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. Dept Vet Affairs Med Ctr, San Francisco, CA USA. Univ Penn, Gorman Cardiovasc Res Grp, Philadelphia, PA 19104 USA. Stanford Univ, Dept Mech Engn, Palo Alto, CA 94304 USA. RP Guccione, JM (reprint author), San Francisco VA Med Ctr, Div Surg Serv 112D, 4150 Clement St, San Francisco, CA 94121 USA. EM guccionej@surgery.ucsf.edu RI Kuhl, Ellen/G-4444-2011 OI Kuhl, Ellen/0000-0002-6283-935X FU National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD [HL84431, HL86400, HL63348, HL77921, HL99172]; American Heart Association, Dallas, TX FX This work was supported by grants from the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD (HL84431, HL86400, HL63348, HL77921, and HL99172). Drs Robert Gorman and Joseph Gorman are supported by individual Established Investigator Awards from the American Heart Association, Dallas, TX. NR 28 TC 30 Z9 30 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2011 VL 92 IS 3 BP 935 EP 941 DI 10.1016/j.athoracsur.2011.04.089 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 811WJ UT WOS:000294247400035 PM 21871280 ER PT J AU Brody, AL Mandelkern, MA London, ED Khan, A Kozman, D Costello, MR Vellios, EE Archie, MM Bascom, R Mukhin, AG AF Brody, Arthur L. Mandelkern, Mark A. London, Edythe D. Khan, Aliyah Kozman, Daniel Costello, Matthew R. Vellios, Evan E. Archie, Meena M. Bascom, Rebecca Mukhin, Alexey G. TI Effect of Secondhand Smoke on Occupancy of Nicotinic Acetylcholine Receptors in Brain SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; INFANT-DEATH-SYNDROME; CIGARETTE-SMOKE; PASSIVE SMOKING; BINDING-PROPERTIES; IN-VITRO; PET; EXPOSURE; DEPENDENCE; BLOOD AB Context: Despite progress in tobacco control, secondhand smoke (SHS) exposure remains prevalent worldwide and is implicated in the initiation and maintenance of cigarette smoking. Objective: To determine whether moderate SHS exposure results in brain alpha(4)beta(2)* nicotinic acetylcholine receptor (nAChR) occupancy. Design, Setting, and Participants: Positron emission tomography scanning and the radiotracer 2-[18F]fluoro-3-(2(S)azetidinylmethoxy) pyridine (also known as 2-[(18)F]fluoro-A-85380, or 2-FA) were used to determine alpha(4)beta(2)* nAChR occupancy from SHS exposure in 24 young adult participants (11 moderately dependent cigarette smokers and 13 nonsmokers). Participants underwent two bolus-plus-continuous-infusion 2-FA positron emission tomography scanning sessions during which they sat in the passenger's seat of a car for 1 hour and either were exposed to moderate SHS or had no SHS exposure. The study took place at an academic positron emission tomography center. Main Outcome Measure: Changes induced by SHS in 2-FA specific binding volume of distribution as a measure of alpha(4)beta(2)* nAChR occupancy. Results: An overall multivariate analysis of variance using specific binding volume of distribution values revealed a significant main effect of condition (SHS vs control) (F(1,22)=42.5, P<.001) but no between-group (smoker vs nonsmoker) effect. Exposure to SHS led to a mean 19% occupancy of brain alpha(4)beta(2)* nAChRs (1-sample t test, 2-tailed, P<.001). Smokers had both a mean 23% increase in craving with SHS exposure and a correlation between thalamic alpha(4)beta(2)* nAChR occupancy and craving alleviation with subsequent cigarette smoking (Spearman rho=-0.74, P=.01). Conclusions: Nicotine from SHS exposure results in substantial brain alpha(4)beta(2)* nAChR occupancy in smokers and nonsmokers. Study findings suggest that such exposure delivers a priming dose of nicotine to the brain that contributes to continued cigarette use in smokers. This study has implications for both biological research into the link between SHS exposure and cigarette use and public policy regarding the need to limit SHS exposure in cars and other enclosed spaces. C1 [Brody, Arthur L.; London, Edythe D.; Khan, Aliyah; Kozman, Daniel; Costello, Matthew R.; Vellios, Evan E.; Archie, Meena M.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. [Brody, Arthur L.; Mandelkern, Mark A.; London, Edythe D.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Radiol, Los Angeles, CA USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. [Bascom, Rebecca] Penn State Univ, Dept Pulmonol, Hershey, PA USA. [Mukhin, Alexey G.] Duke Univ, Dept Psychiat, Durham, NC 27706 USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Behav Sci, 300 UCLA Med Plaza,Ste 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu FU Philip Morris USA; Tobacco-Related Disease Research Program [16RT-0098]; National Institute on Drug Abuse [R01 DA20872]; Veterans Affairs Type I Merit Review Award; Office of National Drug Control Policy [DABT63-00-C-1003] FX Drs London and Mukhin received support from Philip Morris USA for research other than the project presented here.; This study was supported by grant 16RT-0098 from the Tobacco-Related Disease Research Program (Dr Brody), grant R01 DA20872 from the National Institute on Drug Abuse (Dr Brody), a Veterans Affairs Type I Merit Review Award (Dr Brody), grant DABT63-00-C-1003 from the Office of National Drug Control Policy (Dr London), and endowments from the Richard Metzner Chair in Clinical Neuropharmacology (Dr Brody), the Thomas P. and Katherine K. Pike Chair in Addiction Studies (Dr London), and the Marjorie Greene Family Trust (Dr London). NR 70 TC 25 Z9 26 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 2011 VL 68 IS 9 BP 953 EP 960 DI 10.1001/archgenpsychiatry.2011.51 PG 8 WC Psychiatry SC Psychiatry GA 815OU UT WOS:000294535700011 PM 21536968 ER PT J AU Li, G Wang, LY Shofer, JB Thompson, ML Peskind, ER McCormick, W Bowen, JD Crane, PK Larson, EB AF Li, Ge Wang, Lucy Y. Shofer, Jane B. Thompson, Mary Lou Peskind, Elaine R. McCormick, Wayne Bowen, James D. Crane, Paul K. Larson, Eric B. TI Temporal Relationship Between Depression and Dementia Findings From a Large Community-Based 15-Year Follow-up Study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; WHITE-MATTER LESIONS; LATE-LIFE DEPRESSION; ALZHEIMER-DISEASE; MAJOR DEPRESSION; RISK-FACTOR; CES-D; SYMPTOMS; COMMUNITY; DECLINE AB Context: Late-life depression is associated with increased risk of dementia, but the temporal relationship between depression and development of dementia remains unclear. Objectives: To examine the association between risk of dementia and baseline depressive symptoms; history of depression, particularly early-life (<50 years) vs late-life depression (>= 50 years); and individual domains of the Center for Epidemiologic Studies Depression Scale. Design: A large cohort with initially nondemented participants was followed up biennially for up to 15 years. Baseline depressive symptoms were assessed using the 11-item version of the Center for Epidemiologic Studies Depression Scale; presence of significant depressive symptoms was defined as a score of 11 or greater. Self-reported history of depression was collected at the baseline interview. Cox proportional hazards regression was used to assess the association between depression and dementia risk. Setting: Population-based cohort drawn from members of the Group Health Cooperative in Seattle, Washington. Participants: A cohort of 3410 participants without dementia aged at least 65 years. Results: During a mean of 7.1 years of follow-up, 658 participants (19.3%) developed dementia. At baseline, 9.4% of participants had presence of significant depressive symptoms, and 21.2% reported a history of depression. The adjusted hazard ratio for dementia associated with baseline depressive symptoms was 1.71 (95% confidence interval, 1.37-2.13), after adjusting for age at entry, sex, educational level, and wave of enrollment. Compared with participants without depression history, those with late-life depression were at increased dementia risk (adjusted hazard ratio, 1.46; 95% confidence interval, 1.16-1.84), but early-life depression had no association with dementia risk (1.10 [0.83-1.47]). Depressed mood (adjusted hazard ratio, 1.48; 95% confidence interval, 1.25-1.76) and perceived performance difficulty (1.39 [1.15-1.67]) were independently associated with dementia. Conclusion: This study confirmed that late-life depression is associated with increased risk of dementia and supplied evidence that late-life depression may be an early manifestation of dementia rather than increasing risk for dementia. C1 [Li, Ge; Wang, Lucy Y.; Peskind, Elaine R.] VA Puget Sound Hlth Care Syst, Mental Illness Res & Educ Clin Ctr, Seattle, WA 98108 USA. [Li, Ge; Wang, Lucy Y.; Shofer, Jane B.; Peskind, Elaine R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Thompson, Mary Lou] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [McCormick, Wayne; Crane, Paul K.; Larson, Eric B.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Bowen, James D.] Swedish Med Ctr, Swedish Neurosci Inst, Englewood, CO 80110 USA. [Larson, Eric B.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. RP Li, G (reprint author), VA Puget Sound Hlth Care Syst, Mental Illness Res & Educ Clin Ctr, 1660 S Columbian Way,Mail Code S-116-6-E, Seattle, WA 98108 USA. EM gli@u.washington.edu RI Crane, Paul/C-8623-2014 OI Crane, Paul/0000-0003-4278-7465 FU National Institute of Aging [AG033693, AG006781, AG05136]; Department of Veterans Affairs; VA Puget Sound Health Care System FX This study was supported by grants AG033693, AG006781, and AG05136 from the National Institute of Aging and by the Department of Veterans Affairs and partially supported by resources from the VA Puget Sound Health Care System. NR 38 TC 41 Z9 44 U1 2 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 2011 VL 68 IS 9 BP 970 EP 977 PG 8 WC Psychiatry SC Psychiatry GA 815OU UT WOS:000294535700013 PM 21893662 ER PT J AU Gesty-Palmer, D Luttrell, LM AF Gesty-Palmer, Diane Luttrell, Louis M. TI 'Biasing' the parathyroid hormone receptor: A novel anabolic approach to increasing bone mass? SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Review DE G-protein-coupled receptor (GPCR); GPCR signalling; beta-arrestin; biased agonism; functional selectivity; parathyroid hormone (PTH); type I parathyroid hormone receptor (PTH1R); bone metabolism; osteoporosis ID PROTEIN-COUPLED RECEPTORS; RAT OSTEOBLASTIC CELLS; C ACTIVATION DOMAIN; BETA-ARRESTIN; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; DEPENDENT PATHWAYS; GROWTH-HORMONE; KIDNEY-CELLS; KINASE AB 'Functional selectivity' refers to the ability of a ligand to activate and/or inhibit only a subset of the signals capable of emanating from its cognate G-protein-coupled receptor (GPCR). Whereas conventional GPCR agonism and antagonism can be viewed as modulating the quantity of efficacy, functionally selective or 'biased' ligands qualitatively change the nature of information flow across the plasma membrane, raising the prospect of drugs with improved therapeutic efficacy or reduced side effects. Nonetheless, there is little experimental evidence that biased ligands offer advantages over conventional agonists/antagonists in vivo. Recent work with the type I parathyroid hormone receptor (PTH(1)R) suggests that biased ligands that selectively activate G-protein-independent arrestin-mediated signalling pathways may hold promise in the treatment of osteoporosis. Parathyroid hormone (PTH) is a principle regulator of bone and calcium metabolism. In bone, PTH exerts complex effects; promoting new bone formation through direct actions on osteoblasts while simultaneously stimulating bone loss through indirect activation of osteoclastic bone resorption. Although the conventional PTH(1)R agonist teriparatide, PTH(1-34), is effective in the treatment of osteoporosis, its utility is limited by its bone-resorptive effects and propensity to promote hypercalcaemia/hypercalcuria. In contrast, D-Trp(12),Tyr(34)-bPTH(7-34) (PTH-beta arr), an arrestin pathway-selective agonist for the PTH(1)R, induces anabolic bone formation independent of classic G-protein-coupled signalling mechanisms. Unlike PTH(1-34), PTH-beta arr appears to 'uncouple' the anabolic effects of PTH1R activation from its catabolic and calcitropic effects. Such findings offer evidence that arrestin pathway-selective GPCR agonists can elicit potentially beneficial effects in vivo that cannot be achieved using conventional agonist or antagonist ligands. C1 [Gesty-Palmer, Diane] Duke Univ, Med Ctr, Dept Med, Div Endocrinol & Metab, Durham, NC 27710 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Gesty-Palmer, Diane] Durham Vet Affairs Med Ctr, Durham, NC USA. [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Gesty-Palmer, D (reprint author), Duke Univ, Med Ctr, Dept Med, Div Endocrinol & Metab, Box 103015, Durham, NC 27710 USA. EM gesty001@mc.duke.edu FU National Institutes of Health [DK64353, DK55524, HD043446]; Arthritis Foundation; Research Services of the Charleston, SC and Durham, NC Veterans Affairs Medical Centers FX This work was supported by National Institutes of Health Grants DK64353 (LML, DGP), DK55524 (LML) and HD043446 (DGP); the Arthritis Foundation (DGP) and the Research Services of the Charleston, SC and Durham, NC Veterans Affairs Medical Centers. NR 66 TC 19 Z9 20 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD SEP PY 2011 VL 164 IS 1 BP 59 EP 67 DI 10.1111/j.1476-5381.2011.01450.x PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 810LL UT WOS:000294126700005 PM 21506957 ER PT J AU Hornsby, BWY Johnson, EE Picou, E AF Hornsby, Benjamin W. Y. Johnson, Earl E. Picou, Erin TI Effects of Degree and Configuration of Hearing Loss on the Contribution of High- and Low-Frequency Speech Information to Bilateral Speech Understanding SO EAR AND HEARING LA English DT Article ID THAN-NORMAL LEVELS; DEAD REGIONS; IMPAIRED LISTENERS; ARTICULATION INDEX; CONSONANT RECOGNITION; WORD RECOGNITION; NOISE; AUDIBILITY; AMPLIFICATION; INTELLIGIBILITY AB Objectives: The purpose of this study was to examine the effects of degree and configuration of hearing loss on the use of, and benefit from, information in amplified high- and low-frequency speech presented in background noise. Design: Sixty-two adults with a wide range of high-and low-frequency sensorineural hearing loss (5 to 115+ dB HL) participated in the study. To examine the contribution of speech information in different frequency regions, speech understanding in noise was assessed in multiple low-and high-pass filter conditions, as well as a band-pass (713 to 3534 Hz) and wideband (143 to 8976 Hz) condition. To increase audibility over a wide frequency range, speech and noise were amplified based on each individual's hearing loss. A stepwise multiple linear regression approach was used to examine the contribution of several factors to (1) absolute performance in each filter condition and (2) the change in performance with the addition of amplified high-and low-frequency speech components. Results: Results from the regression analysis showed that degree of hearing loss was the strongest predictor of absolute performance for low-and high-pass filtered speech materials. In addition, configuration of hearing loss affected both absolute performance for severely low-pass filtered speech and benefit from extending high-frequency (3534 to 8976 Hz) bandwidth. Specifically, individuals with steeply sloping high-frequency losses made better use of low-pass filtered speech information than individuals with similar low-frequency thresholds but less high-frequency loss. In contrast, given similar high-frequency thresholds, individuals with flat hearing losses received more benefit from extending high-frequency bandwidth than individuals with more sloping losses. Conclusions: Consistent with previous work, benefit from speech information in a given frequency region generally decreases as degree of hearing loss in that frequency region increases. However, given a similar degree of loss, the configuration of hearing loss also affects the ability to use speech information in different frequency regions. Except for individuals with steeply sloping high-frequency losses, providing high-frequency amplification (3534 to 8976 Hz) had either a beneficial effect on, or did not significantly degrade, speech understanding. These findings highlight the importance of extended high-frequency amplification for listeners with a wide range of high-frequency hearing losses, when seeking to maximize intelligibility. C1 [Hornsby, Benjamin W. Y.; Picou, Erin] Vanderbilt Univ, Vanderbilt Bill Wilkerson Ctr, Dan Maddox Hearing Aid Res Lab, Dept Hearing & Speech Sci, Nashville, TN 37232 USA. [Johnson, Earl E.] US Dept Vet Affairs, Mountain Home, TN USA. [Johnson, Earl E.] E Tennessee State Univ, Dept Communicat Disorders, Mountain Home, TN USA. RP Hornsby, BWY (reprint author), Vanderbilt Univ, Vanderbilt Bill Wilkerson Ctr, Dan Maddox Hearing Aid Res Lab, Dept Hearing & Speech Sci, Room 8310 Med Ctr E,South Tower,1215 21st Ave S, Nashville, TN 37232 USA. EM ben.hornsby@vanderbilt.edu FU National Institute on Deafness and Other Communication Disorders (National Institutes of Health) [R03 DC006576]; Dan Maddox Hearing Aid Research Foundation FX This work was supported, in part, by Grant R03 DC006576 from the National Institute on Deafness and Other Communication Disorders (National Institutes of Health) and the Dan Maddox Hearing Aid Research Foundation. NR 47 TC 23 Z9 26 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD SEP-OCT PY 2011 VL 32 IS 5 BP 543 EP 555 DI 10.1097/AUD.0b013e31820e5028 PG 13 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 812HI UT WOS:000294281400001 PM 21336138 ER PT J AU Hill-Burns, EM Hamza, TH Zabetian, CP Factor, SA Payami, H AF Hill-Burns, E. M. Hamza, T. H. Zabetian, C. P. Factor, S. A. Payami, H. TI An attempt to replicate interaction between coffee and CYP1A2 gene in connection to Parkinson's disease SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Letter DE coffee; CYP1A2; Parkinson's disease ID CAFFEINE; SMOKING; RISK C1 [Hill-Burns, E. M.; Hamza, T. H.; Payami, H.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Zabetian, C. P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Zabetian, C. P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Factor, S. A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Payami, H (reprint author), New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. EM hpayami@wadsworth.org OI Zabetian, Cyrus/0000-0002-7739-4306 FU NINDS NIH HHS [R01 NS036960] NR 6 TC 3 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2011 VL 18 IS 9 BP E107 EP E108 DI 10.1111/j.1468-1331.2011.03464.x PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 813DO UT WOS:000294347200001 PM 21834891 ER PT J AU Tang, HB Lee, M Budak, MT Pietras, N Hittinger, S Vu, M Khuong, A Hoang, CD Hussain, SNA Levine, S Shrager, JB AF Tang, Huibin Lee, Myung Budak, Murat T. Pietras, Nicole Hittinger, Scott Vu, Michael Khuong, Andy Hoang, Chuong D. Hussain, Sabah N. A. Levine, Sanford Shrager, Joseph B. TI Intrinsic apoptosis in mechanically ventilated human diaphragm: linkage to a novel Fos/FoxO1/Stat3-Bim axis SO FASEB JOURNAL LA English DT Article DE oxidative stress; skeletal muscle; dysfunction; atrophy; respiratory muscle ID MUSCLE PROTEIN-DEGRADATION; REGIONAL WEANING CENTER; CONTRACTILE PROPERTIES; CATABOLIC CONDITIONS; OXIDATIVE STRESS; SKELETAL-MUSCLE; GENE-EXPRESSION; RAT DIAPHRAGM; CARE-UNIT; DYSFUNCTION AB Mechanical ventilation (MV) is a life-saving measure in many critically ill patients. However, prolonged MV results in diaphragm dysfunction that contributes to the frequent difficulty in weaning patients from the ventilator. The molecular mechanisms underlying ventilator-induced diaphragm dysfunction (VIDD) remain poorly understood. We report here that MV induces myonuclear DNA fragmentation (3-fold increase; P<0.01) and selective activation of caspase 9 (P<0.05) and Bcl2-interacting mediator of cell death (Bim; 2- to 7-fold increase; P<0.05) in human diaphragm. MV also statistically significantly down-regulates mitochondrial gene expression and induces oxidative stress. In cultured muscle cells, we show that oxidative stress activates each of the catabolic pathways thought to underlie VIDD: apoptotic (P<0.05), proteasomal (P<0.05), and autophagic (P<0.01). Further, silencing Bim expression blocks (P<0.05) oxidative stress-induced apoptosis. Overlapping the gene expression profiles of MV human diaphragm and H(2)O(2)-treated muscle cells, we identify Fos, FoxO1, and Stat3 as regulators of Bim expression as well as of expression of the catabolic markers atrogin and LC3. We thus identify a novel Fos/FoxO1/Stat3-Bim intrinsic apoptotic pathway and establish the centrality of oxidative stress in the development of VIDD. This information may help in the design of specific drugs to prevent this condition.-Tang, H., Lee, M., Budak, M. T., Pietras, N., Hittinger, S., Vu, M., Khuong, A., Hoang, C. D., Hussain, S. N. A., Levine, S., Shrager, J. B. Intrinsic apoptosis in mechanically ventilated human diaphragm: linkage to a novel Fos/FoxO1/Stat3-Bim axis. FASEB J. 25, 2921-2936 (2011). www.fasebj.org C1 [Tang, Huibin; Lee, Myung; Pietras, Nicole; Hittinger, Scott; Vu, Michael; Khuong, Andy; Hoang, Chuong D.; Shrager, Joseph B.] Stanford Univ, Sch Med, Dept Cardiothorac Surg, Div Thorac Surg, Stanford, CA 94305 USA. [Tang, Huibin; Lee, Myung; Pietras, Nicole; Hittinger, Scott; Vu, Michael; Khuong, Andy; Hoang, Chuong D.; Shrager, Joseph B.] Vet Affairs Palo Alto Healthcare Syst, Palo Alto, CA USA. [Budak, Murat T.; Levine, Sanford] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Budak, Murat T.; Levine, Sanford] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Hussain, Sabah N. A.] McGill Univ, Royal Victoria Hosp, Div Resp, Montreal, PQ H3A 1A1, Canada. [Hussain, Sabah N. A.] McGill Univ, Royal Victoria Hosp, Crit Care Div, Montreal, PQ H3A 1A1, Canada. RP Shrager, JB (reprint author), Stanford Univ, Sch Med, Dept Cardiothorac Surg, Div Thorac Surg, 300 Pasteur Dr, Stanford, CA 94305 USA. EM shrager@stanford.edu RI Budak, Murat/I-8358-2013 OI Budak, Murat/0000-0002-5059-9651 FU Veterans Affairs; U.S. National Institutes of Health [HL078834] FX The authors thank Kevin Hoang (summer student at University of California, San Diego, CA, USA) and Donna Minagawa (Stanford University) for technical assistance and Xiaohua Zhang (Stanford University) for assistance in bioinformatics analysis. This research was supported by a Veterans Affairs merit review grant awarded to J.B.S. and also in part by U.S. National Institutes of Health grant HL078834. The authors declare that they have no financial relationship with a commercial entity. NR 67 TC 29 Z9 29 U1 0 U2 2 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 SEP PY 2011 VL 25 IS 9 BP 2921 EP 2936 DI 10.1096/fj.11-183798 PG 16 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 814GD UT WOS:000294435200008 PM 21597002 ER PT J AU Roark, B Mitchell, M Hosom, JP Hollingshead, K Kaye, J AF Roark, Brian Mitchell, Margaret Hosom, John-Paul Hollingshead, Kristy Kaye, Jeffrey TI Spoken Language Derived Measures for Detecting Mild Cognitive Impairment SO IEEE TRANSACTIONS ON AUDIO SPEECH AND LANGUAGE PROCESSING LA English DT Article DE Forced alignment; linguistic complexity; mild cognitive impairment (MCI); parsing; spoken language understanding ID ALZHEIMERS-DISEASE; COMPLEXITY; SPEECH; SYNTAX AB Spoken responses produced by subjects during neuropsychological exams can provide diagnostic markers beyond exam performance. In particular, characteristics of the spoken language itself can discriminate between subject groups. We present results on the utility of such markers in discriminating between healthy elderly subjects and subjects with mild cognitive impairment (MCI). Given the audio and transcript of a spoken narrative recall task, a range of markers are automatically derived. These markers include speech features such as pause frequency and duration, and many linguistic complexity measures. We examine measures calculated from manually annotated time alignments (of the transcript with the audio) and syntactic parse trees, as well as the same measures calculated from automatic (forced) time alignments and automatic parses. We show statistically significant differences between clinical subject groups for a number of measures. These differences are largely preserved with automation. We then present classification results, and demonstrate a statistically significant improvement in the area under the ROC curve (AUC) when using automatic spoken language derived features in addition to the neuropsychological test scores. Our results indicate that using multiple, complementary measures can aid in automatic detection of MCI. C1 [Roark, Brian; Hosom, John-Paul] Oregon Hlth & Sci Univ, Dept Biomed Engn, Ctr Spoken Language Understanding, Portland, OR 97239 USA. [Mitchell, Margaret] Univ Aberdeen, Dept Comp Sci, Aberdeen AB24 3UE, Scotland. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97239 USA. [Kaye, Jeffrey] Portland VA Med Ctr, Portland, OR USA. RP Roark, B (reprint author), Oregon Hlth & Sci Univ, Dept Biomed Engn, Ctr Spoken Language Understanding, Portland, OR 97239 USA. EM roark@cslu.ogi.edu; m.mitchell@abdn.ac.uk; hosom@cslu.ogi.edu; hollingk@gmail.com; kaye@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU National Science Foundation (NSF) [IIS-0447214, BCS-0826654]; National Institute of Health/National Institute of Aging (NIH/NIA) [P30AG08017, R01AG024059]; Oregon Center for Aging and Technology (ORCATECH, NIH) [1P30AG024978-01]; Oregon Partnership for Alzheimer's Research FX Manuscript received August 06, 2010; revised November 05, 2010; accepted January 17, 2011. Date of publication February 07, 2011; date of current version July 20, 2011. This research was supported in part by the National Science Foundation (NSF) under Grants #IIS-0447214 and #BCS-0826654, National Institute of Health/National Institute of Aging (NIH/NIA) grants #P30AG08017 and #R01AG024059, and pilot grants from the Oregon Center for Aging and Technology (ORCATECH, NIH #1P30AG024978-01) and the Oregon Partnership for Alzheimer's Research. Any opinions, findings, conclusions or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the NSF or NIH. The associate editor coordinating the review of this manuscript and approving it for publication was Dr. Gokhan Tur. NR 44 TC 36 Z9 37 U1 1 U2 9 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1558-7916 J9 IEEE T AUDIO SPEECH JI IEEE Trans. Audio Speech Lang. Process. PD SEP PY 2011 VL 19 IS 7 BP 2081 EP 2090 DI 10.1109/TASL.2011.2112351 PG 10 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 805NL UT WOS:000293734500020 PM 22199464 ER PT J AU Wright, JD Neugut, AI Wilde, ET Buono, DL Malin, J Tsai, WY Hershman, DL AF Wright, Jason D. Neugut, Alfred I. Wilde, Elizabeth T. Buono, Donna L. Malin, Jennifer Tsai, Wei Y. Hershman, Dawn L. TI Physician Characteristics and Variability of Erythropoiesis-Stimulating Agent Use Among Medicare Patients With Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; PATIENTS RECEIVING CHEMOTHERAPY; OFF-LABEL USE; UNITED-STATES; AMERICAN SOCIETY; EORTC GUIDELINES; ANEMIC PATIENTS; BREAST-CANCER; PATTERNS; ONCOLOGY AB Purpose Drugs are usually approved for a specific indication on the basis of randomized trials. However, once approved, these treatments are often used differently than as tested in trials. We performed an analysis to determine the patterns of use of erythropoiesis-stimulating agents (ESAs). Methods We used the Surveillance, Epidemiology, and End Results-Medicare database to identify patients age 65 years or older with breast, lung, or colon cancer diagnosed between 1995 and 2005 who had one ESA and chemotherapy claim. Associations of patient, tumor, and physician-related factors with receipt of ESAs were analyzed. Results Of 21,091 patients analyzed, 5,099 (24.2%) received ESAs for 1 week or less (misuse), and 1,601 (7.6%) received ESAs for more than 14 weeks (prolonged use). Receipt of ESAs while not actively receiving chemotherapy (off label) occurred in 2,876 patients (13.6%). In a multivariable analysis, ESA misuse was associated with MD degree, female sex of physician, and earlier year of medical school graduation. Private practice physicians (odds ratio [OR], 0.78; 95% CI, 0.72 to 0.84) and high-volume physicians (OR, 0.78; 95% CI, 0.72 to 0.85) were less likely to use 1 week or less of ESA treatment. Treatment by high-volume oncologists (OR, 1.33; 95% CI, 1.14 to 1.55) and by oncologists who graduated from US medical schools (OR, 1.26; 95% CI, 1.12 to 1.42) predicted prolonged-duration ESA use, whereas female oncologists (OR, 0.79; 95% CI, 0.68 to 0.93) were less likely to prescribe prolonged ESA treatment. Private practice physicians (OR, 1.18; 95% CI, 1.02 to 1.38) and high-volume providers (OR, 1.58; 95% CI, 1.33 to 1.87) were more likely to prescribe more than 24 weeks of ESA treatment. Conclusion Our study demonstrated widespread variability in the use of ESAs. Physician characteristics exerted substantial influence on ESA use. Policies to discourage inappropriate use of cancer therapies are needed. J Clin Oncol 29:3408-3418. (C) 2011 by American Society of Clinical Oncology C1 [Malin, Jennifer; Hershman, Dawn L.] Columbia Univ, Med Ctr, New York, NY 10032 USA. [Malin, Jennifer] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Hershman, DL (reprint author), Columbia Univ, Med Ctr, 161 Ft Washington Ave,10-1068, New York, NY 10032 USA. EM dlh23@columbia.edu FU National Cancer Institute [R01CA134964] FX Supported in part by Grant No. R01CA134964 from the National Cancer Institute (D.L.H.). NR 38 TC 17 Z9 17 U1 1 U2 3 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 SEP 1 PY 2011 VL 29 IS 25 BP 3408 EP 3418 DI 10.1200/JCO.2010.34.5462 PG 11 WC Oncology SC Oncology GA 814EO UT WOS:000294429900019 PM 21810679 ER PT J AU Madison, KM Volpp, KG Halpern, SD AF Madison, Kristin M. Volpp, Kevin G. Halpern, Scott D. TI The Law, Policy, and Ethics of Employers' Use of Financial Incentives to Improve Health SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID WEIGHT-LOSS; REDUCTION; BEHAVIORS; UNDUE; SICK; RISK C1 [Madison, Kristin M.; Volpp, Kevin G.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn Wharton Sch, Dept Hlth Care Management, Philadelphia, PA USA. [Volpp, Kevin G.] Univ Penn Wharton Sch, Sch Med, Philadelphia, PA USA. [Volpp, Kevin G.; Halpern, Scott D.] Univ Penn, Leonard Davis Inst Ctr Hlth Incent, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Penn CMU Roybal Ctr Behav Econ & Hlth P30, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Halpern, Scott D.] Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. RP Madison, KM (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. NR 66 TC 23 Z9 23 U1 6 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD FAL PY 2011 VL 39 IS 3 BP 450 EP 468 DI 10.1111/j.1748-720X.2011.00614.x PG 19 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 810MI UT WOS:000294129000014 PM 21871042 ER PT J AU Goudreau, KA Ortman, MI Moore, JD Aldredge, L Helland, MK Fernandes, LA Gibson, S AF Goudreau, Kelly A. Ortman, Maria Idelsi Moore, Jean D. Aldredge, Lakshi Helland, Mary K. Fernandes, Laurie A. Gibson, Steve TI A Nurse Practitioner Residency Pilot Program A Journey of Learning SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article AB A collaborative team developed a yearlong residency experience for a staff nurse transitioning to a nurse practitioner role in the Veterans Affairs system. To assist others desiring to provide support, networking, and infrastructure to those transitioning into new roles, the authors discuss strengths and weaknesses of the pilot and lessons learned related to defining trainee versus resident, credentialing and privileging, and specific mentoring needed for the role of the nurse practitioner. C1 [Goudreau, Kelly A.; Moore, Jean D.] Portland VA Med Ctr, Nursing Primary Care Div, Portland, OR 97239 USA. [Fernandes, Laurie A.] Portland VA Med Ctr, Operat Care Div, Portland, OR 97239 USA. [Gibson, Steve] Portland VA Med Ctr, Clin Board Primary Care, Portland, OR 97239 USA. [Gibson, Steve] Portland VA Med Ctr, N Coast Clin, Portland, OR 97239 USA. [Gibson, Steve] Portland VA Med Ctr, Hillsboro Clin, Portland, OR 97239 USA. RP Goudreau, KA (reprint author), Portland VA Med Ctr, Nursing Primary Care Div, P2EDUC,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Kelly.Goudreau@va.gov NR 17 TC 5 Z9 5 U1 0 U2 3 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 SEP PY 2011 VL 41 IS 9 BP 382 EP 387 DI 10.1097/NNA.0b013e31822a7315 PG 6 WC Nursing SC Nursing GA 814OH UT WOS:000294465700010 PM 21881445 ER PT J AU Kimball, TA Barz, K Dimond, KR Edwards, JM Nehler, MR AF Kimball, Traci A. Barz, Ken Dimond, Kelly R. Edwards, James M. Nehler, Mark R. TI Efficiency of the kidney disease outcomes quality initiative guidelines for preemptive vascular access in an academic setting SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Western-Vascular-Society CY SEP 25-28, 2010 CL Sunriver, OR SP Western Vasc Soc ID RANDOMIZED CONTROLLED-TRIAL; PREOPERATIVE NONINVASIVE EVALUATION; ARTERIOVENOUS-FISTULA MATURATION; ABDOMINAL AORTIC-ANEURYSMS; 1ST-TIME DIALYSIS ACCESS; VEIN GRAFT FAILURE; HEMODIALYSIS ACCESS; AUTOLOGOUS FISTULAS; NATURAL-HISTORY; INCREASING USE AB Background: The National Kidney Foundation-Kidney Diseases Outcomes Quality Initiative (KDOQI) for vascular access guidelines state that patients with late-stage chronic kidney disease (CKD) should undergo native arteriovenous fistula (AVF) creation at least 6 months before anticipated start of hemodialysis (HD) treatments to obviate the need for other vascular access types, such as grafts or central catheters. Objective: The objective of this study was to determine the incidence of HD, the functional patency, and associated morbidity of AVFs in patients with late-stage CKD placed according to KDOQI. Methods: Consecutive patients with late-stage CKD who underwent AVF creation using KDOQI guidelines for anatomy between January 2003 and December 2007 at two tertiary academic centers were retrospectively evaluated. Baseline demographics, AVF type, and clinical comorbidities were recorded. Patients were stratified into one of four groups (groups A-D) over the follow-up course based on two end points: patency of their AVF and whether or not they began HD. The ideal primary outcome was AVF maturation and use for HD (group A; cumulative functional patency). Other outcomes included AVF patency but no HD (group B), HD with AVF failure (group C), or no HD and AVF abandonment (ie, death, refused hemodialysis, kidney transplant, or fistula failure; group D). Secondary outcomes were time to first cannulation, complications, and secondary interventions. Results: AVFs were created (46% forearm and 54% upper arm) in 150 patients with CKD (85% men, median age 63 years old). At a median follow-up of 10 months, 74 patients (49%) were receiving HD and of these, 48 patients (65%) were using their AVF (group A), whereas 26 patients (35%) were not due to fistula failure (group C). Thirty-four patients (23%) never initiated HD treatments, but had a viable AVF (group B), and 42 patients (28%) never initiated HD and abandoned their AVF (group D). Overall, AVE abandonment was 51%. Mean maturation time of all AVFs successfully cannulated was 285 days (range, 30-1265 days). Complications encountered were maturation failure for cannulation (15%), focal stenosis requiring intervention (13%), inadequate flows on FED (9%), steal syndrome (9%), and thrombosis (8%). Cumulative functional patency for all AVFs was 19% and 27% at 6 and 12 months, respectively, with a mean number of two interventions per AVF (range, 1-10). Mortality during the study was 23%. Conclusion: Despite successful creation and maturation of a preemptive AVF in nearly two-thirds of patients who started HD during the follow-up and given the following observations: the high overall mortality of the population, the morbidity and costs in secondary procedures of AVF creation, and the high incidence of abandonment, it is unclear if this strategy would demonstrate a benefit in a randomized trial when compared to other access strategies. (J Vase Surg 2011;54:760-6.) C1 [Kimball, Traci A.; Dimond, Kelly R.; Nehler, Mark R.] Univ Colorado, Vasc Surg Sect, Denver, CO 80202 USA. [Barz, Ken] Colorado Prevent Ctr, Denver, CO USA. [Edwards, James M.] Portland VA Med Ctr, Portland, OR USA. RP Nehler, MR (reprint author), Univ Colorado Denver, 12631 E 17th Ave,Room L15-5415, Aurora, CO 80045 USA. EM nehler@ucdenver.edu NR 29 TC 19 Z9 21 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2011 VL 54 IS 3 BP 760 EP 766 DI 10.1016/j.jvs.2011.03.006 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 815DC UT WOS:000294505300022 PM 21703804 ER PT J AU Grenon, SM Reilly, LM Ramaiah, VG AF Grenon, S. Marlene Reilly, Linda M. Ramaiah, Ventakesh G. TI Technical endovascular highlights for crossing the difficult aortic bifurcation SO JOURNAL OF VASCULAR SURGERY LA English DT Article AB Effective endovascular treatment requires successful vascular access to reach the targeted lesion. When the targeted lesion is infrainguinal in location, the vascular access options include the ipsilateral antegrade femoral approach, the contralateral retrograde femoral approach, or the transbrachial approach. The contralateral retrograde femoral route remains the most commonly used approach but may be challenging, particularly in the settings of a scarred groin or a difficult aortic bifurcation. The purpose of this article is to provide technical tips for the challenges encountered in obtaining contralateral femoral access for peripheral interventions with a difficult aortic bifurcation. (J Vasc Surg 2011;54:893-6.) C1 [Grenon, S. Marlene; Reilly, Linda M.] Univ Calif San Francisco, Div Vasc & Endovasc Surg, San Francisco, CA 94143 USA. [Grenon, S. Marlene; Reilly, Linda M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ramaiah, Ventakesh G.] Arizona Heart Inst, Phoenix, AZ USA. RP Grenon, SM (reprint author), Univ Calif San Francisco, Div Vasc & Endovasc Surg, San Francisco, CA 94143 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2011 VL 54 IS 3 BP 893 EP 896 DI 10.1016/j.jvs.2011.03.268 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 815DC UT WOS:000294505300045 PM 21664094 ER PT J AU Barnes, DE Yaffe, K AF Barnes, Deborah E. Yaffe, Kristine TI The projected effect of risk factor reduction on Alzheimer's disease prevalence SO LANCET NEUROLOGY LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; MILD COGNITIVE IMPAIRMENT; LATE-LIFE DEPRESSION; PHYSICAL-ACTIVITY; CARDIOVASCULAR-HEALTH; INCIDENT DEMENTIA; VASCULAR-DISEASE; BLOOD-PRESSURE; GLOBAL BURDEN; OLDER-ADULTS AB At present, about 33-9 million people worldwide have Alzheimer's disease (AD), and prevalence is expected to triple over the next 40 years. The aim of this Review was to summarise the evidence regarding seven potentially modifiable risk factors for AD: diabetes, midlife hypertension, midlife obesity, smoking, depression, cognitive inactivity or low educational attainment, and physical inactivity. Additionally, we projected the effect of risk factor reduction on AD prevalence by calculating population attributable risks (the percent of cases attributable to a given factor) and the number of AD cases that might be prevented by risk factor reductions of 10% and 25% worldwide and in the USA. Together, up to half of AD cases worldwide (17.2 million) and in the USA (2.9 million) are potentially attributable to these factors. A 10-25% reduction in all seven risk factors could potentially prevent as many as 1.1-3.0 million AD cases worldwide and 184000-492000 cases in the USA. C1 [Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Barnes, Deborah E.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement Sreet,151R, San Francisco, CA 94121 USA. EM deborah.barnes@ucsf.edu FU Alzheimer's Association; NARSAD; National Institute on Aging [K24 AG031155]; University of California, San Francisco, School of Medicine FX DEB is supported in part by the Alzheimer's Association, NARSAD, and the University of California, San Francisco, School of Medicine. KY is supported in part by the National Institute on Aging (K24 AG031155). NR 101 TC 598 Z9 611 U1 15 U2 156 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD SEP PY 2011 VL 10 IS 9 BP 819 EP 828 DI 10.1016/S1474-4422(11)70072-2 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 815NM UT WOS:000294532300010 PM 21775213 ER PT J AU Villeda, SA Luo, J Mosher, KI Zou, BD Britschgi, M Bieri, G Stan, TM Fainberg, N Ding, ZQ Eggel, A Lucin, KM Czirr, E Park, JS Couillard-Despres, S Aigner, L Li, G Peskind, ER Kaye, JA Quinn, JF Galasko, DR Xie, XMS Rando, TA Wyss-Coray, T AF Villeda, Saul A. Luo, Jian Mosher, Kira I. Zou, Bende Britschgi, Markus Bieri, Gregor Stan, Trisha M. Fainberg, Nina Ding, Zhaoqing Eggel, Alexander Lucin, Kurt M. Czirr, Eva Park, Jeong-Soo Couillard-Despres, Sebastien Aigner, Ludwig Li, Ge Peskind, Elaine R. Kaye, Jeffrey A. Quinn, Joseph F. Galasko, Douglas R. Xie, Xinmin S. Rando, Thomas A. Wyss-Coray, Tony TI The ageing systemic milieu negatively regulates neurogenesis and cognitive function SO NATURE LA English DT Article ID ADULT HIPPOCAMPAL NEUROGENESIS; NEURAL STEM-CELLS; LONG-TERM POTENTIATION; PROGENITOR CELLS; SELF-RENEWAL; AGED MICE; MEMORY; BRAIN; NEURONS; MODEL AB In the central nervous system, ageing results in a precipitous decline in adult neural stem/progenitor cells and neurogenesis, with concomitant impairments in cognitive functions(1). Interestingly, such impairments can be ameliorated through systemic perturbations such as exercise(1). Here, using heterochronic parabiosis we show that blood-borne factors present in the systemic milieu can inhibit or promote adult neurogenesis in an age-dependent fashion in mice. Accordingly, exposing a young mouse to an old systemic environment or to plasma from old mice decreased synaptic plasticity, and impaired contextual fear conditioning and spatial learning and memory. We identify chemokines-including CCL11 (also known as eotaxin)-the plasma levels of which correlate with reduced neurogenesis in heterochronic parabionts and aged mice, and the levels of which are increased in the plasma and cerebrospinal fluid of healthy ageing humans. Lastly, increasing peripheral CCL11 chemokine levels in vivo in young mice decreased adult neurogenesis and impaired learning and memory. Together our data indicate that the decline in neurogenesis and cognitive impairments observed during ageing can be in part attributed to changes in blood-borne factors. C1 [Villeda, Saul A.; Luo, Jian; Mosher, Kira I.; Britschgi, Markus; Bieri, Gregor; Stan, Trisha M.; Fainberg, Nina; Ding, Zhaoqing; Eggel, Alexander; Lucin, Kurt M.; Czirr, Eva; Park, Jeong-Soo; Rando, Thomas A.; Wyss-Coray, Tony] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Villeda, Saul A.; Mosher, Kira I.; Wyss-Coray, Tony] Stanford Univ, Sch Med, Neurosci IDP Program, Stanford, CA 94305 USA. [Zou, Bende; Xie, Xinmin S.] AfaSci Res Lab, Redwood City, CA 94063 USA. [Bieri, Gregor] Ecole Polytech Fed Lausanne, Swiss Fed Inst Technol, Sch Life Sci, CH-1015 Lausanne, Switzerland. [Stan, Trisha M.; Ding, Zhaoqing; Wyss-Coray, Tony] Stanford Univ, Sch Med, Immunol IDP Program, Stanford, CA 94305 USA. [Couillard-Despres, Sebastien; Aigner, Ludwig] Paracelsus Med Univ, Inst Mol Regenerat Med, A-5020 Salzburg, Austria. [Li, Ge; Peskind, Elaine R.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. [Peskind, Elaine R.] Vet Affairs NW Network Mental Illness Res Educ &, Seattle, WA 98108 USA. [Kaye, Jeffrey A.; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97201 USA. [Kaye, Jeffrey A.; Quinn, Joseph F.] Portland VA Med Ctr, Portland, OR 97207 USA. [Galasko, Douglas R.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Rando, Thomas A.; Wyss-Coray, Tony] VA Palo Alto Hlth Care Syst, Ctr Tissue Regenerat Repair & Restorat, Palo Alto, CA 94304 USA. [Rando, Thomas A.] Stanford Univ, Sch Med, Glenn Labs Biol Aging, Stanford, CA 94305 USA. RP Wyss-Coray, T (reprint author), Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. EM twc@stanford.edu RI Luo, Jian/B-8449-2014 OI Luo, Jian/0000-0002-2064-8467; Eggel, Alexander/0000-0001-8746-3339; Kaye, Jeffrey/0000-0002-9971-3478 FU Department of Veterans Affairs; National Institutes of Health Institute on Aging [R01 AG027505, P30AG08017]; California Initiative for Regenerative Medicine; National Institutes of Health [R01 MH078194]; Larry L. Hillblom Foundation [2008-A-023-FEL]; Feodor-Lynen postdoctoral fellowship; Swiss National Science Foundation; National Science Foundation; Kirschstein NRSA [AG034045-01, 1 F31 NS066676-01A1] FX We thank A. Brunet for critically reading the manuscript; M. Buckwalter for parabiosis instruction; T.-T. Huang for irradiation instruction; R. Corniola and C. Clelland for behavioural advice, S. Bauer Huang, H. Johns, J. Sun, H. Hefner, H. Alabsi and I. Villeda for technical assistance. This work was supported by grants from Anonymous (T.W.-C.), Department of Veterans Affairs (T.W.-C.), National Institutes of Health Institute on Aging (R01 AG027505, T.W.-C.), a California Initiative for Regenerative Medicine Award (T.W.-C.), National Institutes of Health (R01 MH078194, X.S.X.), National Institutes of Health Institute on Aging (P30AG08017, J.A.K.), a National Institutes of Health Director's Pioneer Award (T.A.R.), a Larry L. Hillblom Foundation postdoctoral fellowship (K.M.L.; 2008-A-023-FEL), a Feodor-Lynen postdoctoral fellowship (E.C.), a Swiss National Science Foundation postdoctoral fellowship (A.E.), a National Science Foundation predoctoral fellowship (S.A.V.; K.I.M.; T.M.S.), and Kirschstein NRSA predoctoral fellowships (1 F31 AG034045-01, S.A.V.; 1 F31 NS066676-01A1, Z.D.). NR 32 TC 457 Z9 471 U1 16 U2 130 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 1 PY 2011 VL 477 IS 7362 BP 90 EP U157 DI 10.1038/nature10357 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 813XT UT WOS:000294404300037 PM 21886162 ER PT J AU Salinsky, M Spencer, D Boudreau, E Ferguson, F AF Salinsky, Martin Spencer, David Boudreau, Eilis Ferguson, Felicia TI Psychogenic nonepileptic seizures in US veterans SO NEUROLOGY LA English DT Article ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; VIDEO-EEG; EPILEPSY; DIAGNOSIS; ATTACKS; IRAQ AB Objectives: Psychogenic nonepileptic seizures (PNES) are frequently encountered in epilepsy monitoring units (EMU) and can result in significant long-term disability. We reviewed our experience with veterans undergoing seizure evaluation in the EMU to determine the time delay to diagnosis of PNES, the frequency of PNES, and cumulative antiepileptic drug (AED) treatment. We compared veterans with PNES to civilians with PNES studied in the same EMU. Methods: We reviewed records of all patients admitted to one Veterans Affairs Medical Center (VAMC) EMU over a 10-year interval. These patients included 203 veterans and 726 civilians from the university affiliate. The percentage of patients with PNES was calculated for the veteran and civilian groups. Fifty veterans with only PNES were identified. Each veteran with PNES was matched to the next civilian patient with PNES. The 2 groups were compared for interval from onset of the habitual spells to EMU diagnosis, cumulative AED treatment, and other measures. Results: PNES were identified in 25% of veterans and 26% of civilians admitted to the EMU. The delay from onset of spells to EMU diagnosis averaged 60.5 months for veterans and 12.5 months for civilians (p < 0.001). Cumulative AED treatment was 4 times greater for veterans with PNES as compared to civilians (p < 0.01). Fifty-eight percent of veterans with PNES were thought to have seizures related to traumatic brain injury. Conclusions: The results indicate a substantial delay in the diagnosis of PNES in veterans as compared to civilians. The delay is associated with greater cumulative AED treatment. Neurology (R) 2011;77:945-950 C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Salinsky, M (reprint author), 3181 SW Sam Jackson Pk Rd,CR-120, Portland, OR 97239 USA. EM Salinsky@ohsu.edu FU NIH (NIDA, NIAAA) FX Dr. Salinsky serves on speakers' bureaus for UCB and Pfizer Inc and has served on scientific advisory boards for and received honoraria from Medtronic, Inc., Cyberonics Inc., and Lundbeck Inc. Dr. Spencer has served on the speakers' bureau of and received honoraria from UCB; serves as Patient Page Editor for Neurology (R), Chief Editor for EMedicine, Associate Editor for the Journal of Behavior and Brain Science, and on the Professional Advisory Board for Neurology Now; has received research support from NeuroPace, Inc.; and holds stock in StemCells, Inc. Dr. Boudreau serves on the editorial board of Aviation, Space, and Environmental Medicine; and has received research support from the NIH (NIDA, NIAAA). Dr. Ferguson reports no disclosures. NR 28 TC 29 Z9 29 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 2011 VL 77 IS 10 BP 945 EP 950 DI 10.1212/WNL.0b013e31822cfc46 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 815PR UT WOS:000294538100011 PM 21893668 ER PT J AU DePoortere, D Kofonow, JM Chen, B Chiu, AG Cohen, NA AF DePoortere, David Kofonow, Jennifer M. Chen, Bei Chiu, Alexander G. Cohen, Noam A. TI Murine Ciliotoxicity and Rabbit Sinus Mucosal Healing by Polyhydrated Ionogen SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation-and- OTO-EXPO CY SEP 25-29, 2010 CL Boston, MA SP Amer Acad Otolaryngol Head & Neck Surg Fdn, UMDNJ-New Jersey Med Sch DE mucosal wound healing; polyhydrated ionogen; inflammation; cytokines; matrix metalloproteases; ciliotoxicity ID CILIARY BEAT FREQUENCY; SURFACE RESPIRATORY EPITHELIUM; WOUND REPAIR; MUCOCILIARY TRANSPORT; MAXILLARY SINUS; ANIMAL-MODEL; SURGERY; NASAL; INTERFACE; EFFICACY AB Objectives. Determine the toxicity and efficacy of a novel antiprotease topical irrigation, polyhydrated ionogen (PHI) +/- MgBr(2), in improving sinonasal remucosalization following surgery. Study Design. Blinded, randomized controlled study. Setting. Academic. Subjects and Methods. Ciliary beat frequency (CBF) of murine nasal septal explants was continuously recorded before and after addition of PHI solution to asses for ciliotoxicity. To evaluate for efficacy in remucosalization, 9 New Zealand white rabbits underwent bilateral medial-wall maxillary mucosal stripping followed by placement of an indwelling irrigation catheter. In a randomized fashion one side received 3 mL of normal saline (NS) daily, whereas the contralateral side received PHI +/- MgBr(2). Following a 14-day therapeutic trial, remucosalization was assessed by hematoxylin and eosin staining and immunohistochemistry for beta-tubulin, a marker of cilia. A semiquantitative grading of ciliated remucosalization was applied with a chi-square test to compare the saline with the PHI +/- MgBr(2) treatment. Results. Safety evaluation of the PHI solutions demonstrated no evidence of ciliotoxicity. Histologic semiquantitative analysis of maxillary sinus remucosalization demonstrated significantly more ciliated epithelium (> 60%) in the majority of PHI (n = 4) and PHI with MgBr(2) (n = 5) treatment compared with the saline treatment (< 30%) (n = 9). This was confirmed with immunohistochemical staining for type IV beta-tubulin a marker of respiratory cilia. Conclusions. Success of functional endoscopic sinus surgery depends on restoration of normal mucociliary clearance. Topical PHI application has previously been demonstrated to significantly increase dermal wound healing. PHI solution is not ciliotoxic, and daily topical PHI or PHI MgBr(2) irrigation enhances ciliated remucosalization compared with saline. C1 [DePoortere, David; Kofonow, Jennifer M.; Chen, Bei; Chiu, Alexander G.; Cohen, Noam A.] Univ Penn, Sch Med, Dept Otorhinolaryngol, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia VA Med Ctr, Dept Otorhinolaryngol, Philadelphia, PA USA. RP Cohen, NA (reprint author), Ravdin Bldg,5th Floor, Philadelphia, PA 19104 USA. EM cohenn@uphs.upenn.edu RI Chiu, Alexander/J-1230-2014 OI Chiu, Alexander/0000-0002-7592-6575; Cohen, Noam/0000-0002-9462-3932 NR 30 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2011 VL 145 IS 3 BP 482 EP 488 DI 10.1177/0194599811399558 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 814OY UT WOS:000294467700022 PM 21493328 ER PT J AU Li, HK Esquivel, A Hubbard, LD Florez-Arango, JF Danis, RP Krupinski, EA AF Li, Helen K. Esquivel, Adol Hubbard, Larry D. Florez-Arango, Jose F. Danis, Ronald P. Krupinski, Elizabeth A. TI MOSAICS VERSUS EARLY TREATMENT DIABETIC RETINOPATHY SEVEN STANDARD FIELDS FOR EVALUATION OF DIABETIC RETINOPATHY SEVERITY SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE classification; diabetic retinopathy; digital; film; fundus photography; mosaic wide angle; seven standard fields; reproducibility; telemedicine ID FUNDUS PHOTOGRAPHY; RETINAL IMAGES; FOLLOW-UP; GLAUCOMA; SYSTEM; TELEOPHTHALMOLOGY; EPIDEMIOLOGY; TELEMEDICINE; POPULATION; RISK AB Purpose: To compare agreement between mosaicked and seven field photographs for classification of the diabetic retinopathy (DR) severity. Methods: Mosaic digital (MosD) images were compared with seven field stereo film (7FF) and stereo digital (7FD) photographs from a 152-eye cohort with full-spectrum Early Treatment of Diabetic Retinopathy severity levels for agreement on severity level, DR presence with ascending severity thresholds, DR index lesion presence, and classification repeatability. Results: There was a substantial agreement classifying the Early Treatment Diabetic Retinopathy Study DR severity level between MosD and 7FF (k(unweighted) = 0.59, k(linear weighted) = 0.83), MosD and 7FD (kappa = 0.62, kappa (weighted) = 0.86), and 7FD and 7FF (kappa = 0.62, kappa (weighted) = 0.86) images. Marginal homogeneity analyses found no significant difference between MosD and 7FF (P = 0.44, Bhapkar's test). Kappa between MosD and 7FF ranged from 0.75 to 0.91 for the presence or absence of DR at 8 ascending severity thresholds. Repeatability among readers using MosD images was similar to repeatability among those using 7FF or 7FD. Repeatability among readers using MosD and 7FF images at various severity thresholds was similar. Kappa between MosD and 7FF grading for identifying DR lesions ranged from 0.61 to 1.00. Conclusion: Mosaic images are generally comparable with standard seven-field photographs for classifying DR severity. RETINA 31:1553-1563, 2011 C1 [Li, Helen K.] Thomas Jefferson Univ, Dept Ophthalmol, Philadelphia, PA 19107 USA. [Florez-Arango, Jose F.] Univ Texas Hlth Sci Ctr, Sch Biomed Sci, Houston, TX USA. [Esquivel, Adol] Houston Vet Affairs Med Ctr, Houston, TX USA. [Esquivel, Adol] Baylor Coll Med, Houston, TX 77030 USA. [Hubbard, Larry D.; Danis, Ronald P.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Florez-Arango, Jose F.] Univ De Antioquia, Medellin, Colombia. [Krupinski, Elizabeth A.] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. RP Li, HK (reprint author), 1400 Hermann Dr, Houston, TX 77004 USA. EM hlimed@mac.com OI Florez-Arango, Jose F/0000-0001-9083-0195 FU Juvenile Diabetes Foundation Research International, New York, NY; Research to Prevent Blindness (Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch); Research to Prevent Blindness (Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health FX This study was supported by a grant from Juvenile Diabetes Foundation Research International, New York, NY (HKL) and by unrestricted grants from the Research to Prevent Blindness (Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch and the Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health). NR 34 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD SEP PY 2011 VL 31 IS 8 BP 1553 EP 1563 DI 10.1097/IAE.0b013e3182084273 PG 11 WC Ophthalmology SC Ophthalmology GA 814LS UT WOS:000294456100014 PM 21522039 ER PT J AU Ren, XF Akiyoshi, K Vandenbark, AA Hurn, PD Offner, H AF Ren, Xuefang Akiyoshi, Kozaburo Vandenbark, Arthur A. Hurn, Patricia D. Offner, Halina TI Programmed Death-1 Pathway Limits Central Nervous System Inflammation and Neurologic Deficits in Murine Experimental Stroke SO STROKE LA English DT Article DE coinhibitory pathway; inflammatory cells; MCAO; programmed death-1 ID REGULATORY T-CELLS; PD-1; AUTOIMMUNITY; ACTIVATION; EXPRESSION; INFECTION; RESPONSES; CNS; MACROPHAGES; LIGANDS AB Background and Purpose-Evaluation of infarct volumes and infiltrating immune cell populations in mice after middle cerebral artery occlusion strongly implicates a mixture of both pathogenic and regulatory immune cell subsets that affect stroke outcome. Our goal was to evaluate the contribution of the well-described coinhibitory pathway, programmed death (PD)-1, to the development of middle cerebral artery occlusion. Methods-Infarct volumes, functional outcomes, and effects on infiltrating immune cell populations were compared in wild-type C57BL/6 versus PD-1-deficient mice after 60 minutes middle cerebral artery occlusion and 96 hours reperfusion. Results-The results clearly demonstrate a previously unrecognized activity of the PD-1 pathway to limit infarct volume, recruitment of inflammatory cells from the periphery, activation of macrophages and central nervous system microglia, and functional neurological deficits. These regulatory functions were associated with increased percentages of circulating PD-ligand-1 and PD-ligand-2 expressing CD19(+) B-cells in blood, the spleen, and central nervous system with the capacity to inhibit activation of inflammatory T-cells and central nervous system macrophages and microglial cells through upregulated PD-1. Conclusions-Our novel observations are the first to implicate PD-1 signaling as a major protective pathway for limiting central nervous system inflammation in middle cerebral artery occlusion. This inhibitory circuit would likely be pivotal in reducing stroke-associated Toll-like receptor-2- and Toll like receptor-4-mediated release of neurotoxic factors by activated central nervous system microglia. (Stroke. 2011;42:2578-2583.) C1 [Ren, Xuefang; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, R&D 31, Portland, OR 97239 USA. [Ren, Xuefang; Akiyoshi, Kozaburo; Hurn, Patricia D.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, R&D 31, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU National Institutes of Health [NR03521, NS49210]; Biomedical Laboratory R&D Service, Department of Veterans Affairs FX This work was supported by National Institutes of Health grants NR03521 and NS49210 and the Biomedical Laboratory R&D Service, Department of Veterans Affairs. NR 33 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2011 VL 42 IS 9 BP 2578 EP U329 DI 10.1161/STROKEAHA.111.613182 PG 12 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 813BX UT WOS:000294342800046 PM 21737801 ER PT J AU Wagner, TH Lo, AC Peduzzi, P Bravata, DM Huang, GD Krebs, HI Ringer, RJ Federman, DG Richards, LG Haselkorn, JK Wittenberg, GF Volpe, BT Bever, CT Duncan, PW Siroka, A Guarino, PD AF Wagner, Todd H. Lo, Albert C. Peduzzi, Peter Bravata, Dawn M. Huang, Grant D. Krebs, Hermano I. Ringer, Robert J. Federman, Daniel G. Richards, Lorie G. Haselkorn, Jodie K. Wittenberg, George F. Volpe, Bruce T. Bever, Christopher T. Duncan, Pamela W. Siroka, Andrew Guarino, Peter D. TI An Economic Analysis of Robot-Assisted Therapy for Long-Term Upper-Limb Impairment After Stroke SO STROKE LA English DT Article DE cost; economic; rehabilitation; robotics; stroke ID AVERAGE COST; REHABILITATION; VA; HEALTH; STAYS AB Background and Purpose-Stroke is a leading cause of disability. Rehabilitation robotics have been developed to aid in recovery after a stroke. This study determined the additional cost of robot-assisted therapy and tested its cost-effectiveness. Methods-We estimated the intervention costs and tracked participants' healthcare costs. We collected quality of life using the Stroke Impact Scale and the Health Utilities Index. We analyzed the cost data at 36 weeks postrandomization using multivariate regression models controlling for site, presence of a prior stroke, and Veterans Affairs costs in the year before randomization. Results-A total of 127 participants were randomized to usual care plus robot therapy (n = 49), usual care plus intensive comparison therapy (n = 50), or usual care alone (n = 28). The average cost of delivering robot therapy and intensive comparison therapy was $5152 and $7382, respectively (P<0.001), and both were significantly more expensive than usual care alone (no additional intervention costs). At 36 weeks postrandomization, the total costs were comparable for the 3 groups ($17 831 for robot therapy, $19 746 for intensive comparison therapy, and $19 098 for usual care). Changes in quality of life were modest and not statistically different. Conclusions-The added cost of delivering robot or intensive comparison therapy was recuperated by lower healthcare use costs compared with those in the usual care group. However, uncertainty remains about the cost-effectiveness of robotic-assisted rehabilitation compared with traditional rehabilitation. Clinical Trial Registration-URL: http://clinicaltrials.gov. Unique identifier: NCT00372411. (Stroke. 2011;42:2630-2632.) C1 [Wagner, Todd H.] Stanford Univ, VA Palo Alto Hlth Econ Resource Ctr, Menlo Pk, CA 94025 USA. [Wagner, Todd H.] Stanford Univ, Dept Hlth Res & Policy, Menlo Pk, CA 94025 USA. [Lo, Albert C.] Brown Univ, Providence Vet Adm Med Ctr, Neurol Sect, Providence, RI 02912 USA. Brown Univ, Dept Neurol, Providence, RI 02912 USA. Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. Brown Univ, Dept Engn, Providence, RI 02912 USA. [Peduzzi, Peter] Yale Univ, Sch Publ Hlth, Vet Adm Connecticut Cooperat Studies Program Coor, New Haven, CT USA. [Bravata, Dawn M.] Indianapolis Vet Adm Med Ctr, Indianapolis, IN USA. [Bravata, Dawn M.] Indiana Univ Sch Med, Indianapolis, IN USA. [Huang, Grant D.] Vet Affairs Off Res & Dev, Cooperat Studies Program Cent Off, Washington, DC USA. [Krebs, Hermano I.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Ringer, Robert J.] Univ New Mexico, Vet Affairs Cooperat Studies Program Clin Res Pha, Albuquerque, NM 87131 USA. [Federman, Daniel G.] Vet Affairs Connecticut Healthcare Syst, Dept Med, West Haven, CT USA. Yale Univ, Sch Med, New Haven, CT USA. [Richards, Lorie G.] Univ Florida, N Florida S Georgia Vet Hlth Syst, Gainesville, FL USA. [Richards, Lorie G.] Univ Florida, Occupat Therapy Dept, Gainesville, FL USA. [Haselkorn, Jodie K.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Wittenberg, George F.] Univ Maryland, Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA. [Volpe, Bruce T.] Cornell Univ, Dept Neurol & Neurosci, Weill Med Coll, White Plains, NY USA. [Bever, Christopher T.] Vet Affairs Maryland Hlth Care Syst, Neurol Serv, Baltimore, MD USA. [Bever, Christopher T.] Vet Affairs Maryland Hlth Care Syst, Res Serv, Baltimore, MD USA. Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Phys Therapy, Baltimore, MD 21201 USA. [Duncan, Pamela W.] Duke Univ, Dept Community & Family Med, Durham, NC USA. [Siroka, Andrew] Vet Affairs Palo Alto Hlth Econ Resource Ctr, Palo Alto, CA USA. [Guarino, Peter D.] Cooperat Studies Coordinating Ctr, West Haven, CT USA. RP Wagner, TH (reprint author), Stanford Univ, VA Palo Alto Hlth Econ Resource Ctr, 795 Willow Rd,152 MPD, Menlo Pk, CA 94025 USA. EM Todd.Wagner@va.gov OI Volpe, Bruce/0000-0002-1098-1848 FU Department of Veterans Affairs; Rehabilitation Research and Development Service FX This study was funded by the Department of Veterans Affairs Cooperative Studies Program and the Rehabilitation Research and Development Service. NR 24 TC 39 Z9 44 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2011 VL 42 IS 9 BP 2630 EP U422 DI 10.1161/STROKEAHA.110.606442 PG 20 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 813BX UT WOS:000294342800056 PM 21757677 ER PT J AU Huddle, TS AF Huddle, Thomas S. TI Do Medical Professionalism and Medical Education Involve Commitments to Political Advocacy? Reply SO ACADEMIC MEDICINE LA English DT Letter C1 [Huddle, Thomas S.] Univ Alabama, Dept Med, Div Gen Internal Med, Med Sch Birmingham, Birmingham, AL 35294 USA. [Huddle, Thomas S.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Huddle, TS (reprint author), Univ Alabama, Dept Med, Div Gen Internal Med, Med Sch Birmingham, Birmingham, AL 35294 USA. EM thuddle@uab.edu RI liu, jing/D-9482-2012 NR 0 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 2011 VL 86 IS 9 BP 1065 EP 1065 DI 10.1097/ACM.0b013e3182277361 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 811YH UT WOS:000294254300010 ER PT J AU Becher, A El-Serag, H AF Becher, A. El-Serag, H. TI Systematic review: the association between symptomatic response to proton pump inhibitors and health-related quality of life in patients with gastro-oesophageal reflux disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Review ID MAINTENANCE TREATMENT; PRIMARY-CARE; ESOMEPRAZOLE; RABEPRAZOLE; HEARTBURN; GERD AB Background Some patients with gastro-oesophageal reflux disease (GERD) experience persistent reflux symptoms on proton pump inhibitor (PPI) therapy. The relationship between persistent reflux symptoms and health-related quality of life (HRQoL) is unclear. Aim To assess the relationship between persistent reflux symptoms on PPI therapy and HRQoL in patients with GERD. Methods Systematic searches were conducted in PubMed and Embase. Eligible studies had to have used psychometrically evaluated patient reported outcome instruments to assess HRQoL. Results Nine studies were included; supplementary data were obtained for four of these. The effect of persistent reflux symptoms despite PPI therapy on physical HRQoL was assessed in seven studies and that on mental HRQoL in five studies. Compared with patients whose reflux symptoms responded to PPIs, those with persistent symptoms had, on average, 8-16% lower scores for physical health (five studies) and 2-12% lower scores for mental health (three studies). Three studies included data on the effect of baseline HRQoL on subsequent symptomatic response to PPI therapy. Patients with persistent symptoms had clinically relevant lower psychological well-being at baseline compared with those whose symptoms responded to PPIs (average score difference: 7%; two studies). High anxiety levels at baseline seemed to be an important aspect of persistent symptoms. Conclusions Persistent reflux symptoms on PPI therapy are associated with reduced physical and mental HRQoL, while reduced mental HRQoL at baseline seems to impair symptomatic response to PPIs. HRQoL may need to be considered alongside reflux symptom frequency and severity when making decisions about disease management. C1 [Becher, A.] Oxford PharmaGenesis Ltd, Res Evaluat Unit, Oxford, England. [El-Serag, H.] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. [El-Serag, H.] Baylor Coll Med, Houston, TX 77030 USA. RP El-Serag, H (reprint author), Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu FU Bayer pharmaceuticals; Houston VA HSR&D Center of Excellence [HFP90-020]; AstraZeneca; AstraZeneca R&D, Molndal, Sweden FX Declaration of personal interests: Dr El-Serag has served as a consultant for Vertex, has received a grant from Bayer pharmaceuticals, and has received research funding from the Houston VA HSR&D Center of Excellence (HFP90-020). Dr Becher is a contracted employee of Oxford PharmaGenesis (TM) Ltd, which receives funding from AstraZeneca. Declaration of funding interests: Writing support was provided by Dr Lucy Bomphrey of Oxford PharmaGenesis (TM) Ltd and funded by AstraZeneca R&D, Molndal, Sweden. NR 22 TC 36 Z9 40 U1 0 U2 11 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 SEP PY 2011 VL 34 IS 6 BP 618 EP 627 DI 10.1111/j.1365-2036.2011.04774.x PG 10 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 810EE UT WOS:000294107400003 PM 21770991 ER PT J AU Mahlen, SD Clarridge, JE AF Mahlen, Steven D. Clarridge, Jill E., III TI Evaluation of a Selection Strategy Before Use of 16S rRNA Gene Sequencing for the Identification of Clinically Significant Gram-Negative Rods and Coccobacilli SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE 16S rRNA gene sequencing; Gram-negative rod; Bacteria selection for sequence identification ID BACTERIAL IDENTIFICATION; MICROBIOLOGY; CARD AB Although 16S ribosomal RNA (rRNA) gene sequencing is well established for correctly identifying bacteria, its most efficient use in a routine clinical laboratory is not clear. We devised and evaluated a strategy to select gram-negative rods and coccobacilli (GNRCB) for which sequencing might be necessary before routine identification methods had been exhausted. The prospectively applied selection criteria were primarily based on the isolate's display of unusual or discordant phenotypic results and/or disease correlation. By using this strategy, we selected a total of 120 GNRCB (representing only similar to 2% of all identified). The strategy was demonstrated to be efficient because the preliminary phenotypic identification for 79.2% of those isolates needed revision (18.2% were novel and about a third would have required further extensive testing). The knowledge that 1.6% (ie, 79% of 2%) of isolated GNRCB might benefit from sequence identification could provide guidelines for routine clinical laboratories toward efficient use of sequence analysis. C1 [Mahlen, Steven D.; Clarridge, Jill E., III] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Clarridge, Jill E., III] Vet Affairs Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, Seattle, WA USA. RP Clarridge, JE (reprint author), VA PSHCS, Pathol & Lab Med Serv 113, 1660 S Columbian Way, Seattle, WA 98108 USA. FU VA Puget Sound Health Care System FX This material is the result of work supported by resources from the VA Puget Sound Health Care System. NR 16 TC 6 Z9 7 U1 0 U2 4 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2011 VL 136 IS 3 BP 381 EP 388 DI 10.1309/AJCP61CGNXCXVSPR PG 8 WC Pathology SC Pathology GA 809SA UT WOS:000294075800006 PM 21846913 ER PT J AU Korte, JE Magruder, KM Chiuzan, CC Logan, SL Killeen, T Bandyopadhyay, D Brady, KT AF Korte, Jeffrey E. Magruder, Kathryn M. Chiuzan, Codruta C. Logan, Sarah L. Killeen, Therese Bandyopadhyay, Dipankar Brady, Kathleen T. TI Assessing Drug Use during Follow-Up: Direct Comparison of Candidate Outcome Definitions in Pooled Analyses of Addiction Treatment Studies SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE drug addiction; measurement; clinical trials; methodology ID ABUSE TREATMENT PROGRAMS; SELF-REPORT; ALCOHOL DEPENDENCE; CLINICAL-TRIALS; CONCORDANCE; REDUCTION; DRINKING AB Background: Selection of appropriate outcome measures is important for clinical studies of drug addiction treatment. Researchers use various methods for collecting drug use outcomes and must consider substances to be included in a urine drug screen (UDS); accuracy of self-report; use of various instruments and procedures for collecting self-reported drug use; and timing of outcome assessments. Objectives: We sought to define a set of candidate measures to (1) assess their intercorrelation and (2) identify any differences in results. Methods: Data were combined from completed protocols in the National Institute on Drug Abuse Clinical Trials Network (CTN), with a total of 1897 participants. We defined nine outcome measures based on UDS, self-report, or a combination. Multivariable, multilevel generalized estimating equation models were used to assess subgroup differences in intervention success, controlling for baseline differences and accounting for clustering by CTN protocols. Results: There were high correlations among all candidate outcomes. All outcomes showed consistent overall results with no significant intervention impact on drug use during follow-up. However, with most UDS variables, but not with self-report or "corrected self-report," we observed a significant gender-ethnicity interaction with benefit shown in African American women, White women, and Hispanic men. Conclusion: Despite strong associations between candidate measures, we found some important differences in results. Scientific Significance: In this study, we demonstrated the potential utility and impact of combining UDS and self-report data for drug use assessment. Our results suggest possible differences in intervention efficacy by gender and ethnicity, but highlight the need to cautiously interpret observed interactions. C1 [Korte, Jeffrey E.; Magruder, Kathryn M.; Chiuzan, Codruta C.; Logan, Sarah L.; Bandyopadhyay, Dipankar] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Magruder, Kathryn M.; Brady, Kathleen T.] Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Magruder, Kathryn M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Div Behav Epidemiol & Community Hlth, Charleston, SC 29425 USA. [Killeen, Therese; Brady, Kathleen T.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Div Clin Neurosci, Charleston, SC 29425 USA. RP Korte, JE (reprint author), Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, 135 Cannon St,Suite 303, Charleston, SC 29425 USA. EM korte@musc.edu FU NIDA NIH HHS [5 U10 DA013727, U10 DA013727, U10 DA013727-11, U10 DA013727-10S1] NR 11 TC 3 Z9 3 U1 0 U2 5 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 SEP PY 2011 VL 37 IS 5 BP 358 EP 366 DI 10.3109/00952990.2011.602997 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 810HN UT WOS:000294116500012 PM 21854278 ER PT J AU Ittiwut, R Listman, JB Ittiwut, C Cubells, JF Weiss, RD Brady, K Oslin, D Farrer, LA Kranzler, HR Gelernter, J AF Ittiwut, Rungnapa Listman, Jennifer B. Ittiwut, Chupong Cubells, Joseph F. Weiss, Roger D. Brady, Kathleen Oslin, David Farrer, Lindsay A. Kranzler, Henry R. Gelernter, Joel TI Association Between Polymorphisms in Catechol-O-methyltransferase (COMT) and Cocaine-Induced Paranoia in European-American and African-American Populations SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE COMT; cocaine-induced paranoia; family-based analysis; haplotype; SNP; positive selection ID 22Q11.2 DELETION SYNDROME; BETA-HYDROXYLASE ACTIVITY; GENOMEWIDE LINKAGE SCAN; HUMAN BRAIN; FUNCTIONAL POLYMORPHISM; GENETIC-VARIATION; MESSENGER-RNA; DBH LOCUS; HAPLOTYPE; DEPENDENCE AB Catechol-O-methyltransferase (genetic locus, COMT) is a major enzyme involved in catecholamine metabolism and has been associated with numerous psychiatric phenotypes. We studied COMT SNPs and haplotypes in cocaine-induced paranoia (CIP) in African-American (AA) and European-American (EA) populations. We genotyped 17 SNPs across the COMT locus in 319 AA pedigrees (848 individuals) and 302 EA pedigrees (707 individuals). Family-controlled association analyses were conducted using FBAT. We found SNP rs737865 to be nominally significantly associated in the AA family population (P = 0.05). In EAs, the best-known marker, rs4680 (Val158Met), was nominally significant in additive models (P = 0.03). SNP rs174696 also showed nominal significance in additive models (P = 0.02). We considered the three SNPs (rs737866-rs4680-rs174696) together in haplotype analysis in both family populations, using HBAT. The A-A-T haplotype was significantly associated with CIP in EAs (Z = 2.845; P = 0.0044, global P = 0.020). We then studied COMT SNPs in an additional 738 AA and 404 EA unrelated cocaine dependent individuals with and without paranoia. The A-A-T haplotype was significantly associated to CIP in the AA unrelated population (P = 0.0015). Two haplotypes, A-G-C and A-A-C, were significant in the EA unrelated population (P = 0.001 and 0.0003). We also identified rs4680 and three other SNPs, rs933271, rs5993883, and rs740603, as potentially functional variants, as predicted by a signature of positive selection in unrelated EAs and AAs. Based on our robust family-controlled and unrelated-affected analyses, we conclude that COMT is associated with CIP, possibly as a result of its role in the metabolism of dopamine and norepinephrine. (C) 2011 Wiley-Liss, Inc. C1 [Gelernter, Joel] Yale Univ Sch Med, VAMC 116A2, Dept Psychiat, West Haven, CT 06516 USA. [Ittiwut, Rungnapa; Ittiwut, Chupong; Gelernter, Joel] VA Connecticut Healthcare Syst, West Haven, CT USA. [Ittiwut, Rungnapa] Minist Publ Hlth, Inst Pathol, Dept Med Serv, Bangkok, Thailand. [Ittiwut, Chupong] Chulalongkorn Univ, Fac Med, Chulalongkorn GenePRO Ctr, Bangkok 10330, Thailand. [Cubells, Joseph F.] Emory Univ Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Weiss, Roger D.] McLean Hosp, Belmont, MA 02178 USA. [Weiss, Roger D.] Harvard Univ, Sch Med, Boston, MA USA. [Brady, Kathleen] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Oslin, David] Univ Penn Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA USA. [Farrer, Lindsay A.] Boston Univ Sch Med, Dept Med Genet Neurol Ophthalmol Genet & Genom Ep, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ Sch Publ Hlth, Dept Med Genet Neurol Ophthalmol Genet & Genom Ep, Boston, MA USA. [Kranzler, Henry R.] Univ Connecticut Sch Med, Dept Psychiat & Genet & Dev Biol, Farmington, CT USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Gelernter, Joel] Dept Neurobiol, New Haven, CT USA. RP Gelernter, J (reprint author), Yale Univ Sch Med, VAMC 116A2, Dept Psychiat, 950 Campbell Ave, West Haven, CT 06516 USA. EM joel.gelernter@yale.edu OI Farrer, Lindsay/0000-0001-5533-4225 FU NIH (NIDA) [R01 DA12690, R01 DA12849, R01 AA0175350, R01 AA11330, D43 TW06166, K24 DA022288]; GCRC [M01 RR06192]; US Department of Veterans Affairs (the VA Connecticut-Massachusetts Mental Illness Research, Education and Clinical Center (MIRECC)); Merck; ACTIVE FX Grant sponsor: NIH (NIDA); Grant numbers: R01 DA12690, R01 DA12849, R01 AA0175350, R01 AA11330, D43 TW06166, K24 DA022288; Grant sponsor: GCRC; Grant number: M01 RR06192; Grant sponsor: US Department of Veterans Affairs (the VA Connecticut-Massachusetts Mental Illness Research, Education and Clinical Center (MIRECC)).; Dr. Kranzler has been a paid consultant for Alkermes, GlaxoSmithKline, and Gilead. He has received research support from Merck. He also reports associations with Eli Lilly, Janssen, Schering Plough, Lundbeck, Alkermes, GlaxoSmithKline, Abbott, and Johnson ACTIVE) and Dr. Kranzler receives support from ACTIVE. NR 38 TC 9 Z9 9 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP PY 2011 VL 156B IS 6 BP 651 EP 660 DI 10.1002/ajmg.b.31205 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 811QR UT WOS:000294228600003 PM 21656904 ER PT J AU Finney, JW Humphreys, K Kivlahan, DR Harris, AHS AF Finney, John W. Humphreys, Keith Kivlahan, Daniel R. Harris, Alex H. S. TI Why Health Care Process Performance Measures Can Have Different Relationships to Outcomes for Patients and Hospitals: Understanding the Ecological Fallacy SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID USE-DISORDER-TREATMENT; CLINICAL-OUTCOMES; CLUSTERED DATA; QUALITY-MEASURES; CONTINUING CARE; MULTILEVEL; BIAS; EXPERIENCE; MORTALITY; ROBINSON AB Relationships between health care process performance measures (PPMs) and outcomes can differ in magnitude and even direction for patients versus higher level units (e.g., health care facilities). Such discrepancies can arise because facility-level relationships ignore PPM outcome relationships for patients within facilities, may have different confounders than patient-level PPM outcome relationships, and may reflect facility effect modification of patient PPM outcome relationships. If a patient-level PPM is related to better patient outcomes, that care process should be encouraged. However, the finding in a multilevel analysis that the proportion of patients receiving PPM care across facilities nevertheless is linked to poor hospital outcomes would suggest that interventions targeting the health care facility also are needed. (Am J Public Health. 2011; 101:1635-1642. doi:10.2105/AJPH.2011.300153) C1 [Kivlahan, Daniel R.] Vet Affairs Puget Sound Hlth Care Syst, Subst Use Disorders Qual Enhancement Res Initiat, Seattle, WA USA. [Finney, John W.; Humphreys, Keith; Harris, Alex H. S.] Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA USA. RP Finney, JW (reprint author), VA Palo Alto Hlth Care Syst 152MPD, Ctr Hlth Care Evaluat, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM john.finney@va.gov FU Health Services Research and Development Service (HSRD); Office of Research and Development; US Department of Veterans Affairs [SUS 99-015, IIR-07-092-1]; HSR&D Substance Use Disorder Quality Enhancement Research Initiative FX Preparation of this article was supported by the Health Services Research and Development Service (HSR&D), Office of Research and Development, US Department of Veterans Affairs (grants SUS 99-015 and IIR-07-092-1), and by the HSR&D Substance Use Disorder Quality Enhancement Research Initiative. NR 48 TC 30 Z9 30 U1 1 U2 13 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2011 VL 101 IS 9 BP 1635 EP 1642 DI 10.2105/AJPH.2011.300153 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 809XR UT WOS:000294090500017 PM 21778493 ER PT J AU Modarresi, S Motamedi, D Jude, CM AF Modarresi, Shahla Motamedi, Daria Jude, Cecilia Matilda TI Superior Labral Anteroposterior Lesions of the Shoulder: Part 1, Anatomy and Anatomic Variants SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE glenoid labrum; MR arthrogram; MRI; overhead athletes; shoulder pain; SLAP; sports medicine; superior labral anteroposterior tear ID MR ARTHROGRAPHY; GLENOID LABRUM; SLAP LESIONS; BICIPITAL COMPLEX; ANTEROSUPERIOR LABRUM; SUBLABRAL RECESS; CT ARTHROGRAPHY; BUFORD COMPLEX; LONG HEAD; DIAGNOSIS AB OBJECTIVE. The objectives of this article are to provide a pictorial review of labral anatomy and physiology, with particular attention to commonly seen anatomic variants and pitfalls, and to present standard imaging techniques and approaches to MRI interpretation to facilitate diagnosis and treatment of superior labral anteroposterior (SLAP) lesions. CONCLUSION. Imaging plays an important role in the diagnosis of SLAP tears. Knowledge of glenolabral anatomy, related structures and variants, proper imaging techniques, and a systematic approach to MRI interpretation is important in the diagnosis and treatment planning of the 10 types of SLAP lesions. Arthroscopy offers a means for definitive diagnosis. C1 [Modarresi, Shahla] W Los Angeles VA Med Ctr, Dept Imaging, Musculoskeletal Sect, Los Angeles, CA 90073 USA. [Motamedi, Daria] Cedars Sinai Med Ctr, Dept Imaging, Los Angeles, CA 90048 USA. [Jude, Cecilia Matilda] Olive View UCLA Med Ctr, Dept Imaging, Sylmar, CA 91342 USA. RP Modarresi, S (reprint author), W Los Angeles VA Med Ctr, Dept Imaging, Musculoskeletal Sect, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM shahlamodarresi@yahoo.com NR 38 TC 11 Z9 13 U1 2 U2 6 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 SEP PY 2011 VL 197 IS 3 BP 596 EP 603 DI 10.2214/AJR.10.7236 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 810YD UT WOS:000294165600043 PM 21862801 ER PT J AU Modarresi, S Motamedi, D Jude, CM AF Modarresi, Shahla Motamedi, Daria Jude, Cecilia Matilda TI Superior Labral Anteroposterior Lesions of the Shoulder: Part 2, Mechanisms and Classification SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE glenoid labrum; MR arthrogram; MRI; overhead athletes; shoulder pain; SLAP; sports medicine; superior labral anteroposterior tear ID ANTERIOR-POSTERIOR LESIONS; II SLAP LESIONS; MR ARTHROGRAPHY; INTERNAL IMPINGEMENT; GLENOID LABRUM; DIAGNOSIS; REPAIR; VARIANTS; COMPLEX; TENDON AB OBJECTIVE. The objectives of this article are to discuss the 10 distinct patterns of superior labral anteroposterior (SLAP) tears to facilitate adequate diagnosis and treatment. Correlations with clinical presentation, mechanism of injury, and treatment will enhance understanding. CONCLUSION. Imaging plays an important role in the diagnosis of SLAP tears. Knowledge of glenolabral anatomy, related structures and variants, proper imaging techniques, and a systematic approach to MRI interpretation is important in the diagnosis and treatment planning of the 10 types of SLAP lesions. Arthroscopy offers a means for definitive diagnosis. C1 [Modarresi, Shahla] W Los Angeles VA Med Ctr, Dept Imaging, Musculoskeletal Sect, Los Angeles, CA 90073 USA. [Motamedi, Daria] Cedars Sinai Med Ctr, Dept Imaging, Los Angeles, CA 90048 USA. [Jude, Cecilia Matilda] Olive View UCLA Med Ctr, Dept Imaging, Sylmar, CA 91342 USA. RP Modarresi, S (reprint author), W Los Angeles VA Med Ctr, Dept Imaging, Musculoskeletal Sect, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM shahlamodarresi@yahoo.com NR 29 TC 11 Z9 12 U1 2 U2 10 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 SEP PY 2011 VL 197 IS 3 BP 604 EP 611 DI 10.2214/AJR.11.6575 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 810YD UT WOS:000294165600044 PM 21862802 ER PT J AU Neal, MD Alverdy, JC Hall, DE Simmons, RL Zuckerbraun, BS AF Neal, Matthew D. Alverdy, John C. Hall, Daniel E. Simmons, Richard L. Zuckerbraun, Brian S. TI Diverting Loop Ileostomy and Colonic Lavage An Alternative to Total Abdominal Colectomy for the Treatment of Severe, Complicated Clostridium difficile Associated Disease SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 131st Annual Meeting of the American-Surgical-Association CY APR 14-16, 2011 CL Boca Raton, FL SP Amer Surg Assoc ID PSEUDOMEMBRANOUS COLITIS; CO-MORBIDITY; PREDICTORS; MORTALITY; INFECTION; OUTBREAK; DIARRHEA; SURGERY; AMERICA; STRAIN AB Objective: To determine whether a minimally invasive, colon-preserving approach could serve as an alternative to total colectomy in the treatment of severe, complicated Clostridium difficile-associated disease (CDAD). Background: C. difficile is a significant cause of morbidity and mortality worldwide. Most cases will respond to antibiotic therapy, but 3% to 10% of patients progress to a severe, complicated, or "fulminant" state of life-threatening systemic toxicity. Although the advocated surgical treatment of total abdominal colectomy with end ileostomy improves survival in severe, complicated CDAD, outcomes remain poor with associated mortality rates ranging from 35% to 80%. Methods: All patients who were diagnosed with severe, complicated ("fulminant") CDAD and were treated at the University of Pittsburgh Medical Center or VA Pittsburgh Healthcare System between June 2009 and January 2011 were treated with this novel approach. The surgical approach involved creation of a loop ileostomy, intraoperative colonic lavage with warmed polyethylene glycol 3350/electrolyte solution via the ileostomy and postoperative antegrade instillation of vancomycin flushes via the ileostomy. The primary end point for the study was resolution of CDAD. The matching number of patients treated with colectomy for CDAD preceding the initiation of this current treatment strategy was analyzed for historical comparison. Results: Forty-two patients were treated during this time period. There was no significant difference in age, sex, pharmacologic immunosuppression, and Acute Physiology and Chronic Health Evaluation-II scores between our current cohort and historical controls. The operation was accomplished laparoscopically in 35 patients (83%). This treatment strategy resulted in reduced mortality compared to our historical population (19% vs 50%; odds ratio, 0.24; P = 0.006). Preservation of the colon was achieved in 39 of 42 patients (93%). Conclusions: Loop ileostomy and colonic lavage are an alternative to colectomy in the treatment of severe, complicated CDAD resulting in reduced morbidity and preservation of the colon. C1 [Neal, Matthew D.; Hall, Daniel E.; Simmons, Richard L.; Zuckerbraun, Brian S.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Alverdy, John C.] Univ Chicago, Chicago, IL 60637 USA. [Hall, Daniel E.; Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), NW653 MUH,3459 5th Ave, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu RI Hall, Daniel/H-4843-2013 OI Hall, Daniel/0000-0001-6382-0522 NR 31 TC 100 Z9 100 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 2011 VL 254 IS 3 BP 423 EP 429 DI 10.1097/SLA.0b013e31822ade48 PG 7 WC Surgery SC Surgery GA 811XQ UT WOS:000294252500003 PM 21865943 ER PT J AU Franklin, TR Wang, Z Sciortino, N Harper, D Li, Y Hakun, J Kildea, S Kampman, K Ehrman, R Detre, JA O'Brien, CP Childress, AR AF Franklin, Teresa R. Wang, Ze Sciortino, Nathan Harper, Derek Li, Yin Hakun, Jonathan Kildea, Susan Kampman, Kyle Ehrman, Ron Detre, John A. O'Brien, Charles P. Childress, Anna Rose TI Modulation of resting brain cerebral blood flow by the GABA B agonist, baclofen: A longitudinal perfusion fMRI study SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Baclofen; GABA B agonist; Resting baseline perfusion fMRI; Addiction; Limbic circuitry; Cerebral blood flow ID VENTRAL TEGMENTAL AREA; DUAL-PROBE MICRODIALYSIS; PLACEBO-CONTROLLED TRIAL; ORBITOFRONTAL CORTEX; CIGARETTE-SMOKING; MESOLIMBIC DOPAMINE; NICOTINE DEPENDENCE; PREFRONTAL CORTEX; LIMBIC ACTIVATION; BIPOLAR DISORDER AB Background: Preclinical studies confirm that the GABA B agonist, baclofen blocks dopamine release in the reward-responsive ventral striatum (VS) and medial prefrontal cortex, and consequently, blocks drug motivated behavior. Its mechanism in humans is unknown. Here, we used continuous arterial spin labeled (CASL) perfusion fMRI to examine baclofen's effects on blood flow in the human brain. Methods: Twenty-one subjects (all smokers, 12 females) were randomized to receive either baclofen (80 mg/day; N = 10) or placebo (N = 11). A five minute quantitative perfusion fMRI resting baseline (RB) scan was acquired at two time points; prior to the dosing regimen (Time 1) and on the last day of 21 days of drug administration (Time 2). SPM2 was employed to compare changes in RB from Time 1 to 2. Results: Baclofen diminished cerebral blood flow (CBF) in the VS and mOFC and increased it in the lateral OFC, a region involved in suppressing previously rewarded behavior. CBF in bilateral insula was also blunted by baclofen (T values ranged from -11.29 to 15.3 at p = 0.001, 20 contiguous voxels). CBF at Time 2 was unchanged in placebo subjects. There were no differences between groups in side effects or cigarettes smoked per day (at either time point). Conclusions: Baclofen's modulatory actions on regions involved in motivated behavior in humans are reflected in the resting state and provide insight into the underlying mechanism behind its potential to block drug-motivated behavior, in preclinical studies, and its putative effectiveness as an anti-craving/anti-relapse agent in humans. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Franklin, Teresa R.] Univ Penn, Dept Psychiat, Ctr Studies Addict, Philadelphia, PA 19104 USA. [Detre, John A.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Detre, John A.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Kampman, Kyle; Ehrman, Ron; O'Brien, Charles P.; Childress, Anna Rose] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Franklin, TR (reprint author), Univ Penn, Dept Psychiat, Ctr Studies Addict, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM franklin_t@mail.trc.upenn.edu RI Wang, Ze/A-1043-2007 FU NIH [DA015149, K01 DA 015426-011A1, 5-P60-DA-005186-18, NS045839, BCS-0224007, RR02305]; Alexander Foundation; GCRC of the University of Pennsylvania FX Work supported by NIH grants DA015149, K01 DA 015426-011A1, 5-P60-DA-005186-18, and NS045839, BCS-0224007, RR02305, The Alexander Foundation and the GCRC of the University of Pennsylvania NR 77 TC 19 Z9 19 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2011 VL 117 IS 2-3 BP 176 EP 183 DI 10.1016/j.drugalcdep.2011.01.015 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 811TZ UT WOS:000294240300013 PM 21333466 ER PT J AU Howard, TE Yanover, C Mahlangu, J Krause, A Viel, KR Kasper, CK Pratt, KP AF Howard, T. E. Yanover, C. Mahlangu, J. Krause, A. Viel, K. R. Kasper, C. K. Pratt, K. P. TI Haemophilia management: time to get personal? SO HAEMOPHILIA LA English DT Review DE antigen-presentation repertoire; factor VIII inhibitor; haemophilia A; HLA class II; non synonymous-SNPs; pharmacogenetics ID FACTOR-VIII GENE; RECOMBINANT FACTOR-VIII; PREVIOUSLY UNTREATED PATIENTS; T-CELL RESPONSES; INHIBITOR DEVELOPMENT; RISK-FACTORS; HAPLOTYPE FREQUENCIES; AMERICAN POPULATION; AFRICAN-AMERICAN; IMMUNE-RESPONSE AB The possibility of alloimmunization in patients receiving protein replacement therapy depends on (at least) three risk factors, which are necessary concomitantly but insufficient alone. The first is the degree of structural difference between the therapeutic protein and the patient's own endogenous protein, if expressed. Such differences depend on the nature of the disease mutation and the pre-mutation endogenous protein structure as well as on post-translational changes and sequence-engineered alterations in the therapeutic protein. Genetic variations in the recipients' immune systems comprise the second set of risk determinants for deleterious immune responses. For example, the limited repertoire of MHC class II isomers encoded by a given person's collection of HLA genes may or may not be able to present a 'foreign' peptide(s) produced from the therapeutic protein - following its internalization and proteolytic processing - on the surface of their antigen-presenting cells (APCs). The third (and least characterized) variable is the presence or absence of immunologic 'danger signals' during the display of foreign-peptide/MHC-complexes on APCs. A choice between existing therapeutic products or the manufacture of new proteins, which may be less immunogenic in some patients or patient populations, may require prior definition of the first two of these variables. This leads then to the possibility of developing personalized therapies for disorders due to genetic deficiencies in endogenous proteins, such as haemophilia A and B. [Correction made after online publication 11 July 2011: several critical corrections have been made to the abstract]. C1 [Howard, T. E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA. [Howard, T. E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Howard, T. E.] Univ So Calif, Keck Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90033 USA. [Yanover, C.] Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98104 USA. [Mahlangu, J.; Krause, A.] Univ Witwatersrand, Johannesburg, South Africa. [Viel, K. R.] St Josephs Translat Res Inst, Atlanta, GA USA. [Kasper, C. K.] Orthoped Hosp, Los Angeles, CA USA. [Kasper, C. K.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Pratt, K. P.] Puget Sound Blood Ctr, Seattle, WA 98104 USA. [Pratt, K. P.] Univ Washington, Div Hematol, Seattle, WA 98195 USA. RP Howard, TE (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Bldg 500,Rm 1258, Los Angeles, CA 90073 USA. EM tom.howard@va.gov RI Yanover, Chen/A-3754-2012 OI Yanover, Chen/0000-0003-3663-4286 FU ARRA [1RC2-HL101851, HL-71130, HL-72533]; Bayer Hemophilia Awards Program; CSL Behring Foundation FX We thank Drs Kenneth Mann, David Lillicrap, Georg Lemm, Arthur Thompson and Glenn Pierce for critical reading of the manuscript and helpful suggestions. Support for this study included the ARRA-funded NIH/NHLBI grant 1RC2-HL101851 (TEH and KPP), the NIH/NHLBI grants HL-71130 and HL-72533 (TEH), and grants from the Bayer Hemophilia Awards Program (KPP and TEH) and the CSL Behring Foundation (KPP). We thank the following Community Advisory Board members who reviewed the manuscript and who are providing ethical oversight for studies associated with NIH-1RC2-HL101851: Dr Louis Aledort (Chair), Ms Faye Wattleton, Ms Toni Allen-Ellingson, Ms Oleta Fitzgerald, Dr William Hobbs, and Dr Yvette Latchman. NR 47 TC 14 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD SEP PY 2011 VL 17 IS 5 BP 721 EP 728 DI 10.1111/j.1365-2516.2011.02517.x PG 8 WC Hematology SC Hematology GA 811AS UT WOS:000294174300035 PM 21649795 ER PT J AU Smith, ZA Gorgulho, AA Bezrukiy, N McArthur, D Agazaryan, N Selch, MT De Salles, AAF AF Smith, Zachary A. Gorgulho, Alessandra A. Bezrukiy, Nikita McArthur, David Agazaryan, Nzhde Selch, Michael T. De Salles, Antonio A. F. TI DEDICATED LINEAR ACCELERATOR RADIOSURGERY FOR TRIGEMINAL NEURALGIA: A SINGLE-CENTER EXPERIENCE IN 179 PATIENTS WITH VARIED DOSE PRESCRIPTIONS AND TREATMENT PLANS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Dedicated linear accelerator; Radiosurgery; Trigeminal neuralgia; Stereotactic ID GAMMA-KNIFE RADIOSURGERY; TERM-FOLLOW-UP; STEREOTACTIC RADIOSURGERY; MICROVASCULAR DECOMPRESSION; RHIZOTOMY; SURGERY; PAIN AB Purpose: Dedicated linear accelerator radiosurgery (D-LINAC) has become an important treatment for trigeminal neuralgia (TN). Although the use of gamma knife continues to he established, few large series exist using D-LINAC. The authors describe their results, comparing the effects of varied target and dose regimens. Methods and Materials: Between August 1995 and January 2008, 179 patients were treated with D-LINAC radiosurgery. Ten patients (5.58%) had no clinical follow-up. The median age was 74.0 years (range, 32-90 years). A total of 39 patients had secondary or atypical pain, and 130 had idiopathic TN. Initially. 28 patients received doses between 70 and 85 Gy, with the 30% isodose line (IDL) touching the brainstem. Then, using 90 Gy, 82 consecutive patients were treated with a 30% IDL and 59 patients with a 50% IDL tangential to the pons. Results: Of 169 patients, 134 (79.3%) experienced significant relief at a mean of 28.8 months (range, 5-142 months). Average time to relief was 1.92 months (range, immediate to 6 months). A total of 31 patients (19.0%) had recurrent pain at 13.5 months. Of 87 patients with idiopathic TN without prior procedures, 79 (90.8%) had initial relief. Among 28 patients treated with 70 Gy and 30% IDL, 18 patients (64.3%) had significant relief, and 10 (35.7%) had numbness. Of the patients with 90 Gy and 30% IDL at the brainstem, 59 (79.0%) had significant relief and 48.9% had numbness. Among 59 consecutive patients with similar dose but the 50% isodoseline at the brainstem, 49 patients (88.0%) had excellent/good relief. Numbness, averaging 2.49 on a subjective scale of 1 to 5, was experienced by 49.7% of the patients. Conclusions: Increased radiation close and volume of brainstem irradiation may improve clinical outcomes with the trade-off of trigeminal dysfunction. Further study of the implications of close and target are needed to optimize outcomes and to minimize complications. (C) 2011 Elsevier Inc. C1 [Smith, Zachary A.; Gorgulho, Alessandra A.; Bezrukiy, Nikita; McArthur, David; De Salles, Antonio A. F.] UCLA Med Ctr, Dept Neurosurg, Los Angeles, CA USA. [Agazaryan, Nzhde; Selch, Michael T.; De Salles, Antonio A. F.] UCLA Med Ctr, Dept Radiat Oncol, Los Angeles, CA USA. [De Salles, Antonio A. F.] W Los Angeles Vet Adm Hosp, Los Angeles, CA USA. RP De Salles, AAF (reprint author), Univ Calif Los Angeles, Dept Neurosurg, Ronald Reagan UCLA Med Ctr, Los Angeles, CA 90024 USA. EM adesalles@mednet.ucla.edu NR 36 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2011 VL 81 IS 1 BP 225 EP 231 DI 10.1016/j.ijrobp.2010.05.058 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 809YT UT WOS:000294093300031 PM 21236592 ER PT J AU Camp, ER Findlay, VJ Vaena, SG Walsh, J Lewin, DN Turner, DP Watson, DK AF Camp, E. Ramsay Findlay, Victoria J. Vaena, Silvia G. Walsh, Jarret Lewin, David N. Turner, David P. Watson, Dennis K. TI ASSOCIATION FOR ACADEMIC SURGERY Slug Expression Enhances Tumor Formation in a Noninvasive Rectal Cancer Model SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE colorectal cancer; e-cadherin; slug; rectal tumor model ID EPITHELIAL-MESENCHYMAL TRANSITIONS; TRANSCRIPTION FACTOR SNAIL; LYMPH-NODE METASTASIS; CELL-LINES; COLORECTAL-CANCER; RESISTANCE; CARCINOMA; DISEASE; GROWTH; MICE AB Background. Epithelial-to-mesenchymal transition (EMT) is a series of molecular changes allowing epithelial cancer cells to acquire properties of mesenchymal cells: increased motility, invasion, and protection from apoptosis. Transcriptional regulators such as Slug mediate EMT, working in part to repress E-cadherin transcription. We report a novel, noninvasive in vivo rectal cancer model to explore the role of Slug in colorectal cancer (CRC) tumor development. Methods. For the generation of DLD-1 cells overexpressing Slug (Slug DLD-1), a Slug or empty (Empty DLD-1) pCMV-3Tag-1 (kanamycin-resistant) vector was used for transfection. Cells were evaluated for Slug and E-cadherin expression, and cell migration and invasion. For the in vivo study, colon cancer cells (parental DLD-1, Slug DLD-1, empty DLD-1, and HCT-116) were submucosally injected into the posterior rectum of nude mice using endoscopic guidance. After 28 d, tumors were harvested and tissue was analyzed. Results. Slug expression in our panel of colon cancer cell lines was inversely correlated with E-cadherin expression and enhanced migration/invasion. Slug DLD-1 cells demonstrated a 21-fold increased Slug and 19-fold decreased E-cadherin expression compared with empty DLD-1. Similarly, the Slug DLD-1 cells had significantly enhanced cellular migration and invasion. In the orthotopic rectal cancer model, Slug DLD-1 cells formed rectal tumors in 9/10 (90%) of the mice (mean volume = 458 mm(3)) compared with only 1/10 (10%) with empty DLD-1 cells. Conclusion. Slug mediates EMT with enhanced in vivo rectal tumor formation. Our noninvasive in vivo model enables researchers to explore the molecular consequences of altered genes in a clinically relevant rectal cancer in an effort to develop novel therapeutic approaches for patients with rectal cancer. Published by Elsevier Inc. C1 [Camp, E. Ramsay; Vaena, Silvia G.; Walsh, Jarret] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [Findlay, Victoria J.; Lewin, David N.; Turner, David P.; Watson, Dennis K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Watson, Dennis K.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Findlay, Victoria J.; Turner, David P.; Watson, Dennis K.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Camp, E. Ramsay] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Camp, ER (reprint author), Med Univ S Carolina, Dept Surg, 25 Courtenay Dr,Room 7018,MSC 295, Charleston, SC 29425 USA. EM campe@musc.edu FU Hollings Cancer Center; American Cancer Society; Institutional Research Grant; National Institutes of Health [1K08CA142904] FX The authors acknowledge supported in part for this work by Hollings Cancer Center Translational Research Award 2008, American Cancer Society, Institutional Research Grant 2009, and the National Institutes of Health, 1K08CA142904 (ERC). NR 20 TC 11 Z9 11 U1 2 U2 7 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 SEP PY 2011 VL 170 IS 1 BP 56 EP 63 DI 10.1016/j.jss.2011.02.012 PG 8 WC Surgery SC Surgery GA 804BD UT WOS:000293627800036 PM 21470622 ER PT J AU Sarma, MK Huda, A Nagarajan, R Hinkin, CH Wilson, N Gupta, RK Frias-Martinez, E Sayre, J Guze, B Han, SH Thomas, MA AF Sarma, Manoj K. Huda, Amir Nagarajan, Rajakumar Hinkin, Charles H. Wilson, Neil Gupta, Rakesh K. Frias-Martinez, Enrique Sayre, James Guze, Barry Han, Steven-Huy Thomas, M. Albert TI Multi-dimensional MR spectroscopy: towards a better understanding of hepatic encephalopathy SO METABOLIC BRAIN DISEASE LA English DT Article DE MRS; COSY; Hepatic encephalopathy; Glutamine; Glutamate; Neuropsychological tests ID MAGNETIC-RESONANCE-SPECTROSCOPY; ACUTE LIVER-FAILURE; CIRRHOTIC-PATIENTS; H-1-NMR SPECTROSCOPY; IN-VIVO; NEUROPSYCHOLOGICAL CHARACTERIZATION; OVERT ENCEPHALOPATHY; GLUCOSE-METABOLISM; CEREBRAL AMMONIA; WORKING PARTY AB Hepatic encephalopathy (HE) is normally diagnosed by neuropsychological (NP) tests. The goals of this study were to quantify cerebral metabolites, separate glutamate (Glu) from glutamine (Gln) in patients with minimal hepatic encephalopathy (MHE) as well as healthy subjects using the prior-knowledge fitting (ProFit) algorithm on data acquired by two-dimensional (2D) localized correlated spectroscopy (L-COSY) on two different MR scanners, and to correlate the metabolite changes with neuropsychological (NP) tests. We studied 14 MHE patients and 18 healthy controls using a GE 1.5 T Signa MR scanner. Another group of 16 MHE patients and 18 healthy controls were studied using a Siemens 1.5 T Avanto MR scanner. The following parameters were used for L-COSY: TR/TE = 2 s/30 ms, 3 x 3 x 3 cm(3) voxel size, 96 Delta t(1) increments with 8 averages per Delta t(1). Using the ProFit algorithm, we were able to differentiate Gln from Glu on the GE 1.5 T data in the medial frontal white/gray matter. The ratios of myo-inositol (mI), Glu, total choline, scyllo-inositol (sI), phosphoethanolamine (PE), and total N-acetyl aspartate (NAA) showed statistically significant decline in HE patients compared to healthy controls, while the ratio of Gln was significantly increased. Similar trend was seen in the ProFit quantified Siemens 1.5 T data in the frontal and occipito-parietal white/gray regions. Among the NP domain scores, motor function, cognitive speed, executive function and the global scores showed significant differences. Excellent correlations between various NP domains and metabolite ratios were also observed. ProFit based cerebral metabolite quantitation enhances the understanding and basis of the current hypothesis of MHE. C1 [Sarma, Manoj K.; Huda, Amir; Nagarajan, Rajakumar; Wilson, Neil; Frias-Martinez, Enrique; Sayre, James; Thomas, M. Albert] Univ Calif Los Angeles, Dept Radiol Sci, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Huda, Amir] Calif State Univ Fresno, Dept Phys, Fresno, CA 93740 USA. [Hinkin, Charles H.; Guze, Barry; Thomas, M. Albert] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. [Hinkin, Charles H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Gupta, Rakesh K.] Sanjay Gandhi Postgrad Inst Med Sci, Dept Radiol, Lucknow, Uttar Pradesh, India. [Han, Steven-Huy] Univ Calif Los Angeles, David Geffen Sch Med, Dept Hepatol, Los Angeles, CA 90095 USA. RP Thomas, MA (reprint author), Univ Calif Los Angeles, Dept Radiol Sci, David Geffen Sch Med, CHS BL 428,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM athomas@mednet.ucla.edu RI Thomas, m. albert/A-6176-2012; Nagarajan, Rajakumar/A-7179-2013; Huda, Amir/I-5987-2015; Sarma, Manoj/J-8299-2014 OI Huda, Amir/0000-0002-0171-3796; FU National Institute of Mental Health (NIMH) [1R01MH06569501A1] FX This research was supported by a National Institute of Mental Health (NIMH) RO1 grant (1R01MH06569501A1). Scientific support of Drs. Nader Binesh, Kenneth Yue, Shida Banakar, and Sherry Liu during the earlier phase of this project is gratefully acknowledged. Authors acknowledge the support of Dr. Rolf Schulte, Prof. Dr. Peter Boesiger and his group members at ETH-Zurich, Switzerland in sharing the earlier version of the ProFit algorithm for processing the localized 2D J-resolved spectrum. NR 76 TC 17 Z9 18 U1 2 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD SEP PY 2011 VL 26 IS 3 BP 173 EP 184 DI 10.1007/s11011-011-9250-1 PG 12 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 811QK UT WOS:000294227800003 PM 21698453 ER PT J AU Butt, AA McGinnis, K Skanderson, M Justice, AC AF Butt, Adeel A. McGinnis, Kathleen Skanderson, Melissa Justice, Amy C. TI A Comparison of Treatment Eligibility for Hepatitis C Virus in HCV-Monoinfected Versus HCV/HIV-Coinfected Persons in Electronically Retrieved Cohort of HCV-Infected Veterans SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HEPATOCELLULAR-CARCINOMA; PEGINTERFERON ALPHA-2A; HIV; RISK; PREVALENCE; PREDICTORS; MANAGEMENT; RIBAVIRIN; CIRRHOSIS; THERAPY AB Treatment rates for hepatitis C virus (HCV) are low in actual clinical settings. However, the proportion of patients eligible for treatment, especially among those coinfected with HIV, is not well known. Our aim was to determine and compare the rates for HCV treatment eligibility among HCV and HCV-HIV-coinfected persons. We assembled a national cohort of HCV-infected veterans in care from 1998-2003, using the VA National Patient Care Database for demographic/clinical information, the Pharmacy Benefits Management database for pharmacy records, and the Decision Support Systems database for laboratory data. We compared the HCV-monoinfected and HCV-HIV-coinfected subjects for treatment indications and eligibility using current treatment guidelines. Of the 27,452 subjects with HCV and 1225 with HCV-HIV coinfection, 74.0% and 84.6% had indications for therapy and among these, 43.9% of HCV-monoinfected and 28.4% of HCV-HIV-coinfected subjects were eligible for treatment. Anemia, decompensated liver disease (DLD), chronic obstructive pulmonary disease (COPD), recent alcohol abuse, and coronary artery disease were the most common contraindications in the HCV, and anemia, DLD, renal failure, recent drug abuse, and COPD in the HCV-HIV-coinfected group. Among those eligible for treatment, only 23% of the HCV-monoinfected and 15% of the HCV-HIV-coinfected subjects received any treatment for HCV. Most veterans with HCV are not eligible for treatment according to the current guidelines. Even for those who are eligible for treatment, only a minority is prescribed treatment. Several contraindications are modifiable and aggressive management of those may improve treatment prescription rates. C1 [Butt, Adeel A.] Univ Pittsburgh, Med Ctr, Sch Med, Pittsburgh, PA 15213 USA. [Butt, Adeel A.; McGinnis, Kathleen; Skanderson, Melissa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Butt, Adeel A.] Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. RP Butt, AA (reprint author), Univ Pittsburgh, Med Ctr, Sch Med, 3601 5th Ave,Suite 3A,Falk Med Bldg, Pittsburgh, PA 15213 USA. EM aabutt@pitt.edu FU NIAAA NIH HHS [U24 AA020794] NR 30 TC 9 Z9 9 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 2011 VL 27 IS 9 BP 973 EP 979 DI 10.1089/aid.2011.0004 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 810XQ UT WOS:000294163700007 PM 21338329 ER PT J AU Pugh, MJV Starner, CI Amuan, ME Berlowitz, DR Horton, M Marcum, ZA Hanlon, JT AF Pugh, Mary Jo V. Starner, Catherine I. Amuan, Megan E. Berlowitz, Dan R. Horton, Monica Marcum, Zachary A. Hanlon, Joseph T. TI Exposure to Potentially Harmful Drug-Disease Interactions in Older Community-Dwelling Veterans Based on the Healthcare Effectiveness Data and Information Set Quality Measure: Who Is at Risk? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE drug disease interaction; HEDIS measures; potentially inappropriate prescribing; aged; pharma-coepidemiology ID INAPPROPRIATE MEDICATION USE; ELDERLY VETERANS; EMERGENCY-DEPARTMENT; CONSENSUS PANEL; ADULTS; PHARMACOTHERAPY; POPULATION; EPILEPSY; CRITERIA; FRAIL AB OBJECTIVES: To identify prevalence and risk factors for exposure to drug-disease interactions included in the Healthcare Effectiveness Data and Information Set (HEDIS) Drug-Disease Interaction (Rx-DIS) measure. DESIGN: Cross-sectional retrospective database analysis. SETTING: Outpatient clinics within the Department of Veterans Affairs (VA). PARTICIPANTS: Individuals aged 65 and older who received VA outpatient care between October 1, 2003, and September 30, 2006. MEASUREMENTS: Rx-DIS exposure based on the HEDIS measure was identified in VA patients with dementia, falls, and chronic renal failure using VA pharmacy and administrative databases. Factors associated with Rx-DIS exposure were examined, including demographic, health status, and access-to-care factors, including VA outpatient health services use and copayment status. RESULTS: Of the 305,041 older veterans who met criteria for inclusion, the 1-year prevalence of Rx-DIS exposure was 15.2%; prevalence was 20.2% for dementia, 16.2% for falls, and 8.5% for chronic renal failure. Patients with high disease burden (physical, psychiatric, number of medications) were significantly more likely to have Rx-DIS exposure, regardless of condition. Hispanics and individuals with no copayments were more likely to have Rx-DIS exposure than whites or those with required copayments. There was variation in other predictors based on the type of Rx-DIS. CONCLUSION: The prevalence of Rx-DIS was common in older VA outpatients. Future studies should examine the risk of Rx-DIS exposure on health outcomes using separate analyses for each type of Rx-DIS separately before combining all Rx-DIS into a single measure of exposure. Studies that examine the effectiveness of interventions to reduce Rx-DIS exposure will also be helpful in improving the quality of care for older adults. J Am Geriatr Soc 59: 1673-1678, 2011. C1 [Pugh, Mary Jo V.] S Texas Vet Hlth Care Syst, Vet Evidence Based Res & Implementat Ctr, San Antonio, TX 78229 USA. [Horton, Monica] S Texas Vet Hlth Care Syst, Geriatr & Extended Care, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.; Horton, Monica] Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr Gerontol & Palliat Med, Hlth Sci Ctr, San Antonio, TX 78229 USA. [Starner, Catherine I.] Prime Therapeut, Minneapolis, MN USA. [Amuan, Megan E.; Berlowitz, Dan R.] Edith Nourse Rogers Mem Vet Affairs Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Berlowitz, Dan R.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Marcum, Zachary A.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Educ & Clin Ctr, Ctr Hlth Equ Res & Geriatr Res, Pittsburgh, PA USA. RP Pugh, MJV (reprint author), S Texas Vet Hlth Care Syst, Vet Evidence Based Res & Implementat Ctr, VERDICT REAP 11C6,7400 Merton Minter, San Antonio, TX 78229 USA. EM pughm@uthscsa.edu FU VA Health Services Research [IIR-06-062]; National Institute of Aging [R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056]; National Institute of Mental Health [R34 MH082682]; National Institute of Nursing Research [R01NR010135]; Agency for Healthcare Research and Quality [R01HS017695]; Geriatric Academic Career Award [KO1 HP00114-02]; VA Health Services Research and Development Service (HSRD) [IIR 06-062]; VA HSRD [IIR-06-062, DHI 09-237, IIR-06-062 PI, PPO 09-295 PI, IIR 02-274 PI, IIR 08-274, SDR-07-042, IIR-05-121, IAF-06-080, IIR-09-335, SHP 08-140, TRX 01-091, RRP 09-112]; Epilepsy Foundation PI; Department of Defense [CDMRP 09090014]; NIH [R01-NR010828] FX This study was supported by VA Health Services Research Grant IIR-06-062. Dr. Hanlon is supported by National Institute of Aging Grants R01AG027017, P30AG024827, T32 AG021885, K07AG033174, and R01AG034056; National Institute of Mental Health Grant R34 MH082682; National Institute of Nursing Research Grant R01NR010135; and Agency for Healthcare Research and Quality Grant R01HS017695. Dr. Horton is a recipient of Geriatric Academic Career Award KO1 HP00114-02. We acknowledge the contributions of Jeffrey Tabares and Ranjani Davalath in assisting with manuscript preparation.; MJP and MH are employed by the South Texas Veterans Health Care System, DRB and MEA are employed by the Edith Nourse Rogers Memorial VA Hospital, and JTH is employed by the VA Pittsburgh Healthcare System. This study was funded by VA Health Services Research and Development Service (HSR&D) IIR 06-062.; Dr. Pugh has received research funding from VA HSR&D DHI 09-237 (PI); VA HSR&D IIR-06-062 PI, Epilepsy Foundation PI, VA HSR&D PPO 09-295 PI, VA HSR&D IIR 02-274 PI, Pugh as co-investigator: VA HSR&D IIR 08-274, VA HSR&D SDR-07-042, IIR-05-121, IAF-06-080, IIR-09-335, SHP 08-140, TRX 01-091 Department of Defense CDMRP 09090014, NIH R01-NR010828, Pugh Speaker Honoraria: 2009 Kelsey Seybold Research Foundation $400.; Dr. Berlowitz has received funding from VA HSR&D RRP 09-112 as PI, VAHSR&D IIR-06-062 as co-investigator. NR 33 TC 13 Z9 13 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2011 VL 59 IS 9 BP 1673 EP 1678 DI 10.1111/j.1532-5415.2011.03524.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 829WD UT WOS:000295615000014 PM 21831166 ER PT J AU Barnett, PG Chow, A Joyce, VR Bayoumi, AM Griffin, SC Nosyk, B Holodniy, M Brown, ST Sculpher, M Anis, AH Owens, DK AF Barnett, Paul G. Chow, Adam Joyce, Vilija R. Bayoumi, Ahmed M. Griffin, Susan C. Nosyk, Bohdan Holodniy, Mark Brown, Sheldon T. Sculpher, Mark Anis, Aslam H. Owens, Douglas K. CA OPTIMA Team TI Determinants of the Cost of Health Services Used by Veterans With HIV SO MEDICAL CARE LA English DT Article DE HIV; cost; antiretroviral therapy ID ACTIVE ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; MEDICAL-CARE; VIRAL LOAD; EXPENDITURES; MODELS; ERA; VA; PATTERNS; IMPACT AB Background: The effect of adherence, treatment failure, and comorbidities on the cost of HIV care is not well understood. Objective: To characterize the cost of HIV care including combination antiretroviral treatment (ART). Research Design: Observational study of administrative data. Subjects: Total 1896 randomly selected HIV-infected patients and 288 trial participants with multidrug-resistant HIV seen at the US Veterans Health Administration (VHA). Measures: Comorbidities, cost, pharmacy, and laboratory data. Results: Many HIV-infected patients (24.5%) of the random sample did not receive ART. Outpatient pharmacy accounted for 62.8% of the costs of patients highly adherent with ART, 32.2% of the cost of those with lower adherence, and 6.2% of the cost of those not receiving ART. Compared with patients not receiving ART, high adherence was associated with lower hospital cost, but no greater total cost. Individuals with a low CD4 count (<50 cells/mm(3)) incurred 1.9 times the cost of patients with counts >500. Most patients had medical, psychiatric, or substance abuse comorbidities. These conditions were associated with greater cost. Trial participants were less likely to have psychiatric and substance abuse comorbidities than the random sample of VHA patients with HIV. Conclusions: Patients receiving combination ART had higher medication costs but lower acute hospital cost. Poor control of HIV was associated with higher cost. The cost of psychiatric, substance abuse, rehabilitation, and long-term care and medications other than ART, often overlooked in HIV studies, was substantial. C1 [Barnett, Paul G.; Chow, Adam; Joyce, Vilija R.] VA Hlth Econ Resource Ctr, Palo Alto, CA USA. [Bayoumi, Ahmed M.] St Michaels Hosp, Ctr Res Inner City Hlth, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON, Canada. [Bayoumi, Ahmed M.] Univ Toronto, Dept Med & Hlth Policy, Toronto, ON, Canada. [Bayoumi, Ahmed M.] Univ Toronto, Dept Management, Toronto, ON, Canada. [Griffin, Susan C.; Sculpher, Mark] Univ York, Ctr Hlth Econ, York YO10 5DD, N Yorkshire, England. [Nosyk, Bohdan] St Pauls Hosp, Ctr Hlth Evaluat & Outcomes Sci, Vancouver, BC, Canada. [Brown, Sheldon T.] James J Peters VA Med Ctr, Bronx, NY USA. [Anis, Aslam H.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Bayoumi, Ahmed M.] Univ Toronto, Dept Evaluat, Toronto, ON, Canada. RP Barnett, PG (reprint author), VA Palo Alto Hlth Care Syst, HERC, 795 Willow Rd,152, Menlo Pk, CA USA. EM paul.barnett@va.gov RI Joyce, Vilija/A-2578-2013 OI Joyce, Vilija/0000-0002-2484-4625 FU US Department of Veterans Affairs; UK Medical Research Council; Canadian Institutes for Health Research FX Funding: US Department of Veterans Affairs Cooperative Studies Program, the UK Medical Research Council, and the Canadian Institutes for Health Research. NR 36 TC 9 Z9 9 U1 0 U2 1 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 SEP PY 2011 VL 49 IS 9 BP 848 EP 856 DI 10.1097/MLR.0b013e31821b34c0 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 811JX UT WOS:000294206700015 PM 21610542 ER PT J AU Allen, KD Golightly, YM Helmick, CG Ibrahim, SA Kwoh, CK Renner, JB Jordan, JM AF Allen, K. D. Golightly, Y. M. Helmick, C. G. Ibrahim, S. A. Kwoh, C. K. Renner, J. B. Jordan, J. M. TI RACIAL AND GENDER DIFFERENCES IN WILLINGNESS TO UNDERGO TOTAL JOINT REPLACEMENT: THE JOHNSTON COUNTY OSTEOARTHRITIS PROJECT SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract C1 [Allen, K. D.] Duke Univ, Med Ctr, Durham, NC USA. [Allen, K. D.] Durham VA Med Ctr, Durham, NC USA. [Golightly, Y. M.; Renner, J. B.; Jordan, J. M.] Univ N Carolina, Chapel Hill, NC USA. [Helmick, C. G.] CDC, Atlanta, GA 30333 USA. [Ibrahim, S. A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Ibrahim, S. A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kwoh, C. K.] Univ Pittsburgh, Pittsburgh, PA USA. [Kwoh, C. K.] Pittsburgh VA Hlth Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD SEP PY 2011 VL 19 SU 1 MA 342 BP S155 EP S156 PG 2 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA V33EH UT WOS:000209001600363 ER PT J AU Kwoh, CK Boudreau, R Guermazi, A Hannon, MJ Green, SM Jakicic, JM Moore, C Roemer, FW AF Kwoh, C. K. Boudreau, R. Guermazi, A. Hannon, M. J. Green, S. M. Jakicic, J. M. Moore, C. Roemer, F. W. TI IDENTIFICATION OF MRI MORPHOLOGIC FEATURES ASSOCIATED WITH DIFFERENT KNEE PAIN PATTERNS SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract C1 [Kwoh, C. K.] Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Boudreau, R.; Hannon, M. J.; Green, S. M.; Jakicic, J. M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Guermazi, A.] Boston Univ, Sch Med, Quantitat Imaging Ctr, Boston, MA 02118 USA. [Moore, C.] Texas Womans Univ, Houston, TX USA. [Roemer, F. W.] Klinikum Augsburg, Augsburg, Germany. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD SEP PY 2011 VL 19 SU 1 MA 12 BP S12 EP S13 PG 2 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA V33EH UT WOS:000209001600035 ER PT J AU Lo, GH McAlindon, TE AF Lo, G. H. McAlindon, T. E. TI KNEE ALIGNMENT MAY INFLUENCE PERI-ARTICULAR BONE MORPHOLOGY SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract C1 [Lo, G. H.] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. [Lo, G. H.] Baylor Coll Med, Houston, TX 77030 USA. [McAlindon, T. E.] Tufts Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD SEP PY 2011 VL 19 SU 1 MA 95 BP S49 EP S50 PG 2 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA V33EH UT WOS:000209001600118 ER PT J AU Shlipak, MG Coca, SG Wang, Z Devarajan, P Koyner, JL Patel, UD Thiessen-Philbrook, H Garg, AX Parikh, CR AF Shlipak, Michael G. Coca, Steven G. Wang, Zhu Devarajan, Prasad Koyner, Jay L. Patel, Uptal D. Thiessen-Philbrook, Heather Garg, Amit X. Parikh, Chirag R. CA TRIBE-AKI Consortium TI Presurgical Serum Cystatin C and Risk of Acute Kidney Injury After Cardiac Surgery SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Acute renal failure; creatinine; prognosis ID ACUTE-RENAL-FAILURE; ELDERLY PERSONS; HOSPITALIZED-PATIENTS; SURGICAL-PATIENTS; ROC CURVE; MORTALITY; BYPASS; RECLASSIFICATION; STRATIFICATION; MORBIDITY AB Background: Acute kidney injury (AKI) after cardiac surgery is associated with poor outcomes, but is challenging to predict from information available before surgery. Study Design: Prospective cohort study. Setting & Participants: The TRIBE-AKI (Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury) Consortium enrolled 1,147 adults undergoing cardiac surgery at 6 hospitals from 2007-2009; participants were selected for high AKI risk. Predictors: Presurgical values for cystatin C, creatinine, and creatinine-based estimated glomerular filtration rate (eGFR) were categorized into quintiles and grouped as "best" (quintiles 1-2), "intermediate" (quintiles 3-4), and "worst" (quintile 5) kidney function. Outcomes: The primary outcome was AKI Network (AKIN) stage 1 or higher; >= 0.3 mg/dL or 50% increase in creatinine level. Measurements: Analyses were adjusted for characteristics used clinically for presurgical risk stratification. Results: Average age was 71 +/- 10 years (mean +/- standard deviation); serum creatinine, 1.1 +/- 0.3 mg/dL; eGFR-Cr, 74 +/- 9 mL/min/1.73 m(2); and cystatin C, 0.9 +/- 0.3 mg/L. 407 (36%) participants developed AKI during hospitalization. Adjusted odds ratios for intermediate and worst kidney function by cystatin C were 1.9 (95% CI, 1.4-2.7) and 4.8 (95% CI, 2.9-7.7) compared with 1.2 (95% CI, 0.9-1.7) and 1.8 (95% CI, 1.2-2.6) for creatinine and 1.0 (95% CI, 0.7-1.4) and 1.7 (95% CI, 1.1-2.3) for eGFR-Cr categories, respectively. After adjustment for clinical predictors, the C statistic to predict AKI was 0.70 without kidney markers, 0.69 with creatinine, and 0.72 with cystatin C. Cystatin C also substantially improved AKI risk classification compared with creatinine, based on a net reclassification index of 0.21 (P < 0.001). Limitations: The ability of these kidney biomarkers to predict risk of dialysis-requiring AKI or death could not be assessed reliably in our study because of a small number of patients with either outcome. Conclusions: Presurgical cystatin C is better than creatinine or creatinine-based eGFR at forecasting the risk of AKI after cardiac surgery. Am J Kidney Dis. 58(3): 366-373. 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 [Coca, Steven G.; Wang, Zhu; Parikh, Chirag R.] Yale Univ, Nephrol Sect, West Haven, CT 06516 USA. [Coca, Steven G.; Wang, Zhu; Parikh, Chirag R.] VAMC, West Haven, CT 06516 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Devarajan, Prasad] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Koyner, Jay L.] Univ Chicago, Pritzker Sch Med, Dept Med, Nephrol Sect, Chicago, IL 60637 USA. [Patel, Uptal D.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Thiessen-Philbrook, Heather; Garg, Amit X.] Univ Western Ontario, Div Nephrol, Dept Med, London, ON, Canada. [Thiessen-Philbrook, Heather; Garg, Amit X.] Univ Western Ontario, Div Nephrol, Dept Epidemiol, London, ON, Canada. [Thiessen-Philbrook, Heather; Garg, Amit X.] Univ Western Ontario, Div Nephrol, Dept Biostat, London, ON, Canada. RP Parikh, CR (reprint author), Yale Univ, Nephrol Sect, 950 Campbell Ave,Mail Code 151B,Bldg 35A,Rm 219, West Haven, CT 06516 USA. EM chirag.parikh@yale.edu OI Wang, Zhu/0000-0002-0773-0052 FU American Heart Association; National Heart, Lung, and Blood Institute [RO1HL-085757]; National Center for Research Resources [UL1 RR024139] FX The research reported in this article was supported by the American Heart Association Clinical Development award and grant RO1HL-085757 from the National Heart, Lung, and Blood Institute. The study was also supported by Clinical Translational Science Award grant number UL1 RR024139 from the National Center for Research Resources. The granting agencies did not participate in the protocol development, analysis, and interpretation of the results. NR 29 TC 36 Z9 37 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2011 VL 58 IS 3 BP 366 EP 373 DI 10.1053/j.ajkd.2011.03.015 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 809KW UT WOS:000294055100009 PM 21601336 ER PT J AU Kraut, JA Xing, SX AF Kraut, Jeffrey A. Xing, Shelly Xiaolei TI Approach to the Evaluation of a Patient With an Increased Serum Osmolal Gap and High-Anion-Gap Metabolic Acidosis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE High-anion-gap metabolic acidosis; serum osmolality; osmolal gap; ketoacidosis; methanol; ethylene glycol; diethylene glycol; propylene glycol; isopropanol ID ETHYLENE-GLYCOL; ALCOHOLIC KETOACIDOSIS; ETHANOL INGESTION; METHANOL; DIAGNOSIS; INTOXICATIONS AB An increase in serum osmolality and serum osmolal gap with or without high-anion-gap metabolic acidosis is an important clue to exposure to one of the toxic alcohols, which include methanol, ethylene glycol, diethylene glycol, propylene glycol, or isopropanol. However, the increase in serum osmolal gap and metabolic acidosis can occur either together or alone depending on several factors, including baseline serum osmolal gap, molecular weight of the alcohol, and stage of metabolism of the alcohol. In addition, other disorders, including diabetic or alcoholic ketoacidosis, acute kidney injury, chronic kidney disease, and lactic acidosis, can cause high-anion-gap metabolic acidosis associated with an increased serum osmolal gap and therefore should be explored in the differential diagnosis. It is essential for clinicians to understand the value and limitations of osmolal gap to assist in reaching the correct diagnosis and initiating appropriate treatment. In this teaching case, we present a systematic approach to diagnosing high serum osmolality and increased serum osmolal gap with or without high-anion-gap metabolic acidosis. Am J Kidney Dis. 58(3): 480-484. 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 [Kraut, Jeffrey A.; Xing, Shelly Xiaolei] VHAGLA Healthcare Syst, Div Nephrol, Los Angeles, CA 90073 USA. [Kraut, Jeffrey A.; Xing, Shelly Xiaolei] Vet Adm Greater Los Angeles VHAGLA Healthcare Sys, Med Serv, Los Angeles, CA USA. [Kraut, Jeffrey A.; Xing, Shelly Xiaolei] Vet Adm Greater Los Angeles VHAGLA Healthcare Sys, Res Serv, Los Angeles, CA USA. [Kraut, Jeffrey A.] UCLA Membrane Biol Lab, Los Angeles, CA USA. [Kraut, Jeffrey A.] UCLA David Geffen Sch Med Sci Los Angeles, Los Angeles, CA USA. RP Kraut, JA (reprint author), VHAGLA Healthcare Syst, Div Nephrol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jkraut@ucla.edu FU Veterans Administration FX This work was supported in part by research funds provided by the Veterans Administration. NR 27 TC 11 Z9 11 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2011 VL 58 IS 3 BP 480 EP 484 DI 10.1053/j.ajkd.2011.05.018 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 809KW UT WOS:000294055100023 PM 21794966 ER PT J AU Meszaros, ZS Dimmock, JA Ploutz-Snyder, RJ Abdul-Malak, Y Leontieva, L Canfield, K Batki, SL AF Meszaros, Zsuzsa Szombathyne Dimmock, Jacqueline A. Ploutz-Snyder, Robert J. Abdul-Malak, Ynesse Leontieva, Luba Canfield, Kelly Batki, Steven L. TI Predictors of Smoking Severity in Patients with Schizophrenia and Alcohol Use Disorders SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID PSYCHIATRIC-DISORDERS; CIGARETTE-SMOKING; TOBACCO USE; DEPRESSION; CESSATION; SCALE; COMORBIDITY; MEDICATION; DEPENDENCE; BEHAVIORS AB The goal of the present study was to identify predictors of smoking severity in patients with schizophrenia and co-occurring alcohol use disorders (AUD). Our hypothesis was that negative symptoms of schizophrenia, severity of depression, male gender, drinking severity, and recreational drug use were associated with increased smoking. Clinical data, including demographic variables, alcohol and substance use severity, psychiatric medications, severity of depression, positive and negative symptoms of schizophrenia were analyzed in a cohort of 90 patients with schizophrenia or schizoaffective disorder and AUD. Eighty-eight percent of participants were smokers, they smoked an average of 15 cigarettes/day. Zero-inflated negative binomial (ZINB) regression analyses demonstrated that alcohol use severity, gender, and severity of negative symptoms were not predictive of the number of cigarettes smoked. Smoking severity was positively related to Caucasian race, psychosis severity (Positive and Negative Syndrome Scale [PANSS] general score), and medications (conventional antipsychotics). Subjects who used recreational drugs smoked less. In summary, severe, treatment resistant schizophrenia, and conventional antipsychotic treatment is associated with heavy smoking in patients with schizophrenia and AUD regardless of gender or alcohol use. (Am J Addict 2011; 20: 462-467) C1 [Meszaros, Zsuzsa Szombathyne; Dimmock, Jacqueline A.; Abdul-Malak, Ynesse; Leontieva, Luba; Canfield, Kelly; Batki, Steven L.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Ploutz-Snyder, Robert J.] Univ Space Res Assoc, Space Life Sci Div, Houston, TX USA. [Ploutz-Snyder, Robert J.] SUNY Upstate Med Univ, Dept Med, Syracuse, NY USA. [Batki, Steven L.] UCSF Dept Psychiat, San Francisco, CA USA. [Batki, Steven L.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Meszaros, ZS (reprint author), SUNY Upstate Med Univ, Dept Psychiat, 750 E Adams St, Syracuse, NY 13210 USA. EM meszaroz@upstate.edu FU NIAAA NIH HHS [R01 AA013655, R01 AA013655-01A1] NR 33 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD SEP-OCT PY 2011 VL 20 IS 5 BP 462 EP 467 DI 10.1111/j.1521-0391.2011.00150.x PG 6 WC Substance Abuse SC Substance Abuse GA 807FO UT WOS:000293881900010 PM 21838846 ER PT J AU Gallagher, CL Johnson, SC Bendlin, BB Chung, MK Holden, JE Oakes, TR Brooks, BR Konopacki, RA Dogan, S Abbs, JH Xu, GF Nickles, RJ Pyzalski, RW DeJesus, OT Brown, WD AF Gallagher, Catherine L. Johnson, Sterling C. Bendlin, Barbara B. Chung, Moo K. Holden, James E. Oakes, Terrence R. Brooks, Benjamin R. Konopacki, Richard A. Dogan, Selami Abbs, James H. Xu, Guofan Nickles, Robert J. Pyzalski, Robert W. DeJesus, Onofre T. Brown, W. Douglas TI A longitudinal study of motor performance and striatal [18F]fluorodopa uptake in Parkinson's disease SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Fluorodopa; Motor control; Parkinson's disease; Positron emission tomography; Ageing; Tongue/*physiopathology; Facial Muscles/*physiopathology ID REACTION-TIME; BASAL GANGLIA; MOVEMENT; PROGRESSION; DOPAMINE; FORCE; ONSET; PET; ABNORMALITIES; BRADYKINESIA AB Although [F-18]fluoro-l-dopa [FDOPA] positron emission tomography (PET) has been used as a surrogate outcome measure in Parkinson's disease therapeutic trials, this biomarker has not been proven to reflect clinical status longitudinally. We completed a retrospective analysis of relationships between computerized sampling of motor performance, FDOPA PET, and clinical outcome scales, repeated over 4 years, in 26 Parkinson's disease (PD) patients and 11 healthy controls. Mixed effects analyses showed that movement time and tongue strength best differentiated PD from control subjects. In the treated PD cohort, motor performance measures changed gradually in contrast to a steady decline in striatal FDOPA uptake. Prolonged reaction and movement time were related to lower caudate nucleus FDOPA uptake, and abnormalities in hand fine force control were related to mean striatal FDOPA uptake. These findings provide evidence that regional loss of nigrostriatal inputs to frontostriatal networks affects specific aspects of motor function. C1 [Gallagher, Catherine L.; Abbs, James H.] Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Johnson, Sterling C.; Bendlin, Barbara B.; Xu, Guofan] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53792 USA. [Johnson, Sterling C.; Bendlin, Barbara B.; Xu, Guofan] Univ Wisconsin, Dept Med, Madison, WI 53706 USA. [Chung, Moo K.; Konopacki, Richard A.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA. [Chung, Moo K.; Oakes, Terrence R.] Waisman Ctr Brain Imaging & Behav, Madison, WI USA. [Holden, James E.; Nickles, Robert J.; DeJesus, Onofre T.] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. [Brooks, Benjamin R.] Carolinas Neuromuscular ALS MDA Ctr, Charlotte, NC USA. [Dogan, Selami] Aurora Sinai Med Ctr, Milwaukee, WI USA. [Pyzalski, Robert W.] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA. [Brown, W. Douglas] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. RP Gallagher, CL (reprint author), Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, Madison, WI 53706 USA. EM gallagher@neurology.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875; Johnson, Sterling/0000-0002-8501-545X FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Science Research and Development Service; National Institutes of Health [1R29NS31612]; University of Wisconsin Institute for Clinical and Translational Research through National Institutes of Health [1UL1RR025011] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Science Research and Development Service [grant to C.G]; National Institutes of Health [grant number 1R29NS31612 to D.B] and University of Wisconsin Institute for Clinical and Translational Research, funded through a National Institutes of Health Clinical and Translational Science Award, [grant number 1UL1RR025011 to C.G.]. NR 47 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD SEP PY 2011 VL 5 IS 3 BP 203 EP 211 DI 10.1007/s11682-011-9124-5 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA 802GY UT WOS:000293498500005 PM 21556744 ER PT J AU Medverd, JR Ngo, AV Bhargava, P AF Medverd, J. R. Ngo, A-V Bhargava, P. TI An unusual cause of persistent subcutaneous fluid collection SO BRITISH JOURNAL OF RADIOLOGY LA English DT Editorial Material ID MOREL-LAVALLEE LESION; DEGLOVING INJURIES; MANAGEMENT C1 [Medverd, J. R.; Ngo, A-V; Bhargava, P.] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Medverd, J. R.; Bhargava, P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Medverd, JR (reprint author), VA Puget Sound Hlth Care Ctr, Mail Box 358280,S-114-RAD,1660 S Columbian Way, Seattle, WA 98108 USA. EM jmed@u.washington.edu RI Bhargava, Puneet /F-1330-2011 OI Bhargava, Puneet/0000-0002-3849-9666 NR 9 TC 3 Z9 3 U1 0 U2 3 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD SEP PY 2011 VL 84 IS 1005 BP 864 EP 866 DI 10.1259/bjr/29764457 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 807ZY UT WOS:000293943400022 PM 21849371 ER PT J AU Locke, C McEuen, J Felder, RS Lesselroth, B Barrett, TW Stevens, B Pope, DS AF Locke, Christy McEuen, Judy Felder, Robert S. Lesselroth, Blake Barrett, Thomas W. Stevens, Brent Pope, Diana S. TI Evaluating an Insulin Infusion Protocol in an Acute Care Setting SO CLINICAL NURSE SPECIALIST LA English DT Article DE hospitalization; hyperglycemia; nursing protocols ID ASSOCIATION CONSENSUS STATEMENT; GLYCEMIC CONTROL AB Objective: The objective of the present study was to evaluate the adherence, safety, and effectiveness of a paper versus an electronic insulin infusion protocol. Design: This quasi-experimental implementation study compared experimental and control groups using a nonrandomized prospective cohort design. Setting: The study was performed at 2 surgical units within a federal tertiary care teaching hospital. Sample: Fifty-eight registered nurses volunteered. Methods: We compared time intervals using electronic time stamps from glucometers and insulin infusion devices to measure protocol adherence. We assessed perceived adherence using a nurse survey, and, to evaluate safety, we reviewed each paper protocol infusion calculation for correctness. Findings: Median times from blood glucose acquisition to infusion rate adjustment did not differ significantly between groups (P = .215). The majority of infusions (96.6%) had glucose acquisition times within the acceptable range. Median values of time to next "glucose due" did not differ significantly (P = .88), and relative variation in median glucose reporting times did not differ significantly between groups (P = .16). Evaluation of 877 paper protocol entries demonstrated a 10.7% (n = 94) calculation error rate. Registered nurses within the electronic group reported greater ease in balancing workload when compared with paper protocol use (P = .03). Attitudes did not differ significantly between groups in areas of determining infusion adjustment, bolus insulin dose, next glucose due, ease of access, understanding protocol, or overall satisfaction. Conclusions: This study demonstrates that one can adhere to an insulin infusion protocol, regardless of the format (paper or electronic), in the medical-surgical setting. Our results suggest there are safety and nurse workload benefits when an electronic protocol was used. Implications: Adherence, safety, and effectiveness can be achieved when using insulin infusion in the medical-surgical setting. C1 [Locke, Christy; McEuen, Judy; Lesselroth, Blake; Barrett, Thomas W.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Locke, Christy; Felder, Robert S.; Stevens, Brent; Pope, Diana S.] Portland VA Med Ctr, Portland, OR USA. RP Locke, C (reprint author), 22117 NE 267th Ct, Battle Ground, WA 98604 USA. EM christine.locke@va.gov FU Quality Enhancement Research Initiative (QUERI), Office of Research and Development, Veterans Health Administration FX This study was funded through the Quality Enhancement Research Initiative (QUERI), Office of Research and Development, Veterans Health Administration ($27 000). NR 16 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD SEP-OCT PY 2011 VL 25 IS 5 BP 237 EP 243 DI 10.1097/NUR.0b013e3182299522 PG 7 WC Nursing SC Nursing GA 808DT UT WOS:000293957500007 PM 22649844 ER PT J AU Ahmadi, N Mao, SS Hajsadeghi, F Hacioglu, Y Flores, F Gao, YL Ebrahimi, R Budoff, M AF Ahmadi, Naser Mao, Song S. Hajsadeghi, Fereshteh Hacioglu, Yalcin Flores, Ferdinand Gao, Yanlin Ebrahimi, Ramin Budoff, Matthew TI Relation of subclinical left and right ventricular dysfunctions measured by computed tomography angiography with the severity of coronary artery disease SO CORONARY ARTERY DISEASE LA English DT Article DE computed tomography angiography; coronary artery calcium; coronary artery disease; subclinical right and left ventricular dysfunction ID CONGESTIVE-HEART-FAILURE; MYOCARDIAL BLOOD-FLOW; MAGNETIC-RESONANCE; SYSTOLIC FUNCTION; ELECTRON-BEAM; PROGNOSTIC IMPLICATIONS; CARDIOVASCULAR-DISEASE; INOTROPIC RESERVE; INFARCTION; MORTALITY AB Objective Ventricular dysfunction in asymptomatic patients is directly linked to the eventual development of symptomatic congestive heart failure. This study investigates whether subclinical left ventricular (LV) and right ventricular (RV) dysfunctions measured by computed tomography angiography is associated with the severity of coronary artery disease (CAD). Methods and results We studied 1608 consecutive patients with suspected CAD (age 62 +/- 10 years, 64% male), who underwent coronary artery calcium (CAC) scanning and computed tomography angiography. RV and LV volumes at end systole and end diastole were measured, and stroke volume and ejection fraction were calculated using the Simpson method and piecewise smooth subdivision surface (PSSS) method. Analysis by Simpson was performed on short axis and apical four-chamber views. Axial images were used to measure RV and LV volumes by the PSSS method. CAD was defined as normal, nonobstructive, and obstructive (0% stenosis, luminal stenosis 1-49 and 50%+, respectively). There was a strong agreement between PSSS and Simpson method RV ejection fraction (RVEF) and LV ejection fraction (LVEF) measurement. RVEF and LVEF decreased proportionally from CAC 0 to CAC 100+, also from normal-to-diseased coronaries (P=0.001). After adjustment for cardiovascular risk factors, the mean LVEF and RVEF decreased 2.8 and 2.4%, respectively in CAC 100+ compared with CAC 0. Similarly, LVEF and RVEF decreased significantly in nonobstructive CAD (-3.5 and -3.1%, respectively) and obstructive CAD (-5.9 and -4.5%, respectively) compared with normal coronaries, respectively (P<0.05). The relative risk of each 5% decrease in LVEF and RVEF was 1.33 and 1.29 for nonobstructive CAD and 1.54 and 1.33 for obstructive CAD, respectively. Conclusion The presence and severity of coronary atherosclerosis is significantly associated with subclinical RV and LV dysfunctions. Coron Artery Dis 22: 380-387 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Ahmadi, Naser; Mao, Song S.; Hajsadeghi, Fereshteh; Hacioglu, Yalcin; Flores, Ferdinand; Gao, Yanlin; Budoff, Matthew] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. [Ebrahimi, Ramin] Univ Calif Los Angeles, Los Angeles, CA USA. [Ebrahimi, Ramin] Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Ahmadi, N (reprint author), Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, 1124 W Carson St,RB2, Torrance, CA 90502 USA. EM nahmadi@labiomed.org NR 37 TC 1 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0954-6928 EI 1473-5830 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD SEP PY 2011 VL 22 IS 6 BP 380 EP 387 DI 10.1097/MCA.0b013e328347506f PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 802HC UT WOS:000293498900002 PM 21666441 ER PT J AU Marcum, ZA Fried, LF AF Marcum, Zachary A. Fried, Linda F. TI Aging and antihypertensive medication-related complications in the chronic kidney disease patient SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE adverse drug events; aging; antihypertensives; chronic kidney disease; older adults ID ISOLATED SYSTOLIC HYPERTENSION; CONVERTING-ENZYME-INHIBITORS; HIGH BLOOD-PRESSURE; ELDERLY-PATIENTS; HYPERKALEMIA RISK; RANDOMIZED-TRIAL; DOUBLE-BLIND; OLDER; HYPOTENSION; MORTALITY AB Purpose of review We have reviewed the recent literature to describe the potential medication errors and adverse drug events (ADEs) associated with antihypertensives among older adults with chronic kidney disease (CKD). Recent findings Overall, few studies have been published describing ADEs in older adults with CKD. Several examined hyperkalemia associated with angiotensin-converting enzyme (ACE)-inhibitor/angiotensin II receptor blocker (ARB), diuretic (potassium-sparing), and beta-blocker use. Additional studies described acute kidney injury (AKI) most commonly with ACE-inhibitor/ARB therapy. Finally, orthostatic hypotension was evaluated in those taking ACE-inhibitor/ARB, b-blocker, or calcium-channel blocker therapy. In the absence of robust literature examining these events in this understudied population, one must consider age-related antihypertensive pharmacokinetic/pharmacodynamic profiles concomitantly with the patient's comorbidities and other medications in order to minimize the risk for potential medication errors, drug-drug interactions, and ADEs. Summary Some of the most common ADEs associated with antihypertensive use in older adults with CKD include hyperkalemia, AKI, and orthostatic hypotension. Diligent monitoring of laboratory data, vital signs, and potential drug-drug interactions may mitigate serious ADEs caused by antihypertensives in this high-risk patient population. C1 [Marcum, Zachary A.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA 15213 USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Fried, Linda F.] Univ Pittsburgh, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Fried, Linda F.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. RP Marcum, ZA (reprint author), Univ Pittsburgh, Sch Med, Dept Med Geriatr Med, Kaufmann Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA. EM zam12@pitt.edu FU National Institute on Aging [T32 AG021885] FX This review was supported by funding from the National Institute on Aging (T32 AG021885). NR 38 TC 12 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD SEP PY 2011 VL 20 IS 5 BP 449 EP 456 DI 10.1097/MNH.0b013e32834902ad PG 8 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 806CC UT WOS:000293779100001 PM 21670671 ER PT J AU Alemi, F Kwon, E Chiu, J Aoki, H Stewart, L Corvera, CU AF Alemi, Farzad Kwon, Edwin Chiu, Jonathan Aoki, Hisae Stewart, Lygia Corvera, Carlos U. TI Laparoscopic treatment of liver tumours using a two-needle probe bipolar radiofrequency ablation device SO HPB LA English DT Article DE hepatocellular carcinoma; liver resection; liver ID PERCUTANEOUS ETHANOL INJECTION; SMALL HEPATOCELLULAR-CARCINOMA; UNRESECTABLE TUMORS; HEPATIC RESECTION; PORCINE LIVER; HABIB(TM) 4X; IN-VIVO; COMPLICATIONS; METASTASES; CLASSIFICATION AB Background: Many hepatobiliary centres are increasingly utilizing thermocoagulative devices such as bipolar-radiofrequency ablation (B-RFA). Compared with monopolar-radiofrequency ablation (M-RFA), B-RFA does not require grounding pads, thereby avoiding dermal burn injuries, and does not position probes directly into the tumour but rather on the perimeter. Additionally, B-RFA can precoagulate parenchyma to assist in hepatic resection. Herein, we report our early experience using B-RFA. Methods: A retrospective review identified 68 patients who underwent M-RFA or B-RFA between June 2004 and September 2010 in an academic centre. Peri-operative metrics were analysed. Results: M-RFA was used to treat 30 patients, whereas B-RFA was used for 17 patients. There were no differences in peri-operative metrics, survival or disease recurrence between M-RFA and B-RFA. Seventeen additional patients underwent B-RFA precoagulation during laparoscopic resection (segmentectomy in eleven patients and multi-segmental resection in six patients). Four patients with multifocal disease underwent procedures that combined B-RFA with resection. Conclusions: The early experience utilizing B-RFA demonstrates equivalency to M-RFA with respect to peri-operative metrics and survival. Moreover, B-RFA can be utilized to precoagulate tissue during a planned resection, making it not only a useful tool for tumour therapy but also a useful adjunct during surgical resections. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Corvera, CU (reprint author), 4150 Clement St, San Francisco, CA 94121 USA. EM carlos.corvera@ucsfmedctr.org FU Veterans Health Administration; Northern California Institute for Research and Education FX A grant from the Veterans Health Administration and the Northern California Institute for Research and Education. Communication: Originally presented at Americas HPBA Conference March 2011, Miami, Fl USA. NR 33 TC 4 Z9 4 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1365-182X EI 1477-2574 J9 HPB JI HPB PD SEP PY 2011 VL 13 IS 9 BP 656 EP 664 DI 10.1111/j.1477-2574.2011.00347.x PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 807OR UT WOS:000293909800011 PM 21843267 ER PT J AU Lynch, CP Egede, LE AF Lynch, Cheryl P. Egede, Leonard E. TI Optimizing Diabetes Self-care in Low Literacy and Minority Populations-Problem-solving, Empowerment, Peer Support and Technology-based Approaches SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID RANDOMIZED-TRIAL; HEALTH LITERACY; MANAGEMENT; INTERVENTIONS; VETERANS; OUTCOMES; AFFAIRS C1 [Lynch, Cheryl P.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Lynch, Cheryl P.; Egede, Leonard E.] Ralph H Johnson VAMC, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Lynch, Cheryl P.; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU NIDDK NIH HHS [K24 DK093699] NR 25 TC 7 Z9 7 U1 0 U2 7 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 SEP PY 2011 VL 26 IS 9 BP 953 EP 955 DI 10.1007/s11606-011-1759-9 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 808WW UT WOS:000294013700004 PM 21647745 ER PT J AU Morasco, BJ Duckart, JP Dobscha, SK AF Morasco, Benjamin J. Duckart, Jonathan P. Dobscha, Steven K. TI Adherence to Clinical Guidelines for Opioid Therapy for Chronic Pain in Patients with Substance Use Disorder SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE chronic pain; substance use disorder; opioids; treatment guidelines; medical utilization ID CHRONIC NONCANCER PAIN; LOW-BACK-PAIN; PRIMARY-CARE; ADMINISTRATIVE DATA; MEDICATION MISUSE; MANAGEMENT; HEALTH; PRESCRIPTIONS; COMORBIDITY; IMPROVEMENT AB BACKGROUND: Patients with chronic non-cancer pain (CNCP) have high rates of substance use disorders (SUD). SUD complicates pain treatment and may lead to worse outcomes. However, little information is available describing adherence to opioid treatment guidelines for CNCP generally, or guideline adherence for patients with comorbid SUD. OBJECTIVE: Examine adherence to clinical guidelines for opioid therapy over 12 months, comparing patients with SUD diagnoses made during the prior year to patients without SUD. DESIGN: Cohort study. PARTICIPANTS: Administrative data were collected from veterans with CNCP receiving treatment within a Veterans Affairs regional healthcare network who were prescribed chronic opioid therapy in 2008 (n = 5814). KEY RESULTS: Twenty percent of CNCP patients prescribed chronic opioid therapy had a prior-year diagnosis of SUD. Patients with SUD were more likely to have pain diagnoses and psychiatric comorbidities. In adjusted analyses, patients with SUD were more likely than those without SUD to have had a mental health appointment (29.7% versus 17.2%, OR = 1.49, 95% CI = 1.26-1.77) and a urine drug screen (UDS) (47.0% versus 18.2%, OR = 3.53, 95% CI = 3.06-4.06) over 12 months. There were no significant differences between groups on receiving more intensive treatment in primary care (63.4% versus 61.0%), long-acting opioids (26.9% versus 26.0%), prescriptions for antidepressants (88.2% versus 85.8%, among patients with depression), or participating in physical therapy (30.6% versus 28.6%). Only 35% of patients with SUD received substance abuse treatment. CONCLUSIONS: CNCP patients with SUD were more likely to have mental health appointments and receive UDS monitoring, but not more likely to participate in other aspects of pain care compared to those without SUD. Given data suggesting patients with comorbid SUD may need more intensive treatment to achieve improvements in pain-related function, SUD patients may be at high risk for poor outcomes. C1 [Morasco, Benjamin J.; Dobscha, Steven K.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Morasco, Benjamin J.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Duckart, Jonathan P.; Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, Portland, OR USA. RP Morasco, BJ (reprint author), Portland VA Med Ctr R&D99, Mental Hlth & Clin Neurosci Div, 3710 SW US Vet Hosp Rd, Portland, OR USA. EM benjamin.morasco@va.gov FU National Institute on Drug Abuse [K23DA023467]; VA Health Services Research and Development service [REA 06174]; Oregon Clinical and Translational Research Institute; National Center for Research Resources, a component of the National Institutes of Health and NIH Roadmap for Medical Research [Ul1RR024140] FX This study was supported in part by award K23DA023467 from the National Institute on Drug Abuse to Dr. Morasco. Jonathan Duckart, MPS, was supported by grant REA 06174 from the VA Health Services Research and Development service. The authors appreciate support provided from the Oregon Clinical and Translational Research Institute, grant number Ul1RR024140 from the National Center for Research Resources, a component of the National Institutes of Health and NIH Roadmap for Medical Research. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health or the Department of Veterans Affairs. NR 42 TC 30 Z9 30 U1 1 U2 10 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 SEP PY 2011 VL 26 IS 9 BP 965 EP 971 DI 10.1007/s11606-011-1734-5 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 808WW UT WOS:000294013700008 PM 21562923 ER PT J AU Wang, EA McGinnis, KA Fiellin, DA Goulet, JL Bryant, K Gibert, CL Leaf, DA Mattocks, K Sullivan, LE Vogenthaler, N Justice, AC AF Wang, Emily A. McGinnis, Kathleen A. Fiellin, David A. Goulet, Joseph L. Bryant, Kendall Gibert, Cynthia L. Leaf, David A. Mattocks, Kristin Sullivan, Lynn E. Vogenthaler, Nicholas Justice, Amy C. CA VACS Project Team TI Food Insecurity is Associated with Poor Virologic Response among HIV-Infected Patients Receiving Antiretroviral Medications SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE food insecurity; HIV; patients; antiretrovirals ID HOUSING INSTABILITY; ALCOHOL-CONSUMPTION; WELFARE RECIPIENTS; PHARMACY RECORDS; MENTAL-HEALTH; SAN-FRANCISCO; WEIGHT-LOSS; ADHERENCE; HIV/AIDS; INSUFFICIENCY AB BACKGROUND AND OBJECTIVE: Food insecurity negatively impacts HIV disease outcomes in international settings. No large scale U.S. studies have investigated the association between food insecurity and severity of HIV disease or the mechanism of this possible association. The objective of this study was to examine the impact of food insecurity on HIV disease outcomes in a large cohort of HIV-infected patients receiving antiretroviral medications. DESIGN: This is a cross-sectional study. PARTICIPANTS AND SETTING: Participants were HIV-infected patients enrolled in the Veterans Aging Cohort Study between 2002-2008 who were receiving antiretroviral medications. MAIN MEASUREMENTS: Participants reporting "concern about having enough food for you or your family in the past 30 days" were defined as food insecure. Using multivariable logistic regression, we explored the association between food insecurity and both low CD4 counts (< 200 cells/mu L) and unsuppressed HIV-1 RNA (> 500 copies/mL). We then performed mediation analysis to examine whether antiretroviral adherence or body mass index mediates the observed associations. KEY RESULTS: Among 2353 HIV-infected participants receiving antiretroviral medications, 24% reported food insecurity. In adjusted analyses, food insecure participants were more likely to have an unsuppressed HIV-1 RNA (AOR 1.37, 95% CI 1.09, 1.73) compared to food secure participants. Mediation analysis revealed that neither antiretroviral medication adherence nor body mass index contributes to the association between food insecurity and unsuppressed HIV-1 RNA. Food insecurity was not independently associated with low CD4 counts. CONCLUSIONS: Among HIV-infected participants receiving antiretroviral medications, food insecurity is associated with unsuppressed viral load and may render treatment less effective. Longitudinal studies are needed to test the potential causal association between food insecurity, lack of virologic suppression, and additional HIV outcomes. C1 [Wang, Emily A.; Fiellin, David A.; Goulet, Joseph L.; Mattocks, Kristin; Sullivan, Lynn E.; Justice, Amy C.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [McGinnis, Kathleen A.] Pittsburgh VA Healthcare Syst, Pittsburgh, PA USA. [Goulet, Joseph L.; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Bryant, Kendall] NIAAA, NIH, Rockville, MD 20852 USA. [Gibert, Cynthia L.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Gibert, Cynthia L.] VA Med Ctr, Washington, DC USA. [Leaf, David A.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Vogenthaler, Nicholas] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA. RP Wang, EA (reprint author), Yale Univ, Sch Med, Dept Internal Med, Harkness Hall Bldg A 367 Cedar St,Suite 410A, New Haven, CT 06510 USA. EM emily.wang@yale.edu RI Nguyen, Giang/D-9027-2016 OI Goulet, Joseph/0000-0002-0842-804X; Fiellin, David/0000-0002-4006-010X FU National Institute on Alcohol and Alcohol Abuse [U01 AA 13566, U10 AA 13566]; National Institute of Aging [K23 AG00826]; Robert Wood Johnson Generalist Faculty Scholar Award; NIA; National Institute of Mental Health; VA HSR&D Research Enhancement Award Program (REAP) PRIME Project [REA 08-266] FX This work was funded by National Institute on Alcohol and Alcohol Abuse (U01 AA 13566 and U10 AA 13566), National Institute of Aging (K23 AG00826), Robert Wood Johnson Generalist Faculty Scholar Award, an Inter-agency Agreement between NIA, National Institute of Mental Health, and VA HSR&D Research Enhancement Award Program (REAP) PRIME Project (REA 08-266). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 36 TC 41 Z9 41 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2011 VL 26 IS 9 BP 1012 EP 1018 DI 10.1007/s11606-011-1723-8 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 808WW UT WOS:000294013700015 PM 21573882 ER PT J AU Melrose, RJ Ettenhofer, ML Harwood, D Achamallah, N Campa, O Mandelkern, M Sultzer, DL AF Melrose, Rebecca J. Ettenhofer, Mark L. Harwood, Dylan Achamallah, Natalie Campa, Olivia Mandelkern, Mark Sultzer, David L. TI Cerebral Metabolism, Cognition, and Functional Abilities in Alzheimer Disease SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE Alzheimer disease; IADLs; functional ability; cerebral metabolism; cognition ID PREDICT INSTRUMENTAL ACTIVITIES; DORSOLATERAL PREFRONTAL CORTEX; POSTERIOR PARIETAL CORTEX; MINI-MENTAL-STATE; SHORT-TERM-MEMORY; EXECUTIVE DYSFUNCTION; NEUROPSYCHOLOGICAL PERFORMANCE; MILD DEMENTIA; OLDER-ADULTS; IMPAIRMENT AB Patients with Alzheimer disease (AD) exhibit profound difficulties in completing instrumental activities of daily living (IADLs), such as managing finances, organizing medications, and food preparation. It is unclear which brain areas underlie IADL deficits in AD. To address this question, we used voxel-based analysis to correlate the performance of IADLs with resting cerebral metabolism as measured during [F-18] fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging in 44 patients with AD. Poorer ability to complete IADLs was associated with hypometabolism in right-sided cortical regions, including the parietal lobe, posterior temporal cortex, dorsolateral prefrontal cortex, and frontal pole. Follow-up path analyses examining anatomically defined regions of interest (ROI) demonstrated that the association between metabolism and IADLs was mediated by global cognition in frontal ROIs, and partially mediated by global cognition in the parietal ROI. Findings suggest that hypometabolism of right sided brain regions involved in executive functioning, visuospatial processing, attention, and working memory underlie functional impairments in patients with AD. C1 [Melrose, Rebecca J.; Harwood, Dylan; Achamallah, Natalie; Campa, Olivia; Sultzer, David L.] VA Greater Los Angeles Healthcare Syst, Brain Behav & Aging Res Ctr, Los Angeles, CA 90073 USA. [Melrose, Rebecca J.; Harwood, Dylan; Sultzer, David L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Ettenhofer, Mark L.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. [Mandelkern, Mark] VA Greater Los Angeles Healthcare Syst, Nucl Med Serv, Los Angeles, CA 90073 USA. [Mandelkern, Mark] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Melrose, RJ (reprint author), VA Greater Los Angeles Healthcare Syst, Brain Behav & Aging Res Ctr, 11301 Wilshire Blvd,116AE, Los Angeles, CA 90073 USA. EM rjmelrose@ucla.edu FU Forest Research Institute; Department of Veterans Affairs; Office of RD; Office of Academic Affiliations; NIMH [R01MH56031] FX We thank Theresa Khoo for her assistance with formatting this manuscript. Dr Sultzer has received research grant support from Forest Research Institute. Potential conflicts to study participants were disclosed. None of the other authors report conflicts of interest.; The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: funded by the Department of Veterans Affairs (the Office of R&D, Merit Review, Career Development Award to R. Melrose; Office of Academic Affiliations, Special Fellowship Program in Advanced Geriatrics) and NIMH (R01MH56031). Study activities took place at the VA and the study was reviewed and approved by the VA and UCLA IRBs. It was presented in poster form at the American Association for Geriatric Psychiatry in Spring 2009. NR 70 TC 21 Z9 22 U1 4 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 EI 1552-5708 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SEP PY 2011 VL 24 IS 3 BP 127 EP 134 DI 10.1177/0891988711405333 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 809JS UT WOS:000294050600002 PM 21856969 ER PT J AU Teng, E Melrose, RJ Osato, S Jimenez, E Ercoli, LM Jarvik, LF AF Teng, Edmond Melrose, Rebecca J. Osato, Sheryl Jimenez, Elvira Ercoli, Linda M. Jarvik, Lissy F. TI Increasing Depressive Symptoms in Children of Alzheimer Parents SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE Alzheimer disease; offspring; longitudinal; depression ID MIDDLE-AGED CHILDREN; COGNITIVE DECLINE; RISK-FACTOR; RATING-SCALE; NEUROCOGNITIVE PERFORMANCE; HAMILTON DEPRESSION; FAMILY-HISTORY; OLDER-ADULTS; DISEASE; DEMENTIA AB Children of persons with Alzheimer disease (AD) are at increased risk of developing AD themselves, but specific factors that predict AD in this population have yet to be elucidated. Various studies indicate depressive symptoms may predate clinical AD and represent a risk factor and/or prodrome of incipient dementia, but their relevance for AD offspring remains uncertain. As part of a longitudinal family study of AD, we assessed depressive symptomatology in 30 middle aged AD offspring (mean age at baseline: 41.2). Their mean total scores on the Hamilton Depression Rating scale increased from 1.8 to 5.3 (P < .001) across a 20-year interval. Neurocognitive performance remained stable in a subset of this cohort (N = 25) over the same interval. Findings from this small convenience sample suggest emerging depressive symptoms may be among the earliest signs of subsequent dementia in this high-risk population but require confirmation through further longitudinal follow-up and replication in larger populations. C1 [Teng, Edmond; Melrose, Rebecca J.; Osato, Sheryl; Jimenez, Elvira; Jarvik, Lissy F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Teng, Edmond; Jimenez, Elvira] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Melrose, Rebecca J.; Osato, Sheryl; Jimenez, Elvira; Ercoli, Linda M.; Jarvik, Lissy F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Ercoli, Linda M.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. RP Teng, E (reprint author), W Los Angeles VA Healthcare Ctr, Neurobehav Unit, Bldg 401 116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eteng@ucla.edu FU Albert Parvin Foundation; Lon V. Smith Foundation; NIA [K08 AG34628]; AFAR; John A. Hartford Foundation; Atlantic Philanthropies, Starr Foundation FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Albert Parvin Foundation and the Lon V. Smith Foundation. ET is also supported by K08 AG34628 (jointly sponsored by the NIA, AFAR, John A. Hartford Foundation, Atlantic Philanthropies, Starr Foundation, and an anonymous donor). NR 59 TC 0 Z9 0 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SEP PY 2011 VL 24 IS 3 BP 135 EP 141 DI 10.1177/0891988711409402 PG 7 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 809JS UT WOS:000294050600003 PM 21633123 ER PT J AU Xu, J Lai, KKY Verlinsky, A Lugea, A French, SW Cooper, MP Ji, C Tsukamoto, H AF Xu, Jun Lai, Keane K. Y. Verlinsky, Alla Lugea, Aurelia French, Samuel W. Cooper, Marcus P. Ji, Cheng Tsukamoto, Hidekazu TI Synergistic steatohepatitis by moderate obesity and alcohol in mice despite increased adiponectin and p-AMPK SO JOURNAL OF HEPATOLOGY LA English DT Article DE Synergistic steatohepatitis; Obesity and alcohol synergism; Apoptosis; Necrosis; Macrophage activation; Nitrosative stress ID ENDOPLASMIC-RETICULUM STRESS; INDUCED INSULIN-RESISTANCE; FATTY LIVER-DISEASES; NITRIC-OXIDE; ER STRESS; MITOCHONDRIAL DYSFUNCTION; HEPATIC STEATOSIS; OXIDATIVE STRESS; UNITED-STATES; IN-VIVO AB Background & Aims: Mechanisms underlying synergistic liver injury caused by alcohol and obesity are not clear. We have produced a mouse model of synergistic steatohepatitis by recapitulating the natural history of the synergism seen in patients for mechanistic studies. Methods: Moderate obesity was induced in mice by 170% overnutrition in calories using intragastric overfeeding of high fat diet. Alcohol (low or high dose) was then co-administrated to determine its effects. Results: Moderate obesity plus alcohol intake causes synergistic steatohepatitis in an alcohol dose-dependent manner. A heightened synergism is observed when a high alcohol dose (32 g/kg/d) is used, resulting in plasma ALT reaching 392 +/- 28 U/L, severe steatohepatitis with pericellular fibrosis, marked M1 macrophage activation, a 40-fold induction of iNos, and intensified nitrosative stress in the liver. Hepatic expression of genes for mitochondrial biogenesis and metabolism are significantly downregulated, and hepatic ATP level is decreased. Synergistic ER stress evident by elevated XBP-1, GRP78 and CHOP is accompanied by hyperhomocysteinemia. Despite increased caspase 3/7 cleavage, their activities are decreased in a redox-dependent manner. Neither increased PARP cleavage nor TUNEL positive hepatocytes are found, suggesting a shift of apoptosis to necrosis. Surprisingly, the synergism mice have increased plasma adiponectin and hepatic p-AMPK, but adiponectin resistance is shown downstream of p-AMPK. Conclusions: Nitrosative stress mediated by M1 macrophage activation, adiponectin resistance, and accentuated ER and mitochondrial stress underlie potential mechanisms for synergistic steatohepatitis caused by moderate obesity and alcohol. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Xu, Jun; Lai, Keane K. Y.; Verlinsky, Alla; Lugea, Aurelia; French, Samuel W.; Tsukamoto, Hidekazu] Univ So Calif, Keck Sch Med, Dept Pathol, So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA 90089 USA. [Lugea, Aurelia; Tsukamoto, Hidekazu] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [French, Samuel W.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Cooper, Marcus P.] Univ Massachusetts, Sch Med, Div Cardiovasc Med, Worcester, MA USA. [Ji, Cheng] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90089 USA. RP Xu, J (reprint author), Univ So Calif, Keck Sch Med, Dept Pathol, So Calif Res Ctr ALPD & Cirrhosis, 1333 San Pablo St,MMR 428, Los Angeles, CA 90089 USA. EM junx@usc.edu FU NIH (Southern California Research Center for ALPD and Cirrhosis, Animal Core, and Morphology Core) [P50AA011999, R24AA012885, 2R01AA014428-06A1]; Medical Research Service of Department of Veterans Affairs; Suntory Holdings, Inc.; NIAAA [T32AA007578] FX The authors thank Hasmik Mkrtchyan, Akiko Ueno, and Hongyun She for their outstanding technical support. The present study was supported by NIH Grants, P50AA011999 (Southern California Research Center for ALPD and Cirrhosis, Animal Core, and Morphology Core), R24AA012885 (Non-Parenchymal Liver Cell Core), 2R01AA014428-06A1 (to C. Ji), Medical Research Service of Department of Veterans Affairs, and Suntory Holdings, Inc. Jun Xu and Keane Lai are both supported by the NIAAA Institutional Training grant (T32AA007578). NR 51 TC 51 Z9 51 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD SEP PY 2011 VL 55 IS 3 BP 673 EP 682 DI 10.1016/j.jhep.2010.12.034 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 807VH UT WOS:000293930600024 PM 21256905 ER PT J AU McDonald, CC Wiebe, DJ Guerra, T Thomas, N Richmond, TS AF McDonald, C. C. Wiebe, D. J. Guerra, T. Thomas, N. Richmond, T. S. TI The importance of family to youth living in violent communities SO JOURNAL OF PSYCHIATRIC AND MENTAL HEALTH NURSING LA English DT Article ID EXPOSURE C1 [McDonald, C. C.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia Collaborat Violence Prevent Ctr, Philadelphia, PA 19104 USA. [Wiebe, D. J.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia Collaborat Violence Prevent Ctr, Philadelphia, PA 19104 USA. [Richmond, T. S.] Univ Penn, Sch Nursing, Dept Biobehav & Hlth Sci, Philadelphia Collaborat Violence Prevent Ctr, Philadelphia, PA 19104 USA. RP McDonald, CC (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia Collaborat Violence Prevent Ctr, Philadelphia, PA 19104 USA. FU Centers for Disease Control and Prevention [5 U49 CE001093]; National Institute of Nursing Research [F31NR011107] FX This manuscript was supported by the cooperative agreement number 5 U49 CE001093 from The Centers for Disease Control and Prevention. Its contents are the sole responsibility of the authors and do not represent the official position of the Centers for Disease Control and Prevention. This research was also supported by Award Number F31NR011107 (PI: Catherine C. McDonald) from the National Institute of Nursing Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Nursing Research or the National Institutes of Health. NR 10 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-0126 J9 J PSYCHIATR MENT HLT JI J. Psychiatr. Ment. Health Nurs. PD SEP PY 2011 VL 18 IS 7 BP 653 EP 656 DI 10.1111/j.1365-2850.2011.01774.x PG 4 WC Nursing; Psychiatry SC Nursing; Psychiatry GA 808WG UT WOS:000294011900014 PM 21848601 ER PT J AU Zeitlin, SI AF Zeitlin, Scott I. TI Is Prostatitis a Vascular Disease? SO JOURNAL OF UROLOGY LA English DT Editorial Material ID PELVIC PAIN SYNDROME; MEN C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. RP Zeitlin, SI (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. NR 11 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2011 VL 186 IS 3 BP 781 EP 782 DI 10.1016/j.juro.2011.06.011 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 804XL UT WOS:000293688300003 PM 21788041 ER PT J AU Chen, JL Hartono, JR John, R Bennett, M Zhou, XJ Wang, YX Wu, QQ Winterberg, PD Nagami, GT Lu, CY AF Chen, Jianlin Hartono, John R. John, Reji Bennett, Michael Zhou, Xin Jin Wang, Yanxia Wu, Qingqing Winterberg, Pamela D. Nagami, Glenn T. Lu, Christopher Y. TI Early interleukin 6 production by leukocytes during ischemic acute kidney injury is regulated by TLR4 SO KIDNEY INTERNATIONAL LA English DT Article DE acute kidney injury; acute renal failure; inflammation; ischemia-reperfusion; ischemic renal failure ID ACUTE-RENAL-FAILURE; TOLL-LIKE RECEPTOR-2; GROUP BOX-1 PROTEIN; REPERFUSION INJURY; INFLAMMATORY RESPONSE; C57BL/10SCCR MICE; IN-VIVO; ISCHEMIA/REPERFUSION INJURY; EPITHELIAL-CELLS; GENE-EXPRESSION AB Although leukocytes infiltrate the kidney during ischemic acute kidney injury (AKI) and release interleukin 6 (IL6), their mechanism of activation is unknown. Here, we tested whether Toll-like receptor 4 (TLR4) on leukocytes mediated this activation by interacting with high-mobility group protein B1 (HMGB1) released by renal cells as a consequence of ischemic kidney injury. We constructed radiation-induced bone marrow chimeras using C3H/HeJ and C57BL/10ScNJ strains of TLR4 (-/-) mice and their respective TLR4 (+/+) wild-type counterparts and studied them at 4 h after an ischemic insult. Leukocytes adopted from TLR4 (+/+) mice infiltrated the kidneys of TLR4 (-/-) mice, and TLR4 (-/-) leukocytes infiltrated the kidneys of TLR4 (+/+) mice but caused little functional renal impairment in each case. Maximal ischemic AKI required both radiosensitive leukocytes and radioresistant renal parenchymal and endothelial cells from TLR4 (+/+) mice. Only TLR4 (+/+) leukocytes produced IL6 in vivo and in response to HMGB1 in vitro. Thus, following infiltration of the injured kidney, leukocytes produce IL6 when their TLR4 receptors interact with HMGB1 released by injured renal cells. This underscores the importance of TLR4 in the pathogenesis of ischemic AKI. Kidney International (2011) 80, 504-515; doi:10.1038/ki.2011.140; published online 1 June 2011 C1 [Chen, Jianlin; Hartono, John R.; John, Reji; Wang, Yanxia; Wu, Qingqing; Lu, Christopher Y.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Nephrol, Dallas, TX 75390 USA. [Bennett, Michael; Zhou, Xin Jin] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Winterberg, Pamela D.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Lu, Christopher Y.] Univ Texas SW Med Ctr Dallas, Grad Program Immunol, Dallas, TX 75390 USA. [Nagami, Glenn T.] Vet Affairs Greater Los Angeles Healthcare Syst, Nephrol Sect, Med Serv, Los Angeles, CA USA. [Nagami, Glenn T.] Vet Affairs Greater Los Angeles Healthcare Syst, Nephrol Sect, Res Serv, Los Angeles, CA USA. RP Lu, CY (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Nephrol, Dallas, TX 75390 USA. EM christopher.lu@utsouthwestern.edu FU NIH [RO-1 DK069633, F32DK084701, T32DK07257]; Beecherl Foundation; NIH, UT Southwesterrn O'Brien Kidney Research Core Center [DK079328] FX This study was supported by NIH RO-1 DK069633 and a Beecherl Foundation Grant to CYL; NIH F32DK084701 and T32DK07257 to JRH; and the NIH DK079328 UT Southwesterrn O'Brien Kidney Research Core Center. We thank Thomas Carroll for the low-power photography and Kathy Trueman for assistance in preparing the manuscript and figures. NR 86 TC 27 Z9 31 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 SEP PY 2011 VL 80 IS 5 BP 504 EP 515 DI 10.1038/ki.2011.140 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 806UX UT WOS:000293840800012 PM 21633411 ER PT J AU Chang, A Chou, CL Teherani, A Hauer, KE AF Chang, Anna Chou, Calvin L. Teherani, Arianne Hauer, Karen E. TI Clinical skills-related learning goals of senior medical students after performance feedback SO MEDICAL EDUCATION LA English DT Article ID SELF-ASSESSMENT; REMEDIATION; EDUCATION; ACCURACY; MOTIVATION AB CONTEXT Lifelong learning is essential for doctors to maintain competence in clinical skills. With performance feedback, learners should be able to formulate specific and achievable learning goals in areas of need. OBJECTIVES We aimed to determine: (i) the type and specificity of medical student learning goals after a required clinical performance examination; (ii) differences in goal setting among low, average and high performers, and (iii) whether low performers articulate learning goals that are concordant with their learning needs. METHODS We conducted a single-site, multi-year, descriptive comparison study. Senior medical students were given performance benchmarks, individual feedback and guidelines on learning goals; each student was subsequently instructed to write two clinical skills learning goals. Investigators coded the learning goals for specificity, categorised the goals, and performed statistical analyses to determine their concordance with student performance level (low, average or high) in data gathering (history taking and physical examination) or communication skills. RESULTS All 208 students each wrote two learning goals and most (n = 200, 96%) wrote two specific learning goals. Nearly two-thirds of low performers in data gathering wrote at least one learning goal that referred to history taking or physical examination; one-third wrote learning goals pertaining to the organisation of the encounter. High performers in data gathering wrote significantly more patient education goals and significantly fewer history-taking goals than average or low performers. Only 50% of low performers in communication wrote learning goals related to communication skills. Low performers in communication were significantly more likely than average or high performers to identify learning goals related to improving performance in future examinations. CONCLUSIONS The provision of performance benchmarking, individual feedback and brief written guidelines helped most senior medical students in our study to write specific clinical skills learning goals. Many low-performing students did not write learning goals concordant with their areas of weakness. Future work might focus on enhancing low performers' continued learning in areas of performance deficits. C1 [Chang, Anna] Univ Calif San Francisco, Div Geriatr, Dept Med, Sch Med, San Francisco, CA 94121 USA. [Chang, Anna; Chou, Calvin L.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. RP Chang, A (reprint author), Univ Calif San Francisco, Div Geriatr, Dept Med, Sch Med, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM Anna.Chang2@va.gov NR 34 TC 10 Z9 11 U1 1 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0308-0110 J9 MED EDUC JI Med. Educ. PD SEP PY 2011 VL 45 IS 9 BP 878 EP 885 DI 10.1111/j.1365-2923.2011.04015.x PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 808XF UT WOS:000294014600005 PM 21848715 ER PT J AU Deshane, J Zmijewski, JW Luther, R Gaggar, A Deshane, R Lai, JF Xu, X Spell, M Estell, K Weaver, CT Abraham, E Schwiebert, LM Chaplin, DD AF Deshane, J. Zmijewski, J. W. Luther, R. Gaggar, A. Deshane, R. Lai, J-F Xu, X. Spell, M. Estell, K. Weaver, C. T. Abraham, E. Schwiebert, L. M. Chaplin, D. D. TI Free radical-producing myeloid-derived regulatory cells: potent activators and suppressors of lung inflammation and airway hyperresponsiveness SO MUCOSAL IMMUNOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; TUMOR-BEARING MICE; T-CELLS; ALVEOLAR MACROPHAGES; REACTIVE OXYGEN; MURINE MODEL; MILD ASTHMA; ARGINASE-I; SUPEROXIDE; INHIBITION AB Levels of reactive free radicals are elevated in the airway during asthmatic exacerbations, but their roles in the pathophysiology of asthma remain unclear. We have identified subsets of myeloid-derived suppressor-like cells as key sources of nitric oxide and superoxide in the lungs of mice with evolving experimental allergic airway inflammation and established these cells as master regulators of the airway inflammatory response. The profiles of free radicals they produced depended on expression of inducible nitric oxide synthase (iNOS), arginase, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. These radicals controlled the pro-and anti-inflammatory potential of these cells, and also regulated the reciprocal pattern of their infiltration into the lung. The nitric oxide-producing cells were Ly-6C(+)Ly-6G(-) and they downmodulated T-cell activation, recruited T(reg) cells, and dramatically downregulated antigen-induced airway hyperresponsiveness. The superoxide-producing cells were Ly-6C(-)Ly-6G(+) and they expressed proinflammatory activities, exacerbating airway hyperresponsiveness in a superoxide-dependent fashion. A smaller population of Ly-6C(+)Ly-6G(+) cells also suppressed T-cell responses, but in an iNOS- and arginase-independent fashion. These regulatory myeloid cells represent important targets for asthma therapy. C1 [Deshane, J.; Luther, R.; Deshane, R.; Lai, J-F; Chaplin, D. D.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Deshane, J.; Zmijewski, J. W.; Gaggar, A.; Xu, X.; Spell, M.; Abraham, E.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Deshane, J.; Zmijewski, J. W.; Abraham, E.; Schwiebert, L. M.; Chaplin, D. D.] Univ Alabama, Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Gaggar, A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Spell, M.] Univ Alabama, Ctr AIDS Res, Birmingham, AL 35294 USA. [Estell, K.; Schwiebert, L. M.] Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. [Weaver, C. T.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. [Chaplin, D. D.] Univ Alabama, Comprehens Arthrit Musculoskeletal & Autoimmun Ct, Birmingham, AL 35294 USA. RP Chaplin, DD (reprint author), Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. EM dchaplin@uab.edu OI Weaver, Casey/0000-0002-2180-1793; Chaplin, David/0000-0002-1354-3069 FU NIH [5T32HL007553, 5T32AI007051, 1F32HL095341, 5P01HL073907, 5R01HL075465, 5R01HL062221, 1R01GM087748, 2R01HL076206] FX We thank Meiqin Zeng for expert technical assistance and Kathy May for management of the animal colony used to support this work. We gratefully acknowledge Hubert Tse for providing p47m mice to carry out adoptive transfer experiments. We also acknowledge helpful comments from Jack Lancaster, Carlene Zindl, Kelly M. McNagny, and Jillian Wohler. Support for these studies was provided by the NIH grants 5T32HL007553 (J.D.), 5T32AI007051 (J.D.), 1F32HL095341 (J.D.), 5P01HL073907 (D.D.C.), 5R01HL075465 (L.M.S.), 5R01HL062221 (E.A.), 1R01GM087748 (E.A.), and 2R01HL076206 (E.A.). NR 54 TC 36 Z9 40 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD SEP PY 2011 VL 4 IS 5 BP 503 EP 518 DI 10.1038/mi.2011.16 PG 16 WC Immunology SC Immunology GA 809HC UT WOS:000294041400004 PM 21471960 ER PT J AU Radley, JJ Kabbaj, M Jacobson, L Heydendael, W Yehuda, R Herman, JP AF Radley, Jason J. Kabbaj, Mohamed Jacobson, Lauren Heydendael, Willem Yehuda, Rachel Herman, James P. TI Stress risk factors and stress-related pathology: Neuroplasticity, epigenetics and endophenotypes SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS LA English DT Review DE Antidepressants; post-traumatic stress disorder; depression; glucocorticoids; hippocampus; individual differences ID MEDIAL PREFRONTAL CORTEX; PITUITARY-ADRENOCORTICAL AXIS; NOVELTY-SEEKING BEHAVIOR; TRANSCRIPTIONAL COACTIVATORS P300; CORTICOTROPIN-RELEASING HORMONE; RECEPTOR GENE-EXPRESSION; MESSENGER-RNA LEVELS; MALE C57BL/6 MICE; MAJOR DEPRESSION; INDIVIDUAL-DIFFERENCES AB This paper highlights a symposium on stress risk factors and stress susceptibility, presented at the Neurobiology of Stress workshop in Boulder, CO, in June 2010. This symposium addressed factors linking stress plasticity and reactivity to stress pathology in animal models and in humans. Dr. J. Radley discussed studies demonstrating prefrontal cortical neuroplasticity and prefrontal control of hypothalamo-pituitary-adrenocortical axis function in rats, highlighting the emerging evidence of the critical role that this region plays in normal and pathological stress integration. Dr. M. Kabbaj summarized his studies of possible epigenetic mechanisms underlying behavioral differences in rat populations bred for differential stress reactivity. Dr. L. Jacobson described studies using a mouse model to explore the diverse actions of antidepressants in brain, suggesting mechanisms whereby antidepressants may be differentially effective in treating specific depression endophenotypes. Dr. R. Yehuda discussed the role of glucocorticoids in post-traumatic stress disorder (PTSD), indicating that low cortisol level may be a trait that predisposes the individual to development of the disorder. Furthermore, she presented evidence indicating that traumatic events can have transgenerational impact on cortisol reactivity and development of PTSD symptoms. Together, the symposium highlighted emerging themes regarding the role of brain reorganization, individual differences, and epigenetics in determining stress plasticity and pathology. C1 [Herman, James P.] Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45237 USA. [Radley, Jason J.] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. [Kabbaj, Mohamed] Florida State Univ, Dept Biomed Sci, Program Neurosci, Tallahassee, FL 32306 USA. [Jacobson, Lauren; Heydendael, Willem] Albany Med Coll, Ctr Neuropharmacol & Neurosci, Albany, NY 12208 USA. [Yehuda, Rachel] James J Peters VA Med Ctr, Bronx, NY USA. [Yehuda, Rachel] Mt Sinai Sch Med, Bronx, NY USA. RP Herman, JP (reprint author), Univ Cincinnati, Dept Psychiat, Psychiat N,Bldg E,2nd Floor,2170 E Galbraith Rd, Cincinnati, OH 45237 USA. EM james.herman@uc.edu RI Kabbaj, Mohamed/M-9240-2016; Herman, James/D-4960-2015 OI Herman, James/0000-0003-3571-2406 FU NIH [R13MH090623, R01MH087583, R21MH081046, R21MH 083128, R01MH080394]; NARSAD; Anxiety Disorders Association of America; VISN3 MIRECC, DOD [W81XWH-06-2-0032]; NIH ARRA [RC1MH088101]; Lightfighter Trust FX The 2010 Neurobiology of Stress Workshop was supported by NIH grant R13MH090623 (JPH). Research reported in this review was supported by NARSAD and Anxiety Disorders Association of America Young Investigator Awards (JJR); NIH grants R01MH087583, R21MH081046, and R21MH 083128 (MK); NIH grant R01MH080394 (LJ); and VISN3 MIRECC, DOD award # W81XWH-06-2-0032, NIH ARRA grant RC1MH088101, and the Lightfighter Trust (RY). NR 147 TC 43 Z9 46 U1 7 U2 40 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1025-3890 J9 STRESS JI Stress PD SEP PY 2011 VL 14 IS 5 BP 481 EP 497 DI 10.3109/10253890.2011.604751 PG 17 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology GA 808VC UT WOS:000294008400004 PM 21848436 ER PT J AU Dransfield, MT Cockcroft, JR Townsend, RR Coxson, HO Sharma, SS Rubin, DB Emmett, AH Cicale, MJ Crater, GD Martinez, FJ AF Dransfield, Mark T. Cockcroft, John R. Townsend, Raymond R. Coxson, Harvey O. Sharma, Sanjay S. Rubin, David B. Emmett, Amanda H. Cicale, Michael J. Crater, Glenn D. Martinez, Fernando J. TI Effect of fluticasone propionate/salmeterol on arterial stiffness in patients with COPD SO RESPIRATORY MEDICINE LA English DT Article DE Augmentation index; Computed tomography scanning; Emphysema; Aortic pulse wave velocity ID OBSTRUCTIVE PULMONARY-DISEASE; PULSE-WAVE VELOCITY; LUNG-FUNCTION; CARDIOVASCULAR EVENTS; AUGMENTATION INDEX; RISK; INFLAMMATION; EMPHYSEMA; CORTICOSTEROIDS; MORTALITY AB Background: COPD is associated with increased arterial stiffness which may in part explain the cardiovascular morbidity observed in the disease. A causal relationship between arterial stiffness and cardiovascular events has not been established, though their strong association raises the possibility that therapies that reduce arterial stiffness may improve cardiovascular outcomes. Prior studies suggest that fluticasone propionate/salmeterol (FSC) may improve cardiovascular outcomes in COPD and we hypothesized that FSC would reduce arterial stiffness in these patients. Methods: This multicenter, randomized, double-blind, placebo-controlled study compared the effects of FSC 250/50 mu g twice-daily and placebo on aortic pulse wave velocity (aPWV) as determined by ECG-gated carotid and femoral artery waveforms. The primary endpoint was aPWV change from baseline at 12-weeks (last measure for each patient). Results: 249 patients were randomized; the mean FEV(1) in each group was similar (55% predicted) and 60% of patients reported a cardiovascular disorder. At 12-weeks, aPWV between FSC and placebo was -0.42 m/s (95%CI -0.88, 0.03; p = 0.065). A statistically significant reduction in aPWV between FSC and placebo was observed in those who remained on study drug throughout the treatment period [-0.49 m/s (95%CI 0.98, -0.01; p = 0.045)]. A post hoc analysis suggested the effect of FSC was greater in patients with higher baseline aPWV. Conclusion: FSC does not reduce aPWV in all patients with moderate to severe COPD, but may have effects in those with elevated arterial stiffness. Additional studies are required to determine if aPWV could serve as a surrogate for cardiovascular events in COPD. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Dransfield, Mark T.] Univ Alabama, Univ Alabama Birmingham Lung Hlth Ctr, Birmingham VA Med Ctr, Birmingham, AL USA. [Cockcroft, John R.] Univ Hosp, Wales Heart Res Inst, Dept Cardiol, Cardiff CF14 4XN, S Glam, Wales. [Townsend, Raymond R.] Univ Penn, Sch Med, Dept Med, Hypertens Program, Philadelphia, PA 19104 USA. [Coxson, Harvey O.] Univ British Columbia, Vancouver Gen Hosp, Dept Radiol, Vancouver, BC V5Z 1M9, Canada. [Coxson, Harvey O.] Univ British Columbia, Vancouver Gen Hosp, UBC James Hogg Res Ctr, Vancouver, BC V5Z 1M9, Canada. [Sharma, Sanjay S.; Rubin, David B.; Emmett, Amanda H.; Cicale, Michael J.; Crater, Glenn D.] GlaxoSmithKline Inc, Resp & Immunoinflammat Med Dev Ctr, Res Triangle Pk, NC USA. [Martinez, Fernando J.] Univ Michigan Hlth Syst, Div Pulm & Crit Care Med, Ann Arbor, MI USA. RP Dransfield, MT (reprint author), Univ Alabama, Univ Alabama Birmingham Lung Hlth Ctr, Birmingham VA Med Ctr, Birmingham, AL USA. EM mdransfield99@msn.com RI Coxson, Harvey/A-9861-2017 OI Coxson, Harvey/0000-0001-5750-9711; Crater, Glenn/0000-0002-1159-1323 FU GlaxoSmithKline, Research Triangle Park, NC [NCT00857766]; NHLBI; Aeris; Altana/Nycomed/Forest; AstraZeneca; Boehringer Ingelheim; Novartis; Pfizer; Roche; UpToDate; Associates in Medical Marketin; Castle Connolly FX This study (NCT00857766) was funded by GlaxoSmithKline, Research Triangle Park, NC. All authors were involved with the initial concept of the paper, were extensively involved with the writing, and retained full editorial control throughout the development of the manuscript. Final approval was solely endorsed by the authors. All authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. The authors did not receive any money for writing the manuscript. MTD has received COPD-related research funding from the NHLBI as well as Aeris, Altana/Nycomed/Forest, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Pfizer, and Roche. He has served on an advisory board for GSK and BI and has received speakers' honoraria from GSK and BI for COPD-related talks. JRC is a PI for the ARCADE Study and a member of GSK advisory board for GSK UK. RRT serves as a consultant to GlaxoSmithKline, Merck and Novartis and receives royalties from UpToDate. HOC has received an honorarium for serving on the steering committee for the ECLIPSE project for GSK. In addition he was the co-investigator on two multi-center studies sponsored by GSK and has received travel expenses to attend meetings related to the project. He has a contract service agreement with GSK to quantify the CT scans in subjects with COPD and a service agreement with Spiration Inc to measure changes in lung volume in subjects with severe emphysema. He has received a fee for speaking at a conference and related travel expenses from AstraZeneca (Australia). FJM has served on Advisory Boards relating to COPD related topics for GSK, MedImmune/AstraZeneca, Ikaria, Merck, Pearl, Novartis, UBC, Forest/Almirall. He has consulted for Boehringer Ingelheim, Nycomed/Forest, Roche, Bayer, Schering, HLS, Talecris, Comgenix, fb Communications, Boom Comm and Actelion. He has served on Speaker's Bureaus for GSK, NACE, Med Ed, Potomac, Pfizer, Boehringer Ingelheim, Schering, Vox Medic, American Lung Association, WebMD, ePocrates, AstraZeneca, France Foundation and Altana /Nycomed. His institution has received funds from Boehringer Ingelheim for a clinical trial. He has received royalties from Associates in Medical Marketin and Castle Connolly. He has developed educational materials for the France Foudation, HIT Global and ePocrates. He has served on Steering Committees for clinical trials supported by GSK, Nycomed, and Actelion. MJC was an employee of GlaxoSmithKline at the time the manuscript was written. SSS, GDC, DBR, and AHE are all employees of GlaxoSmithKline and own stock in the company. NR 34 TC 16 Z9 16 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD SEP PY 2011 VL 105 IS 9 BP 1322 EP 1330 DI 10.1016/j.rmed.2011.05.016 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 805JX UT WOS:000293723800009 PM 21696934 ER PT J AU Yehuda, R AF Yehuda, Rachel TI Are Different Biological Mechanisms Involved in the Transmission of Maternal Versus Paternal Stress-Induced Vulnerability to Offspring? SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID HOLOCAUST SURVIVORS; EXPOSURE C1 [Yehuda, Rachel] Mt Sinai Sch Med, James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Yehuda, Rachel] Mt Sinai Sch Med, Traumat Stress Studies Div, Dept Psychiat, Bronx, NY 10468 USA. RP Yehuda, R (reprint author), Mt Sinai Sch Med, James J Peters Vet Affairs Med Ctr, 526 OOMH PTSD 116-A,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM rachel.yehuda@va.gov FU NIMH NIH HHS [5RC1MH088101-02] NR 11 TC 7 Z9 7 U1 0 U2 10 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 SEP 1 PY 2011 VL 70 IS 5 BP 402 EP 403 DI 10.1016/j.biopsych.2011.07.001 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 803JE UT WOS:000293576800007 PM 21820529 ER PT J AU Brasky, TM Lampe, JW Slatore, CG White, E AF Brasky, Theodore M. Lampe, Johanna W. Slatore, Christopher G. White, Emily TI Use of glucosamine and chondroitin and lung cancer risk in the VITamins And Lifestyle (VITAL) cohort SO CANCER CAUSES & CONTROL LA English DT Article DE Adenocarcinoma; Chondroitin; Glucosamine; Non-small-cell lung cancer; Small-cell lung cancer; Supplement ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LOW-DOSE ASPIRIN; KNEE OSTEOARTHRITIS; WOMENS HEALTH; SULFATE; CHEMOPREVENTION; RECOMMENDATIONS; INFLAMMATION; METAANALYSIS; SUPPLEMENTS AB Inflammation plays an important role in lung carcinogenesis. Epidemiologic studies have reported inverse associations of non-steroidal anti-inflammatory drug (NSAID) use and lung cancer risk. Previously, we found that ever use of glucosamine and chondroitin, which have anti-inflammatory properties, were inversely associated with lung cancer risk. After an additional year of follow-up, we further examined the association including frequency/duration of use, interaction with factors associated with inflammation, and lung cancer histology. Participants were members of the VITamins And Lifestyle cohort. Adults, aged 50-76 years, who were residents of western Washington State, completed a baseline questionnaire in 2000-2002 (n = 76,904). Participants were queried on their use of glucosamine and chondroitin, over the 10 years prior to baseline, and categorized as nonuser, low use < 4 days/week or < 3 years, or high use a parts per thousand yen4 days/week and a parts per thousand yen3 years. Lung cancer cases (n = 808) were ascertained through linkage to the Surveillance, Epidemiology, and End Results cancer registry. High 10-year use of glucosamine [hazard ratio (HR), 0.77; 95% CI: 0.56-1.07; p trend = 0.04] but not chondroitin was associated with a reduction in lung cancer risk. The association with glucosamine was limited to adenocarcinoma (HR, 0.49; 95% CI: 0.27-0.90; p trend < 0.01) and was not modified by NSAID use or smoking status. Our results for glucosamine use are similar to the prior human studies of NSAID use and lung cancer, both in magnitude and the limitation of the association to adenocarcinoma. Unlike NSAIDs, glucosamine has no known adverse effects. Although confirmatory studies are needed, glucosamine is an attractive candidate for lung cancer chemoprevention. C1 [Brasky, Theodore M.; Lampe, Johanna W.; White, Emily] Fred Hutchinson Canc Res Ctr, Canc Prevent Unit, Seattle, WA 98109 USA. [Brasky, Theodore M.; Lampe, Johanna W.; White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Slatore, Christopher G.] Portland VA Med Ctr, Portland, OR USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Dept Pulm & Crit Care Med, Portland, OR 97201 USA. RP Brasky, TM (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Unit, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM tbrasky@fhcrc.org OI Slatore, Christopher/0000-0003-0958-8122 FU National Institutes of Health, National Cancer Institute [R25-CA94880, R01-CA142545, K05-CA154337] FX This work is supported in part by grants R25-CA94880, R01-CA142545, and K05-CA154337 from the National Institutes of Health, National Cancer Institute. Dr. Slatore's work on this project was supported with resources and the use of facilities at the Portland VA Medical Center. NR 39 TC 8 Z9 9 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 2011 VL 22 IS 9 BP 1333 EP 1342 DI 10.1007/s10552-011-9806-8 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 799OO UT WOS:000293296200011 PM 21706174 ER PT J AU Guthrie, CR Kraemer, BC AF Guthrie, Chris R. Kraemer, Brian C. TI Proteasome Inhibition Drives HDAC6-Dependent Recruitment of Tau to Aggresomes SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE HDAC6; Aggresome; Tau; Protein aggregation; Proteasome; Tauopathy ID HELICAL FILAMENT-TAU; ALZHEIMERS-DISEASE; AUTOPHAGIC DEGRADATION; PHOSPHORYLATED TAU; FTDP-17 MUTATIONS; AGGREGATION; PROTEIN; TAUOPATHY; CELLS; MODEL AB Lesions containing aggregated and hyperphosphorylated tau protein are characteristic of neurodegenerative tauopathies. We have developed a cellular model of pathological tau deposition and clearance by overexpressing wild type human tau in HEK293 cells. When proteasome activity is inhibited, HEK293/tau cells accumulate tau protein in structures that bear many of the hallmarks of aggresomes. These include recruitment of tau into large spherical inclusions, accumulation of the retrograde motor protein dynein at the centrosome, formation of an intermediate filament cage around inclusions, and clustering of mitochondria at the aggresome. Tau aggresomes form rapidly and can be cleared upon relief of proteasome inhibition. We observe recruitment of pathological misfolded phospho-tau species to aggresomes. Immunoblotting reveals accumulation of detergent insoluble aggregated tau species. Knockdown of histone deacetylase 6, a protein known to interact with tau, reveals a requirement for HDAC6 activity in tau aggresome formation. Direct observation of the accumulation and clearance of abnormal tau species will allow us to dissect the cellular and molecular mechanisms at work in clearing aggresomal tau and its similarity to disease relevant pathological tau clearance mechanisms. C1 [Kraemer, Brian C.] Seattle Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Guthrie, Chris R.; Kraemer, Brian C.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Kraemer, Brian C.] Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98104 USA. RP Kraemer, BC (reprint author), Seattle Vet Affairs Puget Sound Hlth Care Syst, S182 1660 S Columbian Way, Seattle, WA 98108 USA. EM kraemerb@uw.edu FU Department of Veterans Affairs; National Institute of Neurological Disorders and Stroke [R01 NS064131] FX This work was supported by a Department of Veterans Affairs Merit Review Grant (B. C. K.) and by National Institute of Neurological Disorders and Stroke Grant R01 NS064131 (B. C. K.) We thank Pam McMillan for critical reading of the manuscript. We thank the anonymous reviewers for their critical reviews and advice which helped improve this manuscript. We thank Elaine Loomis and Susan Danner for outstanding technical assistance. We thank Peter Davies, Virginia Lee, and Peter Seubert for tau antibodies and the Developmental Studies Hybridoma Bank (NICHD) for the beta-tubulin antibody E7. NR 43 TC 18 Z9 20 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD SEP PY 2011 VL 45 IS 1 BP 32 EP 41 DI 10.1007/s12031-011-9502-x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 798GT UT WOS:000293191300005 PM 21340680 ER PT J AU Gros, DF AF Gros, Daniel F. TI Startle Inhibition to Positive-Activated Compared to Neutral Stimuli: Variations in Self-Reported Behavioral Approach SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Inhibition; Startle reflex; Behavioral approach system; Drive; Depression ID FEAR-POTENTIATED STARTLE; AFFECTIVE MODULATION; BIS/BAS SCALES; EMOTION; DEPRESSION; REFLEX; PUNISHMENT; RESPONSES; DISORDER; SYSTEMS AB In contrast to the research on potentiation of startle during negative emotional states, limited research has focused on the influence of individual differences in reward sensitivity on inhibition of startle during positive-activated emotional states. The present study attempted to replicate and extend previous research by investigating the influence of behavioral approach system (BAS) on the inhibition of startle. Based on a pre-screening of 3,000 participants, 76 undergraduates were recruited for low, moderate, and high BAS groups. Participants viewed a series of positive-activated, neutral, and negative-activated pictures, and bilateral startle eyeblink magnitude was recorded. Inhibition of startle was demonstrated across the entire sample; however, these findings appeared to be driven by participants in the high BAS group. Further, the Group x Affect interaction only was demonstrated in one BAS subscale (BAS-Drive) and the total BAS scale, suggesting differences among the subtypes of BAS in the processing of affective materials. C1 [Gros, Daniel F.] Ralph H Johnson VA Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Gros, Daniel F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Gros, DF (reprint author), Ralph H Johnson VA Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu NR 43 TC 3 Z9 3 U1 3 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD SEP PY 2011 VL 33 IS 3 BP 308 EP 314 DI 10.1007/s10862-011-9240-y PG 7 WC Psychology, Clinical SC Psychology GA 797PF UT WOS:000293139100002 ER PT J AU Wheaton, MG Braddock, AE Abramowitz, JS AF Wheaton, Michael G. Braddock, Autumn E. Abramowitz, Jonathan S. TI The Sweating Cognitions Inventory: A Measure of Cognitions in Hyperhidrosis SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Excessive sweating; Hyperhidrosis; Social anxiety; Anxiety sensitivity ID ILLNESS INTRUSIVENESS; RATING-SCALE; ANXIETY; INDIVIDUALS; VALIDATION; ACTIVATION; STABILITY; QUALITY; RETAIN; SAMPLE AB Primary hyperhidrosis is a dermatological condition involving excessive sweating. Little research has been conducted on the psychological processes associated with this condition. A cognitive-behavioral approach would suggest that negative beliefs about the nature and consequences of sweating paradoxically increase sweating, and therefore maintain hyperhidrosis. The present research reports on the development and psychometric evaluation of the Sweating Cognitions Inventory (SCI), a self-report measure that assesses dysfunctional beliefs in hyperhidrosis. The SCI was administered to a clinical sample of patients diagnosed with hyperhidrosis (N = 226) as well as a student comparison group (N = 482). The SCI demonstrated good internal consistency and a stable, unidimensional factor structure in both samples. Sweating cognitions differentiated between the two groups, indicating discriminant validity. Correlations with comparison measures indicated that sweating cognitions were strongly related to sweating severity, and also to social anxiety and anxiety sensitivity. These results are consistent with our conceptualization that dysfunctional sweating cognitions can maintain and exacerbate excessive sweating. A cognitive-behavioral conceptualization of hyperhidrosis could advance our understanding of the condition and could lead to novel treatment approaches. C1 [Wheaton, Michael G.; Abramowitz, Jonathan S.] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. [Braddock, Autumn E.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Abramowitz, JS (reprint author), Univ N Carolina, Dept Psychol, Campus Box 3270,Davie Hall, Chapel Hill, NC 27599 USA. EM mwheaton@email.unc.edu; autumn.braddock@va.gov; jabramowitz@unc.edu OI Wheaton, Michael/0000-0002-7465-7879 NR 38 TC 1 Z9 1 U1 3 U2 12 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD SEP PY 2011 VL 33 IS 3 BP 393 EP 402 DI 10.1007/s10862-010-9211-8 PG 10 WC Psychology, Clinical SC Psychology GA 797PF UT WOS:000293139100011 ER PT J AU Pickett, BE Striker, R Lefkowitz, EJ AF Pickett, B. E. Striker, R. Lefkowitz, E. J. TI Evidence for separation of HCV subtype 1a into two distinct clades SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE bioinformatics; drug resistance; hepatitis C virus; phylogeny; selection pressure ID HEPATITIS-C VIRUS; OPEN-READING FRAME; MULTIPLE SEQUENCE ALIGNMENT; HYPERVARIABLE REGION 1; RIBOSOME ENTRY SITE; PHYLOGENETIC ANALYSIS; RESISTANCE MUTATIONS; POSITIVE SELECTION; HYPERIMMUNE SERUM; PLUS RIBAVIRIN AB The nucleotide sequence diversity present among hepatitis C virus (HCV) isolates allows rapid adjustment to exterior forces including host immunity and drug therapy. This viral response reflects a combination of a high rate of replication together with an error-prone RNA-dependent RNA polymerase, providing for the selection and proliferation of the viruses with the highest fitness. We examined HCV subtype 1a whole-genome sequences to identify positions contributing to genotypic and phenotypic diversity. Phylogenetic tree reconstructions showed two distinct clades existing within the 1a subtype with each clade having a starlike tree topology and lacking definite correlation between time or place of isolation and phylogeny. Identification of significant phylogenetically informative sites at the nucleotide level revealed positions not only contributing to clade differentiation, but which are located at or proximal to codons associated with resistance to protease inhibitors (NS3 Q41) or polymerase inhibitors (NS5B S368). Synonymous/nonsynonymous substitution mutation analyses revealed that the majority of nucleotide mutations yielded synonymous amino acids, indicating the presence of purifying selection pressure across the polyprotein with pockets of positive selection also being detected. Despite evidence for divergence at several loci, certain 1a characteristics were preserved including the length of the alternative reading frame/F protein (ARF/F) gene, and a subtype 1a-specific phosphorylation site in NS5A (S349). Our analysis suggests that there may be strain-specific differences in the development of antiviral resistance to viruses infecting patients who are dependent on the genetic variation separating these two clades. C1 [Pickett, B. E.; Lefkowitz, E. J.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Striker, R.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Striker, R.] Univ Wisconsin, Dept Med, Madison, WI USA. [Striker, R.] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. RP Lefkowitz, EJ (reprint author), BBRB 276-11,1530 3rd Ave S, Birmingham, AL 35294 USA. EM elliotl@uab.edu OI Lefkowitz, Elliot/0000-0002-4748-4925 FU PHS [5 T32 AI007150-29]; NIH/NIAID [HHSN266200400036C]; American Cancer Society; Veteran's Administration [5I01CX000117-02]; University of Wisconsin Institute for Clinical and Translational Research; NIH [1UL1RR025011]; Public Health Service [5 T32 AI007150-29] FX We wish to thank Dr John Tavis and the Virahep-C study group for providing the drug resistance data and Dr. Cecile Ane for statistical help and critical reading of the manuscript. This work was supported by PHS Training grant 5 T32 AI007150-29 to BP and NIH/NIAID contract number HHSN266200400036C to EJL. RS is supported by the American Cancer Society, a Veteran's Administration Merit Award (5I01CX000117-02) and in part by the University of Wisconsin Institute for Clinical and Translational Research and funded through an NIH Clinical and Translational Science Award (CTSA), grant number 1UL1RR025011.; This study was funded (in part or in full) by: National Institutes of Health/National Institute for Allergies and Infectious Diseases, contract number HHSN266200400036C; Public Health Service, grant number 5 T32 AI007150-29; and National Institutes of Health, grant number 1UL1RR025011. NR 55 TC 37 Z9 37 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD SEP PY 2011 VL 18 IS 9 BP 608 EP 618 DI 10.1111/j.1365-2893.2010.01342.x PG 11 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 798GV UT WOS:000293191500002 PM 20565573 ER PT J AU Teng, E Kepe, V Frautschy, SA Liu, J Satyamurthy, N Yang, FS Chen, PP Cole, GB Jones, MR Huang, SC Flood, DG Trusko, SP Small, GW Cole, GM Barrio, JR AF Teng, Edmond Kepe, Vladimir Frautschy, Sally A. Liu, Jie Satyamurthy, Nagichettiar Yang, Fusheng Chen, Ping-Ping Cole, Graham B. Jones, Mychica R. Huang, Sung-Cheng Flood, Dorothy G. Trusko, Stephen P. Small, Gary W. Cole, Gregory M. Barrio, Jorge R. TI [F-18]FDDNP microPET imaging correlates with brain A beta burden in a transgenic rat model of Alzheimer disease: Effects of aging, in vivo blockade, and anti-A beta antibody treatment SO NEUROBIOLOGY OF DISEASE LA English DT Article DE [F-18]FDDNP; Positron emission tomography; Amyloid; Transgenic rat; Naproxen; Immunotherapy ID POSITRON-EMISSION-TOMOGRAPHY; PITTSBURGH COMPOUND-B; MILD COGNITIVE IMPAIRMENT; AMYLOID-BETA; MOUSE MODEL; PET; PLAQUES; PATHOLOGY; DEPOSITION; CLEARANCE AB In vivo detection of Alzheimer's disease (AD) neuropathology in living patients using positron emission tomography (PET) in conjunction with high affinity molecular imaging probes for beta-amyloid (A beta) and tau has the potential to assist with early diagnosis, evaluation of disease progression, and assessment of therapeutic interventions. Animal models of AD are valuable for exploring the in vivo binding of these probes, particularly their selectivity for specific neuropathologies, but prior PET experiments in transgenic mice have yielded conflicting results. In this work, we utilized microPET imaging in a transgenic rat model of brain A beta deposition to assess [F-18]FDDNP binding profiles in relation to age-associated accumulation of neuropathology. Cross-sectional and longitudinal imaging demonstrated that [F-18[FDDNP binding in the hippocampus and frontal cortex progressively increases from 9 to 18 months of age and parallels age-associated A beta accumulation. Specificity of in vivo [F-18]FDDNP binding was assessed by naproxen pretreatment, which reversibly blocked [F-18]FDDNP binding to A beta aggregrates. Both [F-18]FDDNP microPET imaging and neuropathological analyses revealed decreased A beta burden after intracranial anti-A beta antibody administration. The combination of this non-invasive imaging method and robust animal model of brain A beta accumulation allows for future longitudinal in vivo assessments of potential therapeutics for AD that target A beta production, aggregation, and/or clearance. These results corroborate previous analyses of [F-18]FDDNP PET imaging in clinical populations. (C) 2011 Elsevier Inc. All rights reserved. C1 [Teng, Edmond; Frautschy, Sally A.; Cole, Gregory M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Kepe, Vladimir; Liu, Jie; Satyamurthy, Nagichettiar; Cole, Graham B.; Huang, Sung-Cheng; Barrio, Jorge R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Frautschy, Sally A.; Yang, Fusheng; Chen, Ping-Ping; Jones, Mychica R.; Cole, Gregory M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Small, Gary W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Teng, Edmond; Frautschy, Sally A.; Yang, Fusheng; Chen, Ping-Ping; Jones, Mychica R.; Cole, Gregory M.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Teng, E (reprint author), W Los Angeles VA Healthcare Ctr, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eteng@ucla.edu; vkepe@mednet.ucla.edu FU National Institute on Aging [P50 AG 16570, RC1 AG 035878, K08 AG 34628]; National Institutes of Health [P01 AG025831]; VA Merit Review Award Program; John Douglas French Alzheimer's Foundation; Brotman Foundation FX This research was supported by grants from the National Institute on Aging (P50 AG 16570 [pilot grants to ET, VK], RC1 AG 035878 [to GMC, SAF], K08 AG 34628 [to ET; jointly sponsored by NIA, AFAR, the John A. Hartford Foundation, the Atlantic Philanthropies, the Starr Foundation and an anonymous donor]), National Institutes of Health (P01 AG025831), VA Merit Review Award Program (to GMC, SAF), the John Douglas French Alzheimer's Foundation, and the Brotman Foundation. The funding sources had no involvement in study design; collection, analysis and interpretation of data; writing of the report; or the decision to submit the report for publication. We would like to thank Gerald Timbol for his management of the animal breeding colony and Waldemar Ladno and Judy Edwards for their assistance NR 55 TC 22 Z9 23 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD SEP PY 2011 VL 43 IS 3 BP 565 EP 575 DI 10.1016/j.nbd.2011.05.003 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 796GX UT WOS:000293040900005 PM 21605674 ER PT J AU Hubbard, CS Labus, JS Bueller, J Stains, J Suyenobu, B Dukes, GE Kelleher, DL Tillisch, K Naliboff, BD Mayer, EA AF Hubbard, Catherine S. Labus, Jennifer S. Bueller, Joshua Stains, Jean Suyenobu, Brandall Dukes, George E. Kelleher, Dennis L. Tillisch, Kirsten Naliboff, Bruce D. Mayer, Emeran A. TI Corticotropin-Releasing Factor Receptor 1 Antagonist Alters Regional Activation and Effective Connectivity in an Emotional-Arousal Circuit during Expectation of Abdominal Pain SO JOURNAL OF NEUROSCIENCE LA English DT Article ID IRRITABLE-BOWEL-SYNDROME; LOCUS-COERULEUS NEURONS; IBS PATIENTS; NORADRENERGIC NEURONS; BEHAVIORAL-RESPONSES; ANTICIPATORY ANXIETY; SEX-DIFFERENCES; MOTOR FUNCTION; PRIMATE BRAIN; STRESS AB Alterations in corticotropin-releasing factor (CRF) signaling pathways have been implicated in irritable bowel syndrome (IBS) pathophysiology. We aimed to (1) determine the effect of the selective CRF receptor 1 antagonist (CRF(1)) GW876008 relative to placebo, on regional activation and effective connectivity of a stress-related emotional-arousal circuit during expectation of abdominal pain using functional magnetic resonance imaging in human subjects with a diagnosis of IBS and healthy controls (HCs), and (2) examine GW876008 effects on state-trait anxiety and hypothalamic-pituitary-adrenal (HPA) axis response. Although there were no drug-related effects on peripheral HPA activity, significant central effects were observed in brain regions associated with the stress response. Effective connectivity analysis showed drug-induced normalizations between key regions of the emotional-arousal circuit in patients. During pain expectation, orally administered GW876008 relative to placebo produced significant blood oxygen level-dependent (BOLD) signal reductions in the amygdala, hippocampus, insula, anterior cingulate, and orbitomedial prefrontal cortices across groups. Patients showed significantly greater BOLD responses in the left locus coeruleus and hypothalamus after placebo compared with HCs, and BOLD signal decreases in the left hypothalamus after drug. The inhibitory effects of GW876008 in the hypothalamus in patients were moderated by anxiety; patients having average and high levels of state anxiety showed drug-related BOLD decreases. GW876008 represents a novel tool for elucidating the neuronal mechanisms and circuitry underlying hyperactivation of CRF/CRF(1) signaling and its role in IBS pathophysiology. The unique state anxiety effects observed suggest a potential pathway for therapeutic benefit of CRF(1) receptor antagonism for patients with stress-sensitive disorders. C1 [Mayer, Emeran A.] Univ Calif Los Angeles, Ctr Neurobiol Stress, Div Digest Dis, Los Angeles, CA 90095 USA. [Hubbard, Catherine S.; Bueller, Joshua; Stains, Jean; Suyenobu, Brandall; Tillisch, Kirsten; Mayer, Emeran A.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. [Mayer, Emeran A.] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90095 USA. [Labus, Jennifer S.; Naliboff, Bruce D.; Mayer, Emeran A.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. [Naliboff, Bruce D.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Dukes, George E.; Kelleher, Dennis L.] GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA. RP Mayer, EA (reprint author), Univ Calif Los Angeles, Ctr Neurobiol Stress, Div Digest Dis, CHS 47-122,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM emayer@ucla.edu OI Hubbard, Catherine/0000-0002-9139-2198 FU GlaxoSmithKline; NIH [R01 DK 48351, P50 DK 64539, R24 AT002681, K23 DK 073451-05, K08 DK 071626, T32-DK07180-34] FX This research was supported by GlaxoSmithKline, NIH Grants R01 DK 48351, P50 DK 64539, R24 AT002681, K23 DK 073451-05, and K08 DK 071626, and NIH GI Training Grant T32-DK07180-34. We thank Dr. Yvette Tache for valuable comments to this manuscript. NR 69 TC 44 Z9 46 U1 3 U2 10 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 31 PY 2011 VL 31 IS 35 BP 12491 EP 12500 DI 10.1523/JNEUROSCI.1860-11.2011 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 814KV UT WOS:000294451900013 PM 21880911 ER PT J AU Stetler, CB Damschroder, LJ Helfrich, CD Hagedorn, HJ AF Stetler, Cheryl B. Damschroder, Laura J. Helfrich, Christian D. Hagedorn, Hildi J. TI A Guide for applying a revised version of the PARIHS framework for implementation SO IMPLEMENTATION SCIENCE LA English DT Article ID QUERI SERIES; CONCEPTUAL-FRAMEWORK; PROMOTING ACTION; MODEL; CONTEXT; FACILITATION; EXPLORATION; INSTRUMENT; CARE AB Background: Based on a critical synthesis of literature on use of the Promoting Action on Research Implementation in Health Services (PARIHS) framework, revisions and a companion Guide were developed by a group of researchers independent of the original PARIHS team. The purpose of the Guide is to enhance and optimize efforts of researchers using PARIHS in implementation trials and evaluations. Methods: Authors used a planned, structured process to organize and synthesize critiques, discussions, and potential recommendations for refinements of the PARIHS framework arising from a systematic review. Using a templated form, each author independently recorded key components for each reviewed paper; that is, study definitions, perceived strengths/limitations of PARIHS, other observations regarding key issues and recommendations regarding needed refinements. After reaching consensus on these key components, the authors summarized the information and developed the Guide. Results: A number of revisions, perceived as consistent with the PARIHS framework's general nature and intent, are proposed. The related Guide is composed of a set of reference tools, provided in Additional files. Its core content is built upon the basic elements of PARIHS and current implementation science. Conclusions: We invite researchers using PARIHS for targeted evidence-based practice (EBP) implementations with a strong task-orientation to use this Guide as a companion and to apply the revised framework prospectively and comprehensively. Researchers also are encouraged to evaluate its use relative to perceived strengths and issues. Such evaluations and critical reflections regarding PARIHS and our Guide could thereby promote the framework's continued evolution. C1 [Stetler, Cheryl B.] Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA 02215 USA. [Damschroder, Laura J.] VA Ann Arbor Healthcare Syst, HSR&D Ctr Clin Management Res & Diabet QUERI, Ann Arbor, MI USA. [Helfrich, Christian D.] VA Puget Sound Healthcare Syst, NW HSR&D Ctr Excellence, Seattle, WA USA. [Helfrich, Christian D.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Hagedorn, Hildi J.] Minneapolis VA Med Ctr, VA Substance Use Disorders Qual Enhancement Res, Minneapolis, MN USA. [Hagedorn, Hildi J.] Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55455 USA. RP Stetler, CB (reprint author), Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA 02215 USA. EM cheryl.stetler@comcast.net RI Helfrich, Christian/D-2382-2016 OI Helfrich, Christian/0000-0002-9827-4768; Damschroder, Laura/0000-0002-3657-8459 FU U.S. Department of Veterans Affairs, Office of Research and Development Health Services FX This material is based upon work supported by the U.S. Department of Veterans Affairs, Office of Research and Development Health Services R&D Program. NR 37 TC 89 Z9 90 U1 2 U2 27 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 30 PY 2011 VL 6 AR 99 DI 10.1186/1748-5908-6-99 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 828AJ UT WOS:000295472200001 PM 21878092 ER PT J AU Egan, BM Zhao, YM Axon, RN Brzezinski, WA Ferdinand, KC AF Egan, Brent M. Zhao, Yumin Axon, R. Neal Brzezinski, Walter A. Ferdinand, Keith C. TI Uncontrolled and Apparent Treatment Resistant Hypertension in the United States, 1988 to 2008 SO CIRCULATION LA English DT Article DE epidemiology; hypertension; population; race/ethnicity ID HIGH-BLOOD-PRESSURE; NUTRITION EXAMINATION SURVEY; JOINT NATIONAL COMMITTEE; DIABETES-MELLITUS; US POPULATION; ADULTS; HEALTH; PREVALENCE; TRENDS; AWARENESS AB Background-Despite progress, many hypertensive patients remain uncontrolled. Defining characteristics of uncontrolled hypertensives may facilitate efforts to improve blood pressure control. Methods and Results-Subjects included 13 375 hypertensive adults from National Health and Nutrition Examination Surveys (NHANESs) subdivided into 1988 to 1994, 1999 to 2004, and 2005 to 2008. Uncontrolled hypertension was defined as blood pressure >= 140/>= 90 mm Hg and apparent treatment-resistant hypertension (aTRH) when subjects reported taking >= 3 antihypertensive medications. Framingham 10-year coronary risk was calculated. Multivariable logistic regression was used to identify clinical characteristics associated with untreated, treated uncontrolled on 1 to 2 blood pressure medications, and aTRH across all 3 survey periods. More than half of uncontrolled hypertensives were untreated across surveys, including 52.2% in 2005 to 2008. Clinical factors linked with untreated hypertension included male sex, infrequent healthcare visits (0 to 1 per year), body mass index < 25 kg/m(2), absence of chronic kidney disease, and Framingham 10-year coronary risk < 10% (P < 0.01). Most treated uncontrolled patients reported taking 1 to 2 blood pressure medications, a proxy for therapeutic inertia. This group was older, had higher Framingham 10-year coronary risk than patients controlled on 1 to 2 medications (P < 0.01), and comprised 34.4% of all uncontrolled and 72.0% of treated uncontrolled patients in 2005 to 2008. We found that aTRH increased from 15.9% (1998-2004) to 28.0% (2005-2008) of treated patients (P < 0.001). Clinical characteristics associated with aTRH included >= 4 visits per year, obesity, chronic kidney disease, and Framingham 10-year coronary risk > 20% (P < 0.01). Conclusion-Untreated, undertreated, and aTRH patients have consistent characteristics that could inform strategies to improve blood pressure control by decreasing untreated hypertension, reducing therapeutic inertia in undertreated patients, and enhancing therapeutic efficiency in aTRH. (Circulation. 2011; 124: 1046-1058.) C1 [Egan, Brent M.; Zhao, Yumin; Axon, R. Neal; Brzezinski, Walter A.] Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Axon, R. Neal] Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charlestown, MA USA. [Ferdinand, Keith C.] Emory Univ, Div Cardiol, Dept Med, Atlanta, GA 30322 USA. RP Egan, BM (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, 135 Rutledge Ave,1230 RT, Charleston, SC 29425 USA. EM eganbm@musc.edu FU state of South Carolina (Hypertension Initiative), National Institutes of Health (NIH), National Heart, Lung and Blood Institute [HL07080684]; NIH, National Institute of Diabetes and Digestive and Kidney Diseases [DK067615]; NIH, National Institute of Neurological Disorders and Stroke [NS058728]; US Army [W81XWH-10-2-0057]; Daiichi-Sankyo; Novartis; Takeda FX This work was supported in part by the state of South Carolina (Hypertension Initiative), National Institutes of Health (NIH) R01 National Heart, Lung and Blood Institute HL07080684, NIH R01 National Institute of Diabetes and Digestive and Kidney Diseases DK067615, NIH R01 National Institute of Neurological Disorders and Stroke NS058728, and US Army W81XWH-10-2-0057. The funding agencies were not involved in the design or conduct of the study; collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript.; Dr Egan has received grant support from Daiichi-Sankyo, Novartis, and Takeda; has served as a lecturer with honoraria on CME-accredited programs for the American Society of Hypertension Carolinas-Georgia-Florida Chapter and International Society of Hypertension in Blacks; and has been a consultant to NicOx. Dr Ferdinand has served on the speakers' bureau at AstraZeneca, Novartis, Forest, and Daiichi-Sankyo; has received honoraria from AstraZeneca, Novartis, and Forest; and has served as a consultant/advisory board member for AstraZeneca, Novartis, and Forest. The other authors report no conflicts. NR 35 TC 249 Z9 258 U1 1 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 30 PY 2011 VL 124 IS 9 BP 1046 EP 1058 DI 10.1161/CIRCULATIONAHA.111.030189 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 813BF UT WOS:000294340400015 PM 21824920 ER PT J AU Dewland, TA Pellegrini, CN Wang, YF Marcus, GM Keung, E Varosy, PD AF Dewland, Thomas A. Pellegrini, Cara N. Wang, Yongfei Marcus, Gregory M. Keung, Edmund Varosy, Paul D. TI Dual-Chamber Implantable Cardioverter-Defibrillator Selection Is Associated With Increased Complication Rates and Mortality Among Patients Enrolled in the NCDR Implantable Cardioverter-Defibrillator Registry SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE complication; defibrillator; dual-chamber ICD ID DETECTION ENHANCEMENTS; INAPPROPRIATE THERAPY; TRIAL AB Objectives The aim of this study was to compare single-versus dual-chamber implantable cardioverter-defibrillator (ICD) implantation and complication rates in a large, real-world population. Background The majority of patients enrolled in ICD efficacy trials received single-chamber devices. Although dual-chamber ICDs offer theoretical advantages over single-chamber defibrillators, the clinical superiority of dual-chamber models has not been conclusively proven, and they may increase complications. Methods The National Cardiovascular Data Registry ICD Registry was used to examine the association between baseline characteristics and device selection in 104,049 patients receiving single-and dual-chamber ICDs between January 1, 2006, and December 31, 2007. A longitudinal cohort design was then used to determine in-hospital complication rates. Results Dual-chamber devices were implanted in 64,489 patients (62%). Adverse events were more frequent with dual-chamber than with single-chamber device implantation (3.17% vs. 2.11%, p < 0.001), as was the rate of inhospital mortality (0.40% vs. 0.23%, p < 0.001). After adjusting for demographics, medical comorbidities, diagnostic test data, and ICD indication, the odds of any complication (odds ratio: 1.40; 95% confidence interval: 1.28 to 1.52; p < 0.001) and in-hospital mortality (odds ratio: 1.45; 95% confidence interval: 1.20 to 1.74; p < 0.001) were increased with dual-chamber versus single-chamber ICD implantation. Conclusions In this large, multicenter cohort of patients, dual-chamber ICD use was common. Dual-chamber device implantation was associated with increases in periprocedural complications and in-hospital mortality compared with single-chamber defibrillator selection. (J Am Coll Cardiol 2011; 58: 1007-13) (C) 2011 by the American College of Cardiology Foundation C1 [Varosy, Paul D.] Univ Colorado, Denver Vet Affairs Med Ctr, VA Eastern Colorado Hlth Care Syst, Denver, CO 80220 USA. [Dewland, Thomas A.] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. [Pellegrini, Cara N.; Marcus, Gregory M.; Keung, Edmund] Univ Calif San Francisco, Electrophysiol Sect, San Francisco, CA 94143 USA. [Wang, Yongfei] Yale Univ, Dept Med, New Haven, CT 06520 USA. [Pellegrini, Cara N.; Keung, Edmund] VA Med Ctr San Francisco, Cardiol Sect, San Francisco, CA USA. [Varosy, Paul D.] Colorado Cardiovasc Outcomes Res Grp, Denver, CO USA. RP Varosy, PD (reprint author), Univ Colorado, Denver Vet Affairs Med Ctr, VA Eastern Colorado Hlth Care Syst, 1055 Clermont St, Denver, CO 80220 USA. EM paul.varosy@va.gov FU Veterans Administration Office of Health Services Research and Development [RCD 04-115-2]; St. Jude Medical; Biotronik FX Funding for this study was provided in part by a Research Career Development Award (RCD 04-115-2 to Dr. Varosy) from the Veterans Administration Office of Health Services Research and Development. Dr. Marcus has received research funding from St. Jude Medical and speaker's fees from Biotronik and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 15 TC 65 Z9 68 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 30 PY 2011 VL 58 IS 10 BP 1007 EP 1013 DI 10.1016/j.jacc.2011.04.039 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 811JR UT WOS:000294205900004 PM 21867834 ER PT J AU Cardenas, VA Samuelson, K Lenoci, M Studholme, C Neylan, TC Marmar, CR Schuff, N Weiner, MW AF Cardenas, Valerie A. Samuelson, Kristin Lenoci, Maryann Studholme, Colin Neylan, Thomas C. Marmar, Charles R. Schuff, Norbert Weiner, Michael W. TI Changes in brain anatomy during the course of posttraumatic stress disorder SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Deformation morphometry; Longitudinal; MRI; Neuropsychological testing; PTSD; Vietnam veterans ID ADMINISTERED PTSD SCALE; HIPPOCAMPAL VOLUME; N-ACETYLASPARTATE; MEMORY; SURVIVORS; TRAUMA; ABUSE; MRI; CINGULATE; ANTERIOR AB The goal of this study was to determine whether posttraumatic stress disorder (PTSD) was associated with an increase in time-related decline in macrostructural brain volume and whether these changes were associated with accelerated cognitive decline. To quantify brain structure, three-dimensional T1 weighted MRI scans were performed at baseline and again after a minimum of 24 months in 25 patients with PTSD (PTSD+) and 22 controls (PTSD-). Longitudinal changes in brain volume were measured using deformation morphometry. For the group as a whole. PTSD+ patients did not show significant ongoing brain atrophy compared to PTSD-. PTSD+ patients were then subgrouped into those with decreasing or increasing symptoms. We found little evidence for brain markers of accelerated atrophy in PTSD+ veterans whose symptoms improved over time, with only a small left parietal region showing greater ongoing tissue loss than PTSD-. PTSD patients whose symptoms increased over time showed accelerated atrophy throughout the brain, particularly brainstem and frontal and temporal lobes. Lastly, for the sample as a whole, greater rates of brain atrophy were associated with greater rates of decline in verbal memory and delayed facial recognition. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Cardenas, Valerie A.] Univ Calif San Francisco, Dept Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Cardenas, Valerie A.; Samuelson, Kristin; Lenoci, Maryann; Neylan, Thomas C.; Marmar, Charles R.; Schuff, Norbert; Weiner, Michael W.] San Francisco VA Med Ctr, San Francisco, CA USA. [Samuelson, Kristin] Alliant Int Univ, San Francisco, CA USA. [Marmar, Charles R.] NYU, New York, NY USA. RP Cardenas, VA (reprint author), Univ Calif San Francisco, Dept Vet Affairs Med Ctr, 4150 Clement St,114M, San Francisco, CA 94121 USA. EM valerie.cardenas-nicolson@ucsf.edu RI Schueter, nicos/A-3625-2014 FU DOD Center of Excellence [W81XWH-05-2-0094 I (PI: Cardenas)]; NIBIB [R03EB8136]; Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC); Department of Veterans Affairs; NCRR [P41RR023953] FX We are grateful to the staff at the Center for Imaging of Neurodegenerative Diseases at the San Francisco VA Hospital for the MRI scanning, and to Linda Chao, Susanne Mueller, Brigitte Apfel, and Tim Durazzo for their helpful comments. This work was partially supported by a DOD Center of Excellence Grant W81XWH-05-2-0094 I (PI: Cardenas), NIBIB R03EB8136 (PI: Cardenas), the Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), a Department of Veterans Affairs Merit Award Grant (PI: Weiner), and NCRR P41RR023953. NR 47 TC 16 Z9 18 U1 2 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD AUG 30 PY 2011 VL 193 IS 2 BP 93 EP 100 DI 10.1016/j.pscychresns.2011.01.013 PG 8 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 799CA UT WOS:000293259900005 PM 21683556 ER PT J AU Rynkiewicz, D Rathkopf, M Sim, I Waytes, AT Hopkins, RJ Giri, L DeMuria, D Ransom, J Quinn, J Nabors, GS Nielsen, CJ AF Rynkiewicz, Dianna Rathkopf, Melinda Sim, Iain Waytes, A. Thomas Hopkins, Robert J. Giri, Lallan DeMuria, Deborah Ransom, Janet Quinn, James Nabors, Gary S. Nielsen, Carl J. TI Marked enhancement of the immune response to BioThrax (R) (Anthrax Vaccine Adsorbed) by the TLR9 agonist CPG 7909 in healthy volunteers SO VACCINE LA English DT Article DE BioThrax; Anthrax Vaccine Adsorbed; CPG 7909; CpG; Oligodeoxynucleotide; Clinical trial; Adjuvant ID LETHAL TOXIN NEUTRALIZATION; INHALATIONAL ANTHRAX; BACILLUS-ANTHRACIS; POSTEXPOSURE PROPHYLAXIS; PROTECTIVE ANTIGEN; IMMUNOGLOBULIN-G; ADVERSE EVENTS; UNITED-STATES; OLIGONUCLEOTIDES; ADJUVANT AB Immunization with BioThrax (R) (Anthrax Vaccine Adsorbed) is a safe and effective means of preventing anthrax. Animal studies have demonstrated that the addition of CpG DNA adjuvants to BioThrax can markedly increase the immunogenicity of the vaccine, increasing both serum anti-protective antigen (PA) antibody and anthrax toxin-neutralizing antibody (TNA) concentrations. The immune response to CpG-adjuvanted BioThrax in animals was not only stronger, but was also more rapid and led to higher levels of protection in spore challenge models. The B-class CpG DNA adjuvant CPG 7909, a 24-base synthetic, single-strand oligodeoxynucleotide, was evaluated for its safety profile and adjuvant properties in a Phase 1 clinical trial. A double-blind study was performed in which 69 healthy subjects, age 18-45 years, were randomized to receive three doses of either: (1) BioThrax alone, (2)1 mg of CPG 7909 alone or (3) BioThrax plus 1 mg of CPG 7909, all given intramuscularly on study days 0, 14 and 28. Subjects were monitored for IgG to PA by ELISA and for TNA titers through study day 56 and for safety through month 6. CPG 7909 increased the antibody response by 6-8-fold at peak, and accelerated the response by 3 weeks compared to the response seen in subjects vaccinated with BioThrax alone. No serious adverse events related to study agents were reported, and the combination was considered to be reasonably well tolerated. The marked acceleration and enhancement of the immune response seen by combining BioThrax and CPG 7909 offers the potential to shorten the course of immunization and reduce the time to protection, and may be particularly useful in the setting of post-exposure prophylaxis. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Waytes, A. Thomas; Hopkins, Robert J.; Giri, Lallan; Nabors, Gary S.] Emergent BioSolut Inc, Gaithersburg, MD 20879 USA. [Waytes, A. Thomas; Hopkins, Robert J.; Giri, Lallan; Nabors, Gary S.] Emergent BioSolut Inc, Lansing, MI USA. [Rynkiewicz, Dianna] Univ Texas San Antonio, Hlth Sci Ctr, San Antonio, TX USA. [Rynkiewicz, Dianna] Vet Adm Hosp, San Antonio, TX USA. [Rathkopf, Melinda; Quinn, James] USAF, Med Ctr, San Antonio, TX USA. [Sim, Iain; DeMuria, Deborah] Coley Pharmaceut Grp Inc, Wellesley, MA USA. [Ransom, Janet] Fast Track Drugs & Biol, Potomac, MD USA. [Nielsen, Carl J.] DARPA DSO, Arlington, VA USA. RP Nabors, GS (reprint author), Emergent BioSolut Inc, Gaithersburg, MD 20879 USA. EM iain.s.sim@gmail.com; ddemuria@gmail.com; naborsg@ebsi.com FU Defense Advanced Research Projects Administration (DARPA) [DAAD1903C0002]; U.S. Army Research Office FX The authors would like to acknowledge the support of the Defense Advanced Research Projects Administration (DARPA; contract DAAD1903C0002) and the U.S. Army Research Office. The authors also acknowledge the assistance of Drs. John Carney and Joseph Bielitzki who served as Program Managers during this study and Dr. Brett Giroir, Deputy Director, DARPA/DSO. In addition, the authors would like to thank the clinical staff and the volunteers of the U.S.A.F. Medical Center Wilford Hall and the University of Texas Medical Center and Veterans' Administration Center; Drs. Arthur Krieg, John Whisnant, and Mohamed El Adhami (Coley); Drs. Paul Hine and David Willis, and Cheryl Enger (Emergent BioSolutions); Capt. (Dr.) Robb Rowley (U.S.A.F.); Wendy Johnson for serological testing (USAMRIID); and Dr. Rob Carnes (BioSciences Intl., now Battelle). The authors dedicate this work to the late Drs. Carl Nielsen and Dianna Rynkiewicz. NR 42 TC 36 Z9 39 U1 1 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 26 PY 2011 VL 29 IS 37 BP 6313 EP 6320 DI 10.1016/j.vaccine.2011.05.047 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 825AR UT WOS:000295243800021 PM 21624418 ER PT J AU Albert, RK Connett, J Bailey, WC Casaburi, R Cooper, JAD Criner, GJ Curtis, JL Dransfield, MT Han, MLK Lazarus, SC Make, B Marchetti, N Martinez, FJ Madinger, NE McEvoy, C Niewoehner, DE Porsasz, J Price, CS Reilly, J Scanlon, PD Sciurba, FC Scharf, SM Washko, GR Woodruff, PG Anthonisen, NR AF Albert, Richard K. Connett, John Bailey, William C. Casaburi, Richard Cooper, J. Allen D., Jr. Criner, Gerard J. Curtis, Jeffrey L. Dransfield, Mark T. Han, MeiLan K. Lazarus, Stephen C. Make, Barry Marchetti, Nathaniel Martinez, Fernando J. Madinger, Nancy E. McEvoy, Charlene Niewoehner, Dennis E. Porsasz, Janos Price, Connie S. Reilly, John Scanlon, Paul D. Sciurba, Frank C. Scharf, Steven M. Washko, George R. Woodruff, Prescott G. Anthonisen, Nicholas R. CA COPD Clinical Res Network TI Azithromycin for Prevention of Exacerbations of COPD SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; FLUTICASONE PROPIONATE; CYSTIC-FIBROSIS; HEALTH OUTCOMES; TIOTROPIUM; SALMETEROL; ERYTHROMYCIN; MANAGEMENT; FREQUENCY AB Background Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases. Methods We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval. Results A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P < 0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P = 0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P< 0.001). The scores on the St. George's Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [+/- SD] decrease of 2.8 +/- 12.8 vs. 0.6 +/- 11.4, P = 0.004); the percentage of participants with more than the minimal clinically important difference of -4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P = 0.03). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P = 0.04). Conclusions Among selected subjects with COPD, azithromycin taken daily for 1 year, when added to usual treatment, decreased the frequency of exacerbations and improved quality of life but caused hearing decrements in a small percentage of subjects. Although this intervention could change microbial resistance patterns, the effect of this change is not known. (Funded by the National Institutes of Health; ClinicalTrials. gov number, NCT00325897.) C1 Denver Hlth, Med Serv, Denver, CO USA. [Albert, Richard K.; Price, Connie S.] Univ Colorado Denver, Hlth Sci Ctr, Dept Med, Denver, CO USA. Natl Jewish Hlth, Div Pulm Med, Denver, CO USA. [Madinger, Nancy E.; Price, Connie S.] Univ Colorado Denver, Dept Med, Div Infect Dis, Denver, CO USA. [Connett, John] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [Niewoehner, Dennis E.; Reilly, John] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Niewoehner, Dennis E.; Reilly, John] Minneapolis Vet Affairs VA Med Ctr, Med Serv, Div Pulm Med, Minneapolis, MN USA. [Bailey, William C.; Cooper, J. Allen D., Jr.; Dransfield, Mark T.] Univ Alabama, Dept Med, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. [Dransfield, Mark T.] Birmingham VA Med Ctr, Pulm Sect, Birmingham, AL USA. [Casaburi, Richard; Porsasz, Janos] Harbor UCLA Med Ctr, Dept Med, Div Resp & Crit Care Physiol & Med, Torrance, CA 90509 USA. [Criner, Gerard J.; Marchetti, Nathaniel] Temple Univ, Div Pulm & Crit Care Med, Dept Med, Philadelphia, PA 19122 USA. [Curtis, Jeffrey L.; Han, MeiLan K.; Martinez, Fernando J.] Univ Michigan, Dept Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA. [Curtis, Jeffrey L.] Ann Arbor VA Med Ctr, Div Pulm & Crit Care Med, Ann Arbor, MI USA. [Lazarus, Stephen C.; Woodruff, Prescott G.] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA USA. [Lazarus, Stephen C.; Woodruff, Prescott G.] Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA USA. [McEvoy, Charlene] HealthPartners Res Fdn, Pulm Crit Care & Sleep Dept, St Paul, MN USA. [Scanlon, Paul D.] Mayo Clin, Div Pulm & Crit Care Med, Rochester, MN USA. [Sciurba, Frank C.] Univ Pittsburgh, Dept Med, Div Pulm & Crit Care Med, Pittsburgh, PA USA. [Scharf, Steven M.] Univ Maryland, Dept Med, Div Pulm & Crit Care, Baltimore, MD 21201 USA. [Washko, George R.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Anthonisen, Nicholas R.] Resp Hosp, Winnipeg, MB, Canada. RP Albert, RK (reprint author), Dr Albert Denver Hlth, 777 Bannock St,MC 4000, Denver, CO 80204 USA. EM ralbert@dhha.org RI Gough, Ethan/B-8633-2012; Wendt, Chris/C-6823-2012 OI Curtis, Jeffrey/0000-0001-5191-4847 FU National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health [U10 HL074407, U10 HL074408, U10 HL074409, U10 HL074416, U10 HL074418, U10 HL074422, U10 HL074424, U10 HL074428, U10 HL074431, U10 HL074439, U10 HL074441]; Division of Lung Diseases of the NHLBI; National Center for Research Resources [M01]; Gilead Sciences; Elsevier; Novartis Pharmaceuticals; Forest Pharmaceuticals; Theratechnologies; Breathe Technologies; Medtronic Spinal and Biologics; Boehringer Ingelheim; Philips Respironics; Novartis; Actelion Pharmaceuticals; AstraZeneca; Pfizer; Roche; Osiris Therapeutics; GlaxoSmithKline; Watkins; Louri; Roll and Change; Lawrence R. Dry Associates; Starnes Davis Florie LLP; Walker; Tipps Malone PLC; Moore; Ingram Johnson Steele; Farris; Riley Pitt, LLP; Phillips Pharmaceuticals; Uptake Medical; Dey; Boston Scientific; CSL Behring; Astellas Pharma; Talecris Biotherapeutics; Chiesi Pharmaceuticals; MedImmune-Astra Zeneca; Merck; Pearl Therapeutics; UBC; Mpex Pharmaceuticals and Ikaria; Forest-Almirall; Nycomed-Forest; Bayer; Schering-Plough (Merck); HLS; Comgeniz; fb Communications; BoomComm; Elan; Genzyme; Quark Pharmaceuticals; Sanofi-Aventis; Associates in Medical Marketing and Castle Connolly; National Association for Continuing Education; Med-Ed; Potomac Pharma; Vox Medica; WebMD; Epocrates; Altana-Nycomed; Global; Johnson & Johnson-Centocor Ortho Biotech; MicroPhage; Cubist Pharmaceuticals; Quintiles; Sanofi Pasteur; BioCryst Pharmaceuticals; Accelr8 Technology; Robert Michael; Baxter Healthcare; Altana; Lippincott Williams Wilkins; Wolters Kluwer; Genentech FX Supported by grants (U10 HL074407, U10 HL074408, U10 HL074409, U10 HL074416, U10 HL074418, U10 HL074422, U10 HL074424, U10 HL074428, U10 HL074431, U10 HL074439, and U10 HL074441) from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. The COPD Clinical Research Network is supported by a Cooperative Agreement from the Division of Lung Diseases of the NHLBI. At some sites, General Clinical Research Center facilities were used; their M01 grants from the National Center for Research Resources are listed in the Supplementary Appendix.; Dr. Albert reports receiving consulting fees from Gilead Sciences, fees for expert testimony from the Bruce Fagel Law Firm, and royalties from Elsevier, and being named on a patent pending for a device that provides continuous monitoring of the elevation of the head of the bed (Denver Health and the University of Colorado); Dr. Casaburi, receiving payment for service on the advisory boards of Novartis Pharmaceuticals and Forest Pharmaceuticals, consulting fees from Theratechnologies, Breathe Technologies, Medtronic Spinal and Biologics, Boehringer Ingelheim, Philips Respironics, Novartis, and Actelion Pharmaceuticals, lecture fees from Boehringer Ingelheim, AstraZeneca, and Pfizer, holding stock in Inogen, and receiving grant support from Novartis, Roche, Boehringer Ingelheim, Osiris Therapeutics, Forest Pharmaceuticals, and GlaxoSmithKline, Breathe Technologies (pending), and Theratechnologies (pending); Dr. Cooper, receiving fees for expert testimony from Watkins, Louri, Roll and Change; Lawrence R. Dry & Associates; Starnes Davis Florie LLP; Walker, Tipps & Malone PLC; Moore, Ingram Johnson & Steele; and Farris, Riley & Pitt, LLP; and grant support from GlaxoSmithKline and Novartis; Dr. Criner, receiving consulting fees from Phillips Pharmaceuticals, GlaxoSmithKline, Uptake Medical, and Dey, grant support from Philips Respironics, GlaxoSmithKline, Boehringer Ingelheim, Novartis, and AstraZeneca, and royalties from Springer; Dr. Curtis, receiving grant support from Boehringer Ingelheim; Dr. Dransfield, receiving consulting fees from GlaxoSmithKline, Boehringer Ingelheim, and Forest Pharmaceuticals, grant support from GlaxoSmithKline, Boehringer Ingelheim, and Boston Scientific, and lecture fees from GlaxoSmithKline and Boehringer Ingelheim; Dr. Han, receiving payment for service on the advisory boards of CSL Behring, GlaxoSmithKline, and Boehringer Ingelheim, consulting fees from Genentech and Novartis, lecture fees from GlaxoSmithKline, CSL Behring, Boehringer Ingelheim, and Pfizer, royalties from UpToDate, and meeting expenses from AstraZeneca; Dr. Madinger, receiving honoraria in conjunction with the Merck Study Monitoring Antimicrobial Resistance Trends (SMART), the JMI Laboratories Sentry study, and the Eurofins Medinet Trust study; Dr. Make, receiving payment for service on the advisory boards of Forest Pharmaceuticals, AstraZeneca, Novartis, Dey, Nycomed, Philips Respironics, Schering-Plough (now Merck), SeQual, Embryon, Boehringer Ingelheim, Pfizer, and GlaxoSmithKline, consulting fees from Astellas Pharma, Talecris Biotherapeutics, and Chiesi Pharmaceuticals, lecture fees from GlaxoSmithKline, Boehringer Ingelheim, Pfizer, and Forest Pharmaceuticals, payment for manuscript preparation from AstraZeneca, payment for video presentation preparation from Boehringer Ingelheim and Pfizer, payment for document reviews from Spiration, and grant support from AstraZeneca, GlaxoSmithKline, Pfizer, Nabi Biopharmaceuticals, Boehringer Ingelheim, and Sunovion; Dr.; Martinez, receiving payment for service on the advisory boards of GlaxoSmithKline, MedImmune-Astra Zeneca, Merck, Pearl Therapeutics, Novartis, UBC, Mpex Pharmaceuticals and Ikaria, consulting fees from Forest-Almirall, Boehringer Ingelheim, Nycomed-Forest, Roche, Bayer, Schering-Plough (Merck), HLS, Talecris Biotherapeutics, Comgeniz, fb Communications, BoomComm, Actelion Pharmaceuticals, Elan, Genzyme, Quark Pharmaceuticals, Merck, Pfizer, and Sanofi-Aventis, royalties from Associates in Medical Marketing and Castle Connolly, lecture fees from GlaxoSmithKline, National Associaion for Continuing Education, Med-Ed, Potomac Pharma, Pfizer, Boehringer Ingelheim, Schering-Plough (Merck), Vox Medica, WebMD, Epocrates, AstraZeneca, and Altana-Nycomed, payment for development of educational presentations for HIT Global and UpToDate, and grant support from Boehringer Ingelheim, Gilead, Johnson & Johnson-Centocor Ortho Biotech, and Actelion Pharmaceuticals; Dr. McEvoy, receiving grant support from Boston Scientific and GlaxoSmithKline and lecture fees from Boehringer Ingelheim and GlaxoSmithKline; Dr. Niewoehner, receiving consulting fees from Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, Forest Research, Merck, Sanofi-Aventis, Bayer Schering Pharma, Nycomed, ProtAffin, and Pfizer; Dr. Porszasz, receiving consulting fees from Breathe Technologies, Boehringer Ingelheim, Novartis, and Forest Pharmaceuticals, and grant support from Boehringer Ingelheim, Forest Pharmaceuticals, Breathe Technologies (pending), and Novartis; Dr. Price, receiving consulting fees from Astellas Pharma, Cubist Pharmaceuticals, and Merck, providing expert testimony on transmission of hospital-associated infections, management of musculoskeletal infections, aminoglycoside toxicity, and diagnosis of infection, receiving grant support from MicroPhage, Cubist Pharmaceuticals, Quintiles, Sanofi Pasteur, BioCryst Pharmaceuticals, and Accelr8 Technology, and lecture fees from Robert Michael (a CME vendor), Cubist Pharmaceuticals, and Baxter Healthcare; Dr. Scanlon, receiving grant support from Altana, Boehringer Ingelheim, Dey, Forest Pharmaceuticals, GlaxoSmithKline, Novartis, and Pfizer and royalties from Lippincott Williams & Wilkins and Wolters Kluwer; Dr. Sciurba, receiving consulting fees from Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline and grant support from Pfizer and GlaxoSmithKline; Dr. Washko, receiving consulting fees from MedImmune and Spiration and being married to an employee of Merck Research Laboratories Division of Clinical Pharmacology; and Dr. Woodruff, receiving consulting fees from MedImmune, grant support from Genentech, and being a coinventor on a patent held jointly by his institution and Genentech. No other potential conflict of interest relevant to this article was reported. NR 42 TC 392 Z9 405 U1 5 U2 48 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 25 PY 2011 VL 365 IS 8 BP 689 EP 698 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 811JM UT WOS:000294205300004 PM 21864166 ER PT J AU Cermelli, S Ruggieri, A Marrero, JA Ioannou, GN Beretta, L AF Cermelli, Silvia Ruggieri, Anna Marrero, Jorge A. Ioannou, George N. Beretta, Laura TI Circulating MicroRNAs in Patients with Chronic Hepatitis C and Non-Alcoholic Fatty Liver Disease SO PLOS ONE LA English DT Article ID HEPATOCELLULAR-CARCINOMA; IN-VIVO; MIR-122; CANCER; VIRUS; EXPRESSION; TRANSLATION; BIOMARKERS; STEATOSIS; INFECTION AB MicroRNAs miR-122, miR-34a, miR-16 and miR-21 are commonly deregulated in liver fibrosis and hepatocellular carcinoma. This study examined whether circulating levels of these miRNAs correlate with hepatic histological disease severity in patients with chronic hepatitis C infection (CHC) or non-alcoholic fatty-liver disease (NAFLD) and can potentially serve as circulating markers for disease stage assessment. We first used an in vitro model of hepatitis C virus (HCV) infection to measure the extracellular levels of these four miRNAs. Whereas miR-21 extracellular levels were unchanged, extracellular levels of miR-122, miR-34a and to a lesser extent miR-16, steadily increased during the course of HCV infection, independently of viral replication and production. Similarly, in CHC patients, serum levels of miR-122, miR-34a and miR-16 were significantly higher than in control individuals, while miR-21 levels were unchanged. There was no correlation between the serum levels of any of these microRNAs and HCV viral loads. In contrast, miR-122 and miR-34a levels positively correlated with disease severity. Identical results were obtained in an independent cohort of CHC patients. We extended the study to patients with NAFLD. As observed in CHC patients, serum levels of miR-122, miR-34a and miR-16 were significantly higher in NAFLD patients than in controls, while miR-21 levels were unchanged. Again, miR-122 and miR-34a levels positively correlated with disease severity from simple steatosis to steatohepatitis. In both CHC and NAFLD patient groups, serum levels of miR-122 and miR-34a correlated with liver enzymes levels, fibrosis stage and inflammation activity. miR-122 levels also correlated with serum lipids in NAFLD patients. Conclusion: Serum levels of miR-34a and miR-122 may represent novel, noninvasive biomarkers of diagnosis and histological disease severity in patients with CHC or NAFLD. C1 [Cermelli, Silvia; Ruggieri, Anna; Beretta, Laura] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Ruggieri, Anna] Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, I-00161 Rome, Italy. [Marrero, Jorge A.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA USA. [Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. RP Cermelli, S (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. EM lberetta@fhcrc.org RI ruggieri, anna/C-9950-2015 FU National Institutes of Health [DK066840] FX This work was supported by grant DK066840 from the National Institutes of Health. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 205 Z9 212 U1 1 U2 18 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 AUG 23 PY 2011 VL 6 IS 8 AR e23937 DI 10.1371/journal.pone.0023937 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 811YA UT WOS:000294253500040 PM 21886843 ER PT J AU Massie, BM AF Massie, Barry M. TI Globalization of Clinical Trials How Should We Interpret Differences in Outcomes? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE beta-blocker; clinical trials; geography; heart failure; mortality ID CONGESTIVE-HEART-FAILURE; BUCINDOLOL; SURVIVAL C1 [Massie, Barry M.] San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA USA. [Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Massie, BM (reprint author), VA Med Ctr, Cardiol Div 111C, 4150 Clement St, San Francisco, CA 94121 USA. EM barry.massie@va.gov NR 13 TC 7 Z9 7 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 AUG 23 PY 2011 VL 58 IS 9 BP 923 EP 924 DI 10.1016/j.jacc.2011.04.027 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 808BC UT WOS:000293947100007 PM 21851880 ER PT J AU Teerlink, JR Clarke, CP Saikali, KG Lee, JH Chen, MM Escandon, RD Elliott, L Bee, R Habibzadeh, MR Goldman, JH Schiller, NB Malik, FI Wolff, AA AF Teerlink, John R. Clarke, Cyril P. Saikali, Khalil G. Lee, Jacqueline H. Chen, Michael M. Escandon, Rafael D. Elliott, Lyndsey Bee, Rachel Habibzadeh, Mohammad Reza Goldman, Jonathan H. Schiller, Nelson B. Malik, Fady I. Wolff, Andrew A. TI Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a first-in-man study SO LANCET LA English DT Article ID DECOMPENSATED HEART-FAILURE; TIME INTERVALS; ASSOCIATION; DIAGNOSIS; SURVIVE; UPDATE AB Background Decreased systolic function is central to the pathogenesis of heart failure in millions of patients worldwide, but mechanism-related adverse effects restrict existing inotropic treatments. This study tested the hypothesis that omecamtiv mecarbil, a selective cardiac myosin activator, will augment cardiac function in human beings. Methods In this dose-escalating, crossover study, 34 healthy men received a 6-h double-blind intravenous infusion of omecamtiv mecarbil or placebo once a week for 4 weeks. Each sequence consisted of three ascending omecamtiv mecarbil doses (ranging from 0.005 to 1.0 mg/kg per h) with a placebo infusion randomised into the sequence. Vital signs, blood samples, electrocardiographs (ECGs), and echocardiograms were obtained before, during, and after each infusion. The primary aim was to establish maximum tolerated dose (the highest infusion rate tolerated by at least eight participants) and plasma concentrations of omecamtiv mecarbil; secondary aims were evaluation of pharmacodynamic and pharmacokinetic characteristics, safety, and tolerability. This study is registered at ClinicalTrials.gov, number NCT01380223. Findings The maximum tolerated dose of omecamtiv mecarbil was 0.5 mg/kg per h. Omecamtiv mecarbil infusion resulted in dose-related and concentration-related increases in systolic ejection time (mean increase from baseline at maximum tolerated dose, 85 [SD 5] ms), the most sensitive indicator of drug effect (r(2)=0.99 by dose), associated with increases in stroke volume (15 [2] mL), fractional shortening (8% [1]), and ejection fraction (7% [1]; all p<0.0001). Omecamtiv mecarbil increased atrial contractile function, and there were no clinically relevant changes in diastolic function. There were no clinically significant dose-related adverse effects on vital signs, serum chemistries, ECGs, or adverse events up to a dose of 0.625 mg/kg per h. The dose-limiting toxic effect was myocardial ischaemia due to excessive prolongation of systolic ejection time. Interpretation These first-in-man data show highly dose-dependent augmentation of left ventricular systolic function in response to omecamtiv mecarbil and support potential clinical use of the drug in patients with heart failure. C1 [Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA 94121 USA. [Habibzadeh, Mohammad Reza; Schiller, Nelson B.] Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94121 USA. [Clarke, Cyril P.] ICON Dev Solut, UK Clin Res Unit, Manchester, Lancs, England. [Clarke, Cyril P.] Univ Manchester, Manchester, Lancs, England. [Saikali, Khalil G.; Lee, Jacqueline H.; Chen, Michael M.; Escandon, Rafael D.; Malik, Fady I.; Wolff, Andrew A.] Cytokinetics Inc, San Francisco, CA USA. [Elliott, Lyndsey; Bee, Rachel; Goldman, Jonathan H.] ICON Med Imaging, Warrington, PA USA. RP Teerlink, JR (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA 94121 USA. EM john.teerlink@ucsf.edu RI Teerlink, John/D-2986-2012 FU Amgen; Corthera; Cytokinetics; Merck; Novartis; Scios; Bayer; Nile Therapeutics; Cytokinetics (South San Francisco, CA, USA); Cytokinetics Inc. FX JRT has received research grants from Amgen, Corthera, Cytokinetics, Merck, Novartis, and Scios; and consulting fees from Bayer, Corthera, Cytokinetics, Merck, Nile Therapeutics, and Novartis. CPC is an employee of ICON Development Solutions (formerly Medeval). LE and RB are employees of ICON Medical Imaging. KGS, JHL, MMC, RDE, FIM, and AAW are employees of Cytokinetics, the sponsor of this study. MRH and NBS received research grants from ICON Medical Imaging. JHG is an employee of ICON Clinical Research, and formerly of ICON Medical Imaging, the echocardiogram core laboratory for this study.; This study was funded by Cytokinetics (South San Francisco, CA, USA).; Funding Cytokinetics Inc. NR 23 TC 74 Z9 77 U1 1 U2 7 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 AUG 20 PY 2011 VL 378 IS 9792 BP 667 EP 675 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 815EW UT WOS:000294509900026 PM 21856480 ER PT J AU Cleland, JGF Teerlink, JR Senior, R Nifontov, EM Mc Murray, JJV Lang, CC Tsyrlin, VA Greenberg, BH Mayet, J Francis, DP Shaburishvili, T Monaghan, M Saltzberg, M Neyses, L Wasserman, SM Lee, JH Saikali, KG Clarke, CP Goldman, JH Wolff, AA Malik, FI AF Cleland, John G. F. Teerlink, John R. Senior, Roxy Nifontov, Evgeny M. Mc Murray, John J. V. Lang, Chim C. Tsyrlin, Vitaly A. Greenberg, Barry H. Mayet, Jamil Francis, Darrel P. Shaburishvili, Tamaz Monaghan, Mark Saltzberg, Mitchell Neyses, Ludwig Wasserman, Scott M. Lee, Jacqueline H. Saikali, Khalil G. Clarke, Cyril P. Goldman, Jonathan H. Wolff, Andrew A. Malik, Fady I. TI The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial SO LANCET LA English DT Article ID RESYNCHRONIZATION THERAPY; CONSCIOUS DOGS; MILRINONE; MORTALITY AB Background Many patients with heart failure remain symptomatic and have a poor prognosis despite existing treatments. Decreases in myocardial contractility and shortening of ventricular systole are characteristic of systolic heart failure and might be improved by a new therapeutic class, cardiac myosin activators. We report the first study of the cardiac myosin activator, omecamtiv mecarbil, in patients with systolic heart failure. Methods We undertook a double-blind, placebo-controlled, crossover, dose-ranging, phase 2 trial investigating the effects of omecamtiv mecarbil (formerly CK-1827452), given intravenously for 2, 24, or 72 h to patients with stable heart failure and left ventricular systolic dysfunction receiving guideline-indicated treatment. Clinical assessment (including vital signs, echocardiograms, and electrocardiographs) and testing of plasma drug concentrations took place during and after completion of each infusion. The primary aim was to assess safety and tolerability of omecamtiv mecarbil. This study is registered at ClinicalTrials.gov, NCT00624442. Findings 45 patients received 151 infusions of active drug or placebo. Placebo-corrected, concentration-dependent increases in left ventricular ejection time (up to an 80 ms increase from baseline) and stroke volume (up to 9.7 mL) were recorded, associated with a small reduction in heart rate (up to 2.7 beats per min; p<0.0001 for all three measures). Higher plasma concentrations were also associated with reductions in end-systolic (decrease of 15 mL at >500 ng/mL, p=0.0026) and end-diastolic volumes (16 mL, p=0.0096) that might have been more pronounced with increased duration of infusion. Cardiac ischaemia emerged at high plasma concentrations (two patients, plasma concentrations roughly 1750 ng/mL and 1350 ng/mL). For patients tolerant of all study drug infusions, no consistent pattern of adverse events with either dose or duration emerged. Interpretation Omecamtiv mecarbil improved cardiac function in patients with heart failure caused by left ventricular dysfunction and could be the first in class of a new therapeutic agent. C1 [Cleland, John G. F.] Univ Hull, Dept Cardiol, Hull York Med Sch, Kingston Upon Hull HU6 7RX, N Humberside, England. [Teerlink, John R.] Univ Calif San Francisco, Cardiol Sect, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Senior, Roxy] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Senior, Roxy] Royal Brompton Hosp, London SW3 6LY, England. [Senior, Roxy] Northwick Pk Hosp & Clin Res Ctr, Harrow HA1 3UJ, Middx, England. [Nifontov, Evgeny M.] St Petersburg State Med Univ, St Petersburg, Russia. [Mc Murray, John J. V.] Univ Glasgow, Western Infirm, Glasgow G11 6NT, Lanark, Scotland. [Mc Murray, John J. V.] Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow G11 6NT, Lanark, Scotland. [Lang, Chim C.] Univ Dundee, Ctr Cardiovasc & Lung Biol, Div Med Sci, Dundee DD1 4HN, Scotland. [Tsyrlin, Vitaly A.] Almazov Fed Heart Blood & Endocrinol Ctr, St Petersburg, Russia. [Greenberg, Barry H.] Univ Calif San Diego Med Ctr, San Diego, CA USA. [Mayet, Jamil; Francis, Darrel P.] St Marys Hosp, London, England. [Shaburishvili, Tamaz] Diagnost Serv Clin, Tbilisi, Rep of Georgia. [Monaghan, Mark] Kings Coll Hosp London, London, England. [Saltzberg, Mitchell] Jefferson Med Coll, Christiana Care Hlth Syst, Newark, DE USA. [Neyses, Ludwig; Clarke, Cyril P.] Univ Manchester, Manchester, Lancs, England. [Neyses, Ludwig] Manchester Royal Infirm, Manchester Acad Hlth Sci Ctr, Manchester M13 9WL, Lancs, England. [Wasserman, Scott M.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Clarke, Cyril P.] ICON Dev Solut, UK Clin Res Unit, Manchester, Lancs, England. [Goldman, Jonathan H.] ICON Med Imaging, Warrington, PA USA. [Lee, Jacqueline H.; Saikali, Khalil G.; Wolff, Andrew A.; Malik, Fady I.] Cytokinetics Inc, San Francisco, CA USA. RP Cleland, JGF (reprint author), Univ Hull, Dept Cardiol, Hull York Med Sch, Castle Hill Hosp, Med Res Bldg, Kingston Upon Hull HU16 5JQ, East Yorkshire, England. EM j.g.cleland@hull.ac.uk RI Teerlink, John/D-2986-2012; mcmurray, john/B-2467-2013; Nifontov, Evgeniy/A-5954-2017 OI Cleland, John/0000-0002-1471-7016; mcmurray, john/0000-0002-6317-3975 FU Cytokinetics; Amgen; Cytokinetics Inc. FX JGFC, JRT, JJVM, and BHG have received research grants and consulting fees from Cytokinetics and Amgen, which is a licensee of omecamtiv mecarbil. RS, EMN, CCL, VAT, JM, DPF, TS, MM, MS, and LN have received research grants and consulting fees from Cytokinetics. SMW is an employee of Amgen. CPC is an employee of ICON Development Solutions (formerly Medeval, Manchester, UK). (HG is an employee of ICON Clinical Research, and formerly of ICON Medical Imaging, the echocardiogram core laboratory for this study. JHL, KGS, AAW, and FIM are employees of Cytokinetics, the sponsor of this study.; Funding: Cytokinetics Inc. NR 16 TC 114 Z9 120 U1 4 U2 15 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 AUG 20 PY 2011 VL 378 IS 9792 BP 676 EP 683 DI 10.1016/S0140-6736(11)61126-4 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 815EW UT WOS:000294509900027 PM 21856481 ER PT J AU Krum, H Teerlink, JR AF Krum, Henry Teerlink, John R. TI Heart Failure 2 Medical therapy for chronic heart failure SO LANCET LA English DT Article ID PLACEBO-CONTROLLED TRIAL; VENTRICULAR EJECTION FRACTION; RANDOMIZED CONTROLLED-TRIAL; CARDIAC-INSUFFICIENCY BISOPROLOL; ANGIOTENSIN-RECEPTOR BLOCKER; CONVERTING ENZYME-INHIBITOR; GISSI-HF TRIAL; DOUBLE-BLIND; CLINICAL-TRIALS; VASOPRESSIN ANTAGONIST AB Understanding of contemporary pharmacological therapy for chronic heart failure continues to evolve. In this Review, we discuss how findings from clinical trials have caused the roles of old therapies to be expanded and past treatment algorithms to be challenged. Several trials investigating preserved ejection fraction as a measure of heart failure had disappointing results, although important studies are in progress. Many novel therapeutic approaches for heart failure have emerged and are discussed in this review. The pharmacological treatments for heart failure continue to change, with many exciting possibilities for the future. C1 [Teerlink, John R.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA 94121 USA. [Krum, Henry] Monash Univ, Monash Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic 3004, Australia. [Teerlink, John R.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. RP Teerlink, JR (reprint author), San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA 94121 USA. EM john.teerlink@ucsf.edu RI Teerlink, John/D-2986-2012 FU Amgen; Vifor; Novartis; Servier; Bayer; Cytokinetics; Bristol-Myers Squibb; National Institutes of Health FX HK has received research grants from Amgen, Vifor, Novartis and Servier; and consulting fees from Novartis, Bayer and Amgen. JRT has received research grants from Amgen and Cytokinetics, Bristol-Myers Squibb, National Institutes of Health, and Novartis; and consulting fees from Amgen and Cytokinetics, and Novartis. NR 78 TC 36 Z9 43 U1 0 U2 7 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 AUG 20 PY 2011 VL 378 IS 9792 BP 713 EP 721 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 815EW UT WOS:000294509900031 PM 21856485 ER PT J AU Wood, AC Glasser, S Garvey, WT Kabagambe, EK Borecki, IB Tiwari, HK Tsai, MY Hopkins, PN Ordovas, JM Arnett, DK AF Wood, Alexis C. Glasser, Stephen Garvey, W. Timothy Kabagambe, Edmond K. Borecki, Ingrid B. Tiwari, Hemant K. Tsai, Michael Y. Hopkins, Paul N. Ordovas, Jose M. Arnett, Donna K. TI Lipoprotein Lipase S447X variant associated with VLDL, LDL and HDL diameter clustering in the MetS SO LIPIDS IN HEALTH AND DISEASE LA English DT Article DE GOLDN; lipoprotein; lipoprotein lipase; Metabolic syndrome ID GENE; DISEASE; RISK; LPL AB Background: Previous analysis clustered 1,238 individuals from the general population Genetics of Lipid Lowering Drugs Network (GOLDN) study by the size of their fasting very low-density, low-density and high-density lipoproteins (VLDL, LDL, HDL) using latent class analysis. From two of the eight identified groups (N = 251), similar to 75% of individuals met Adult Treatment Panel III criteria for the metabolic syndrome (MetS). Both showed small LDL diameter (mean = 19.9 nm); however, group 1 (N = 200) had medium VLDL diameter (mean = 53.1 nm) while group 2 had very large VLDL diameter (mean = 65.74 nm). Group 2 additionally showed significantly more insulin resistance (IR), and accompanying higher waist circumference and fasting glucose and triglycerides (all P < .01). Since lipoprotein lipase hydrolyzes triglyceride in the VLDL-LDL cascade, we examined whether these two patterns of lipoprotein diameter were associated with differences across two lipoprotein lipase (LPL) gene variants: D9N (rs1801177) and S447X (rs328). Findings: Mixed linear models that controlled for age, sex, center of data collection, and family pedigree revealed no differences between the two groups for the D9N polymorphism (P = .36). However, group 2 contained significantly more carriers (25%) of the 447X variant than group 1 (14%; P = .04). Conclusions: This was the first study this kind to show an association between LPL and large VLDL particle size within the MetS, a pattern associated with higher IR. Future work should extend this to larger samples to confirm these findings, and examine the long term outcomes of those with this lipoprotein diameter pattern. C1 [Wood, Alexis C.; Kabagambe, Edmond K.; Arnett, Donna K.] Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL USA. [Wood, Alexis C.; Tiwari, Hemant K.] Univ Alabama, Sch Publ Hlth, Sect Stat Genet, Dept Biostat, Birmingham, AL USA. [Glasser, Stephen] Univ Alabama, Div Prevent Med, Dept Med, Birmingham, AL USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Kabagambe, Edmond K.; Arnett, Donna K.] Univ Alabama, Sch Publ Hlth, Nutr Obes Res Ctr, Birmingham, AL USA. [Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA. [Tsai, Michael Y.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Hopkins, Paul N.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. [Ordovas, Jose M.] Tufts Univ, Jean Mayer US Dept Agr Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Ordovas, Jose M.] Ctr Nacl Invest Cardiovasc Madrid, Dept Epidemiol & Populat Genet, Madrid, Spain. RP Wood, AC (reprint author), Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL USA. EM LekkiWood@Gmail.com RI Frazier-Wood, Alexis (Lekki)/B-8053-2010 OI Frazier-Wood, Alexis (Lekki)/0000-0001-7616-2119; Ordovas, Jose/0000-0002-7581-5680 FU NHLBI [U01HL072524] FX This study was funded by NHLBI grant number U01HL072524. Financial disclosures: None to declare. Disclosure: All authors declare that they have no conflicts of interests. NR 11 TC 2 Z9 5 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-511X J9 LIPIDS HEALTH DIS JI Lipids Health Dis. PD AUG 19 PY 2011 VL 10 AR 143 DI 10.1186/1476-511X-10-143 PG 4 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 828RN UT WOS:000295520300001 PM 21854610 ER PT J AU Chuang, PY Dai, Y Liu, RJ He, HL Kretzler, M Jim, B Cohen, CD He, JC AF Chuang, Peter Y. Dai, Yan Liu, Ruijie He, Helen Kretzler, Matthias Jim, Belinda Cohen, Clemens D. He, John C. TI Alteration of Forkhead Box O (Foxo4) Acetylation Mediates Apoptosis of Podocytes in Diabetes Mellitus SO PLOS ONE LA English DT Article ID TRANSCRIPTION FACTOR ACETYLATION; GENE-EXPRESSION; GLOMERULAR-DISEASE; OXIDATIVE STRESS; OXIDANT STRESS; SIRT1; NEPHROPATHY; ACTIVATION; GLYCATION; INJURY AB The number of kidney podocytes is reduced in diabetic nephropathy. Advanced glycation end products (AGEs) accumulate in patients with diabetes and promote the apoptosis of podocyte by activating the forkhead box O4 (Foxo4) transcription factor to increase the expression of a pro-apoptosis gene, Bcl2l11. Using chromatin immunoprecipitation we demonstrate that AGE-modified bovine serum albumin (AGE-BSA) enhances Foxo4 binding to a forkhead binding element in the promoter of Bcl2lll. AGE-BSA also increases the acetylation of Foxo4. Lysine acetylation of Foxo4 is required for Foxo4 binding and transcription of Bcl2l11 in podocytes treated with AGE-BSA. The expression of a protein deacetylase that targets Foxo4 for deacetylation, sirtuin (Sirt1), is down regulated in cultured podocytes by AGE-BSA treatment and in glomeruli of diabetic patients. SIRT1 over expression in cultured murine podocytes prevents AGE-induced apoptosis. Glomeruli isolated from diabetic db/db mice have increased acetylation of Foxo4, suppressed expression of Sirt1, and increased expression of Bcl2l11 compared to non-diabetic littermates. Together, our data provide evidence that alteration of Foxo4 acetylation and down regulation of Sirt1 expression in diabetes promote podocyte apoptosis. Strategies to preserve Sirt1 expression or reduce Foxo4 acetylation could be used to prevent podocyte loss in diabetes. C1 [Chuang, Peter Y.; Dai, Yan; He, Helen; He, John C.] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. [Dai, Yan; He, John C.] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 1, Dept Nephrol, Shanghai 200030, Peoples R China. [Liu, Ruijie] James J Peters VA Med Ctr, Bronx, NY USA. [Kretzler, Matthias] Univ Michigan, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA. [Jim, Belinda] Albert Einstein Coll Med, Jacobi Med Ctr, Dept Med, Div Nephrol, Bronx, NY 10467 USA. [Cohen, Clemens D.] Univ Zurich, Div Nephrol, Zurich, Switzerland. [Cohen, Clemens D.] Univ Zurich, Inst Physiol, Zurich, Switzerland. RP Chuang, PY (reprint author), Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. EM peter.chuang@mssm.edu FU NIH [DK082760R01]; Else Kroner-Fresenius Foundation [P09/05//A62/04]; U.S. Department of Veterans Affairs [1I01BX000345] FX This work is supported by an NIH career development award (DK082760R01) to P.Y.C., the Else Kroner-Fresenius Foundation (P09/05//A62/04) award to C. D. C., and a U.S. Department of Veterans Affairs Merit Review Award (1I01BX000345) to J.C.H. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 34 Z9 37 U1 3 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 17 PY 2011 VL 6 IS 8 AR e23566 DI 10.1371/journal.pone.0023566 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 810JJ UT WOS:000294121300061 PM 21858169 ER PT J AU Korenstein, D Keyhani, S Mendelson, A Ross, JS AF Korenstein, Deborah Keyhani, Salomeh Mendelson, Ali Ross, Joseph S. TI Adherence of Pharmaceutical Advertisements in Medical Journals to FDA Guidelines and Content for Safe Prescribing SO PLOS ONE LA English DT Article ID DRUG ADVERTISEMENTS; ACCURACY; QUALITY; PATIENT; LAW AB Background: Physician-directed pharmaceutical advertising is regulated in the United States by the Food and Drug Administration (FDA); adherence to current FDA guidelines is unknown. Our objective was to determine adherence rates of physician-directed print advertisements in biomedical journals to FDA guidelines and describe content important for safe prescribing. Methods and Findings: Cross-sectional analysis of November 2008 pharmaceutical advertisements within top U. S.-based biomedical journals publishing original research. We excluded advertisements for devices, over the counter medications, and disease awareness. We utilized FDA guideline items identifying unique forms of advertisement bias to categorize advertisements as adherent to FDA guidelines, possibly non-adherent to at least 1 item, or non-adherent to at least 1 item. We also evaluated advertisement content important for safe prescribing, including benefit quantification, risk information and verifiable references. All advertisements were evaluated by 2 or more investigators, with differences resolved by discussion. Twelve journals met inclusion criteria. Nine contained pharmaceutical advertisements, including 192 advertisements for 82 unique products; median 2 per product (range 1-14). Six "teaser" advertisements presented only drug names, leaving 83 full unique advertisements. Fifteen advertisements (18.1%) adhered to all FDA guidelines, 41 (49.4%) were non-adherent with at least one form of FDA-described bias, and 27 (32.5%) were possibly non-adherent due to incomplete information. Content important for safe prescribing was often incomplete; 57.8% of advertisements did not quantify serious risks, 48.2% lacked verifiable references and 28.9% failed to present adequate efficacy quantification. Study limitations included its focus on advertisements from a single month, the subjectivity of FDA guidelines themselves, and the necessary subjectivity of determinations of adherence. Conclusions: Few physician-directed print pharmaceutical advertisements adhere to all FDA guidelines; over half fail to quantify serious risks. The FDA could better protect public health by creating new more objective advertisement guidelines requiring transparent presentation of basic safety and efficacy information. C1 [Korenstein, Deborah] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Keyhani, Salomeh] Mt Sinai Sch Med, Dept Hlth Evidence & Policy, New York, NY USA. [Keyhani, Salomeh] James J Peters VA Med Ctr, HSR&D Res Enhancement Award Program, Bronx, NY USA. [Keyhani, Salomeh] James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. [Mendelson, Ali] Weill Cornell Med Coll, New York, NY USA. [Ross, Joseph S.] Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, New Haven, CT 06510 USA. [Ross, Joseph S.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Korenstein, D (reprint author), Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. EM deborah.korenstein@mssm.edu FU NIA NIH HHS [K08 AG032886] NR 25 TC 8 Z9 8 U1 2 U2 13 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 AUG 17 PY 2011 VL 6 IS 8 AR e23336 DI 10.1371/journal.pone.0023336 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 810JJ UT WOS:000294121300037 PM 21858076 ER PT J AU Ommaya, AK Kupersmith, J AF Ommaya, Alexander K. Kupersmith, Joel TI Challenges Facing the US Patient-Centered Outcomes Research Institute SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CLINICAL-RESEARCH ENTERPRISE C1 [Ommaya, Alexander K.; Kupersmith, Joel] US Dept Vet Affairs, Off Res & Dev, Washington, DC 20420 USA. RP Ommaya, AK (reprint author), US Dept Vet Affairs, Off Res & Dev, 810 Vermont Ave NW, Washington, DC 20420 USA. EM alex.ommaya@va.gov NR 8 TC 5 Z9 5 U1 0 U2 3 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 AUG 17 PY 2011 VL 306 IS 7 BP 756 EP 757 DI 10.1001/jama.2011.1171 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 807LP UT WOS:000293900000026 PM 21846858 ER PT J AU Hung, WW Morrison, RS AF Hung, William W. Morrison, R. Sean TI Hip Fracture: A Complex Illness Among Complex Patients SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID PROXIMAL FEMORAL FRACTURES; HOSPITAL DISCHARGE; RISK-FACTORS; OUTCOMES; SURGERY; MORTALITY; CARE; SURVIVAL; PAIN C1 [Hung, William W.; Morrison, R. Sean] Mt Sinai Sch Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. [Hung, William W.] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Hung, WW (reprint author), Mt Sinai Sch Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. FU NIA NIH HHS [K24 AG022345, R01AG030141]; PHS HHS [AGK24AG022345] NR 20 TC 10 Z9 10 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 16 PY 2011 VL 155 IS 4 BP 267 EP + DI 10.7326/0003-4819-155-4-201108160-00012 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 807KN UT WOS:000293896400009 PM 21844553 ER PT J AU Peterson, PN Rumsfeld, JS AF Peterson, Pamela N. Rumsfeld, John S. TI The Evolving Story of Guidelines and Health Care: Does Being NICE Help? SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID CHRONIC HEART-FAILURE; TASK-FORCE; ASSOCIATION; RECOMMENDATIONS; COLLABORATION; MANAGEMENT; DIAGNOSIS; SOCIETY; ADULTS; COSTS C1 [Rumsfeld, John S.] Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. [Peterson, Pamela N.] Denver Hlth Med Ctr, Denver, CO 80204 USA. RP Rumsfeld, JS (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM John.Rumsfeld@va.gov NR 18 TC 2 Z9 2 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 16 PY 2011 VL 155 IS 4 BP 269 EP + DI 10.7326/0003-4819-155-4-201108160-00013 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 807KN UT WOS:000293896400010 PM 21844554 ER PT J AU Litvan, I Aarsland, D Adler, CH Goldman, JG Kulisevsky, J Mollenhauer, B Rodriguez-Oroz, MC Troster, AI Weintraub, D AF Litvan, Irene Aarsland, Dag Adler, Charles H. Goldman, Jennifer G. Kulisevsky, Jaime Mollenhauer, Brit Rodriguez-Oroz, Maria C. Troester, Alexander I. Weintraub, Daniel TI MDS Task Force on Mild Cognitive Impairment in Parkinson's Disease: Critical Review of PD-MCI SO MOVEMENT DISORDERS LA English DT Review DE mild cognitive impairment; Parkinson's disease; systematic review ID PROGRESSIVE SUPRANUCLEAR PALSY; CSF AMYLOID-BETA; REVISED CAMCOG-R; QUALITY-OF-LIFE; LEWY BODIES; CEREBROSPINAL-FLUID; DIFFERENTIAL-DIAGNOSIS; COMMUNITY POPULATION; NORWEGIAN PARKWEST; CLINICAL-FEATURES AB There is controversy regarding the definition and characteristics of mild cognitive impairment in Parkinson's disease. The Movement Disorder Society commissioned a Task Force to critically evaluate the literature and determine the frequency and characteristics of Parkinson's disease-mild cognitive impairment and its association with dementia. A comprehensive PubMed literature review was conducted using systematic inclusion and exclusion criteria. A mean of 26.7% (range, 18.9%-38.2%) of nondemented patients with Parkinson's disease have mild cognitive impairment. The frequency of Parkinson's disease-mild cognitive impairment increases with age, disease duration, and disease severity. Impairments occur in a range of cognitive domains, but single domain impairment is more common than multiple domain impairment, and within single domain impairment, nonamnestic is more common than amnestic impairment. A high proportion of patients with Parkinson's disease-mild cognitive impairment progress to dementia in a relatively short period of time. The primary conclusions of the Task Force are that: (1) Parkinson's disease-mild cognitive impairment is common, (2) there is significant heterogeneity within Parkinson's disease-mild cognitive impairment in the number and types of cognitive domain impairments, (3) Parkinson's disease-mild cognitive impairment appears to place patients at risk of progressing to dementia, and (4) formal diagnostic criteria for Parkinson's disease-mild cognitive impairment are needed. (C)2011 Movement Disorder Society C1 [Litvan, Irene] Univ Louisville, Sch Med, Dept Neurol, Div Movement Disorders, Louisville, KY 40241 USA. [Litvan, Irene] Frazier Rehab Neurosci Inst, Movement Disorders Program, Louisville, KY USA. [Aarsland, Dag] Stavanger Univ Hosp, Ctr Age Related Med, Oslo, Norway. [Aarsland, Dag] Univ Oslo, Akershus Univ Hosp, Oslo, Norway. [Adler, Charles H.] Mayo Clin, Dept Neurol, Parkinsons Dis & Movement Disorders Ctr, Scottsdale, AZ USA. [Goldman, Jennifer G.] Rush Univ, Med Ctr, Sect Parkinson Dis & Movement Disorders, Dept Neurol Sci, Chicago, IL 60612 USA. [Kulisevsky, Jaime] St Pau Hosp, Dept Neurol, Movement Disorders Unit, Madrid, Spain. [Kulisevsky, Jaime] Univ Autonoma Barcelona, Inst Biomed Res IIB St Pau, Madrid, Spain. [Kulisevsky, Jaime; Rodriguez-Oroz, Maria C.] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain. [Mollenhauer, Brit] Univ Gottingen, Paracelsus Elena Klin, Gottingen, Germany. [Rodriguez-Oroz, Maria C.] Univ Navarra Clin, Dept Neurol, Sch Med, Ctr Neurosci,CIMA, Pamplona, Spain. [Troester, Alexander I.] Univ N Carolina, Sch Med, Dept Neurol, Chapel Hill, NC 27599 USA. [Weintraub, Daniel] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, PADRECC, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, MIRECC, Philadelphia, PA USA. RP Litvan, I (reprint author), Univ Louisville, Sch Med, Dept Neurol, Div Movement Disorders, 220 Abraham Flexner Way,Ste 1503, Louisville, KY 40241 USA. EM i.litvan@louisville.edu OI Aarsland, Dag/0000-0001-6314-216X; Litvan, Irene/0000-0002-3485-3445 FU Arizona Biomedical Research Commission; Michael J. Fox Foundation; National Parkinson Foundation; GlaxoSmithKline; Medtronic, Inc.; [5R01AG024040-04] FX Irene Litvan was funded by 5R01AG024040-04. Charles Adler has been a consultant for Ipsen and Merck Serono, has been on the advisory boards of Biogen Idec, Eli Lilly, Medtronic, and Merz, and has received grants from the Arizona Biomedical Research Commission and the Michael J. Fox Foundation. Alexander I. Troster has been a consultant for Medtronic, Inc., St. Jude, and Boston Scientific, has been on the advisory boards of Medtronic, Inc. and St. Jude, has received honoraria from Medtronic and Boehringer Ingelheim, and has received grants from the National Parkinson Foundation, GlaxoSmithKline, and Medtronic, Inc. NR 109 TC 206 Z9 215 U1 5 U2 41 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 AUG 15 PY 2011 VL 26 IS 10 BP 1814 EP 1824 DI 10.1002/mds.23823 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 822DS UT WOS:000295024700006 PM 21661055 ER PT J AU Penuelas, O Frutos-Vivar, F Fernandez, C Anzueto, A Epstein, SK Apezteguia, C Gonzalez, M Nin, N Raymondos, K Tomicic, V Desmery, P Arabi, Y Pelosi, P Kuiper, M Jibaja, M Matamis, D Ferguson, ND Esteban, A AF Penuelas, Oscar Frutos-Vivar, Fernando Fernandez, Cristina Anzueto, Antonio Epstein, Scott K. Apezteguia, Carlos Gonzalez, Marco Nin, Nicolas Raymondos, Konstantinos Tomicic, Vinko Desmery, Pablo Arabi, Yaseen Pelosi, Paolo Kuiper, Michael Jibaja, Manuel Matamis, Dimitros Ferguson, Niall D. Esteban, Andres CA Ventila Grp TI Characteristics and Outcomes of Ventilated Patients According to Time to Liberation from Mechanical Ventilation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE mechanical ventilation; weaning; outcome; extubation ID CRITICAL ILLNESS POLYNEUROPATHY; SPONTANEOUS BREATHING TRIAL; ACUTE RESPIRATORY-DISTRESS; DURATION; SEDATION; PROTOCOL; FAILURE AB Rationale: A new classification of patients based on the duration of liberation of mechanical ventilation has been proposed. Objectives: To analyze outcomes based on the new weaning classification in a cohort of mechanically ventilated patients. Methods: Secondary analysis included 2,714 patients who were weaned and underwent scheduled extubation from a cohort of 4,968 adult patients mechanically ventilated for more than 12 hours. Measurements and Main Results: Patients were classified according to a new weaning classification: 1,502 patients (55%) as simple weaning, 1,058 patients (39%) as difficult weaning, and 154 (6%) as prolonged weaning. Variables associated with prolonged weaning(>7 d) were: severity at admission (odds ratio [OR] per unit of Simplified Acute Physiology Score II, 1.01; 95% confidence interval [CI], 1.001-1.02), duration of mechanical ventilation before first attempt of weaning (OR per day, 1.10; 95% CI, 1.06-1.13), chronic pulmonary disease other than chronic obstructive pulmonary disease (OR, 13.23; 95% CI, 3.44-51.05), pneumonia as the reason to start mechanical ventilation (OR, 1.82; 95% CI, 1.07-3.08), and level of positive end-expiratory pressure applied before weaning (OR per unit, 1.09; 95% CI, 1.04-1.14). The prolonged weaning group had a nonsignificant trend toward a higher rate of reintubation (P = 0.08), tracheostomy (P = 0.15), and significantly longer length of stay and higher mortality in the intensive care unit (OR for death, 1.97; 95% CI, 1.17-3.31). The adjusted probability of death remained constant until Day 7, at which point it increased to 12.1%. Conclusions: Only patients who need more than 7 days for weaning have an increased mortality. C1 [Esteban, Andres] Hosp Univ Getafe, Intens Care Unit, Madrid 28905, Spain. [Penuelas, Oscar; Frutos-Vivar, Fernando; Nin, Nicolas; Esteban, Andres] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Fernandez, Cristina] Hosp Clin San Carlos, Dept Clin Epidemiol & Prevent Med, Madrid, Spain. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, Antonio] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Ferguson, Niall D.] Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Ferguson, Niall D.] Univ Hlth Network, Interdept Div Crit Care Med, Toronto, ON, Canada. [Ferguson, Niall D.] Univ Hlth Network, Div Respirol, Dept Med, Toronto, ON, Canada. [Epstein, Scott K.] Tufts Univ, Sch Med, Off Educ Affairs, Boston, MA 02111 USA. [Apezteguia, Carlos] Hosp Prof A Posadas, Buenos Aires, DF, Argentina. [Gonzalez, Marco] Univ Pontificia Bolivariana, Medellin, Colombia. [Gonzalez, Marco] Clin Medellin, Medellin, Colombia. [Raymondos, Konstantinos] Hannover Med Sch, D-30623 Hannover, Germany. [Tomicic, Vinko] Clin Las Lilas, Santiago, Chile. [Desmery, Pablo] Sanat Mitre, Buenos Aires, DF, Argentina. [Arabi, Yaseen] King Saud Bin Abdulaziz Univ Hlth Sci, Riyadh, Saudi Arabia. [Pelosi, Paolo] Univ Genoa, Dipartimento Sci Chirurg & Diagnost Int, Genoa, Italy. [Kuiper, Michael] Med Ctr Leeuwarden, Leeuwarden, Netherlands. [Jibaja, Manuel] Hosp Mil Quito, Quito, Ecuador. [Matamis, Dimitros] Papageorgiou Gen Hosp, Thessaloniki, Greece. 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; koca, ugur/0000-0002-2949-4265; Kuiper, Michael/0000-0001-6201-7332; Darmon, Michael/0000-0003-4198-8038; Malbrain, Manu/0000-0002-1816-5255; Severgnini, Paolo/0000-0001-8027-0059; Frutos-Vivar, Fernando/0000-0002-4648-9636; Ost, David/0000-0001-6351-5552; Ferguson, Niall/0000-0002-6213-5264 FU CIBER Enfermedades Respiratorias from Instituto de Salud Carlos III, Spain; Canadian Institutes of Health Research (Ottawa, Canada); Best Spanish Clinical Researcher, Lilly Award (Spain) FX Supported by CIBER Enfermedades Respiratorias from Instituto de Salud Carlos III, Spain. N.D.F. is supported by a Canadian Institutes of Health Research New Investigator Award (Ottawa, Canada). A. E. is supported by the Best Spanish Clinical Researcher, Lilly Award (Spain). NR 21 TC 73 Z9 81 U1 0 U2 10 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 15 PY 2011 VL 184 IS 4 BP 430 EP 437 DI 10.1164/rccm.201011-1887OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 808EL UT WOS:000293959600013 PM 21616997 ER PT J AU Kulkarni, H Okulicz, JF Grandits, G Crum-Cianflone, NF Landrum, ML Hale, B Wortmann, G Tramont, E Polis, M Dolan, M Lifson, AR Agan, BK Ahuja, SK Marconi, VC AF Kulkarni, Hemant Okulicz, Jason F. Grandits, Greg Crum-Cianflone, Nancy F. Landrum, Michael L. Hale, Braden Wortmann, Glenn Tramont, Edmund Polis, Michael Dolan, Matthew Lifson, Alan R. Agan, Brian K. Ahuja, Sunil K. Marconi, Vincent C. TI Early Postseroconversion CD4 Cell Counts Independently Predict CD4 Cell Count Recovery in HIV-1-Postive Subjects Receiving Antiretroviral Therapy SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE CD4 count; highly active antiretroviral therapy; outcomes; predictors; treatment response ID PLASMA HIV RNA; VIROLOGICAL RESPONSES; HIV-1-INFECTED PATIENTS; IMMUNOLOGICAL RESPONSE; DISEASE PROGRESSION; PROTEASE INHIBITOR; INFECTED PATIENTS; IMMUNODEFICIENCY; SUPPRESSION; INTERRUPTION AB Background: The relationship between CD4(+) T-cell counts determined soon after seroconversion with HIV-1 (baseline CD4), nadir CD4, and CD4 levels attained during highly active antiretroviral therapy (HAART) is unknown. Methods: Longitudinal, including baseline (at or soon after HIV diagnosis), intermediate (nadir), and distal (post-HAART) CD4(+) T-cell counts were assessed in 1085 seroconverting subjects who achieved viral load suppression from a large well-characterized cohort. The association of baseline with post-HAART CD4(+) T-cell count was determined after adjustment for other relevant covariates. Results: A higher baseline CD4(+) T-cell count predicted a greater postHAART CD4(+) T-cell count, independent of the nadir and other explanatory variables. Together, baseline and nadir strongly predicted the post-HAART CD4(+) count such that a high baseline and lower nadir were associated with a maximal immune recovery after HAART. Likelihood of recovery of the baseline count after HAART was significantly higher when the nadir/ baseline count ratio was consistently >= 0.6. Conclusions: Among viral load suppressing seroconverters, the absolute CD4(+) T-cell count attained post-HAART is highly dependent on both baseline and nadir CD4(+) T-cell counts. These associations further support the early diagnosis and initiation of HAART among HIV-infected persons. C1 [Kulkarni, Hemant; Ahuja, Sunil K.] S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV Infect 1, San Antonio, TX USA. [Kulkarni, Hemant; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Okulicz, Jason F.; Grandits, Greg; Crum-Cianflone, Nancy F.; Landrum, Michael L.; Hale, Braden; Wortmann, Glenn; Tramont, Edmund; Polis, Michael; Agan, Brian K.; Marconi, Vincent C.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA. [Okulicz, Jason F.; Landrum, Michael L.] Brooke Army Med Ctr, San Antonio Mil Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA. [Grandits, Greg] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Crum-Cianflone, Nancy F.; Hale, Braden] USN, Infect Dis Clin, San Diego Med Ctr, San Diego, CA 92152 USA. [Wortmann, Glenn] Walter Reed Army Med Ctr, Infect Dis Serv, Washington, DC 20307 USA. [Tramont, Edmund; Polis, Michael] NIAID, NIH, Bethesda, MD 20892 USA. [Dolan, Matthew] Wilford Hall USAF Med Ctr, Henry M Jackson Fdn, Lackland AFB, TX 78236 USA. [Lifson, Alan R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol & Biochem, San Antonio, TX 78229 USA. [Marconi, Vincent C.] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA USA. RP Kulkarni, H (reprint author), 12023 Waterway Rdg, San Antonio, TX USA. EM kulkarnih@uthscsa.edu RI Marconi, Vincent/N-3210-2014 OI Marconi, Vincent/0000-0001-8409-4689; Polis, Michael/0000-0002-9151-2268; Agan, Brian/0000-0002-5114-1669 FU Infectious Disease Clinical Research Program (IDCRP) [IDCRP-000-03]; Department of Defense; National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) [Y1-AI-5072]; Veterans Administration Center on AIDS and HIV infection of the South Texas Veterans Health Care System; NIH [R37046326]; VA MERIT award; Elizabeth Glaser Scientist Award; Burroughs Wellcome Clinical Scientist Award in Translational Research; Doris Duke Distinguished Clinical Scientist Award FX Support for this work (IDCRP-000-03) was provided by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense program executed through the Uniformed Services University of the Health Sciences. This project has been funded in whole, or in part, with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), under Inter-Agency Agreement Y1-AI-5072. This work was also supported by the Veterans Administration Center on AIDS and HIV infection of the South Texas Veterans Health Care System, and a MERIT (R37046326) award from the NIH to S. K. A. S. K. A. is also supported by a VA MERIT award and is a recipient of the Elizabeth Glaser Scientist Award, the Burroughs Wellcome Clinical Scientist Award in Translational Research, and the Doris Duke Distinguished Clinical Scientist Award. The content of this publication is the sole responsibility of the authors and does not necessarily reflect the views or policies of the NIH or the Department of Health and Human Services, the Department of Defense or the Departments of the Army, Navy or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the US Government. NR 45 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 15 PY 2011 VL 57 IS 5 BP 387 EP 395 DI 10.1097/QAI.0b013e3182219113 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 800RE UT WOS:000293381300013 PM 21546844 ER PT J AU Clancy, CJ Nguyen, MH AF Clancy, Cornelius J. Nguyen, M. Hong TI At What Cost Echinocandin Resistance? SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID CANDIDA-ALBICANS; DRUG-RESISTANCE; INVASIVE CANDIDIASIS; FITNESS; EVOLUTION; SUSCEPTIBILITY; MECHANISMS C1 [Clancy, Cornelius J.; Nguyen, M. Hong] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Clancy, Cornelius J.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Clancy, CJ (reprint author), 3550 Terrace St,Scaife Hall 867, Pittsburgh, PA 15261 USA. EM cjc76@pitt.edu NR 19 TC 5 Z9 5 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 15 PY 2011 VL 204 IS 4 BP 499 EP 501 DI 10.1093/infdis/jir355 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 799RS UT WOS:000293304400003 PM 21791650 ER PT J AU Hannun, YA Obeid, LM AF Hannun, Yusuf A. Obeid, Lina M. TI Many Ceramides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID NECROSIS-FACTOR-ALPHA; RADIATION-INDUCED APOPTOSIS; LONGEVITY ASSURANCE GENE-1; TANDEM MASS-SPECTROMETRY; SQUAMOUS-CELL CARCINOMAS; SPHINGOLIPID METABOLISM; SACCHAROMYCES-CEREVISIAE; SPHINGOSINE 1-PHOSPHATE; SYNTHASE 6; NEUTRAL SPHINGOMYELINASE-2 AB Intensive research over the past 2 decades has implicated ceramide in the regulation of several cell responses. However, emerging evidence points to dramatic complexities in ceramide metabolism and structure that defy the prevailing unifying hypothesis on ceramide function that is based on the understanding of ceramide as a single entity. Here, we develop the concept that "ceramide" constitutes a family of closely related molecules, subject to metabolism by >28 enzymes and with >200 structurally distinct mammalian ceramides distinguished by specific structural modifications. These ceramides are synthesized in a combinatorial fashion with distinct enzymes responsible for the specific modifications. These multiple pathways of ceramide generation led to the hypothesis that individual ceramide molecular species are regulated by specific biochemical pathways in distinct subcellular compartments and execute distinct functions. In this minireview, we describe the "many ceramides" paradigm, along with the rationale, supporting evidence, and implications for our understanding of bioactive sphingolipids and approaches for unraveling these pathways. C1 [Hannun, Yusuf A.; Obeid, Lina M.] 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 Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. EM hannun@musc.edu; obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU National Institutes of Health [R01AG016583, R01GM062887]; NCI [R01GM43825, R01GM63265, P01CA097132]; Office of Research and Development, Department of Veterans Affairs; Ralph H. Johnson Veterans Affairs Medical Center (Charleston, SC) FX This work was support, in whole or in part, by National Institutes of Health Grants R01AG016583 and R01GM062887 (to L. M. O.) and R01GM43825, R01GM63265, and P01CA097132 from NCI (to Y. A. H.) and in part by a MERIT Award (to L. M. O.) from the Office of Research and Development, Department of Veterans Affairs, Ralph H. Johnson Veterans Affairs Medical Center (Charleston, SC). This minireview will be reprinted in the 2011 Minireview Compendium, which will be available in January, 2012. NR 96 TC 199 Z9 202 U1 0 U2 22 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 AUG 12 PY 2011 VL 286 IS 32 BP 27855 EP 27862 DI 10.1074/jbc.R111.254359 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 803CJ UT WOS:000293557800002 PM 21693702 ER PT J AU Zou, CB Ellis, BM Smith, RM Chen, BB Zhao, YT Mallampalli, RK AF Zou, Chunbin Ellis, Bryon M. Smith, Rebecca M. Chen, Bill B. Zhao, Yutong Mallampalli, Rama K. TI Acyl-CoA:Lysophosphatidylcholine Acyltransferase I (Lpcat1) Catalyzes Histone Protein O-Palmitoylation to Regulate mRNA Synthesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLCHOLINE SYNTHESIS; CHROMATIN-STRUCTURE; PHOSPHORYLATION; MAINTENANCE; DROSOPHILA; STABILITY; HORMONE; YEAST; COA AB The enzyme acyl-CoA:lysophosphatidylcholine acyltransferase (Lpcat1) is a critical cytosolic enzyme needed for lung surfactant synthesis that catalyzes an acyltransferase reaction by adding a palmitate to the sn-2 position of lysophospholipids. Here we report that histone H4 protein is subject to palmitoylation catalyzed by Lpcat1 in a calcium-regulated manner. Cytosolic Lpcat1 was observed to shift into the nucleus in lung epithelia in response to exogenous Ca(2+). Nuclear Lpcat1 colocalizes with and binds to histone H4, where it catalyzes histone H4 palmitoylation. Mutagenesis studies demonstrated that Ser(47) within histone H4 serves as a putative acceptor site, indicative of Lpcat1-mediated O-palmitoylation. Lpcat1 knockdown or expression of a histone H4 Ser(47A) mutant protein in cells decreased cellular mRNA synthesis. These findings provide the first evidence of a protein substrate for Lpcat1 and reveal that histone lipidation may occur through its O-palmitoylation as a novel post-translational modification. This epigenetic modification regulates global gene transcriptional activity. C1 [Zou, Chunbin] Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. RP Zou, CB (reprint author), Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, Acute Lung Injury Ctr Excellence, BST E1 103,200 Lathrop St, Pittsburgh, PA 15213 USA. EM zouc@upmc.edu FU National Institutes of Health [R01 HL096376, HL097376, HL098174]; United States Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; United States Department of Veterans Affairs FX This work was supported, in whole or in part, by National Institutes of Health Grants R01 HL096376, HL097376, and HL098174 (to R. K. M.). This material is based upon work supported, in part, by the United States Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. This work was also supported by a Merit Review Award from the United States Department of Veterans Affairs. NR 30 TC 26 Z9 27 U1 1 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 AUG 12 PY 2011 VL 286 IS 32 BP 28019 EP 28025 DI 10.1074/jbc.M111.253385 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 803CJ UT WOS:000293557800020 PM 21685381 ER PT J AU Hsieh, KC Gvilia, I Kumar, S Uschakov, A McGinty, D Alam, MN Szymusiak, R AF Hsieh, K. -C. Gvilia, I. Kumar, S. Uschakov, A. McGinty, D. Alam, M. N. Szymusiak, R. TI c-FOS EXPRESSION IN NEURONS PROJECTING FROM THE PREOPTIC AND LATERAL HYPOTHALAMIC AREAS TO THE VENTROLATERAL PERIAQUEDUCTAL GRAY IN RELATION TO SLEEP STATES SO NEUROSCIENCE LA English DT Article DE median preoptic nucleus; ventrolateral preoptic area; perifornical lateral hypothalamus; sleep deprivation ID WAKING DISCHARGE PATTERNS; EYE-MOVEMENT SLEEP; REM-SLEEP; IMMUNOREACTIVE NEURONS; PARADOXICAL SLEEP; STRIA TERMINALIS; OREXIN NEURONS; PARAVENTRICULAR NUCLEUS; HOMEOSTATIC REGULATION; BEHAVING ANIMALS AB The ventrolateral division of the periaqueductal gray (vIPAG) and the adjacent deep mesencephalic reticular nucleus have been implicated in the control of sleep. The preoptic hypothalamus, which contains populations of sleep-active neurons, is an important source of afferents to the vIPAG. The perifornical lateral hypothalamus (LH) contains populations of wake-active neurons and also projects strongly to the vIPAG. We examined nonREM and REM sleep-dependent expression of c-Fos protein in preoptic-vIPAG and LH-vIPAG projection neurons identified by retrograde labeling with Fluorogold (FG). Separate groups of rats (n=5) were subjected to 3 h total sleep deprivation (TSD) followed by 1 h recovery sleep (RS), or to 3 h of selective REM sleep deprivation (RSD) followed by RS. A third group of rats (n=5) was subjected to TSD without opportunity for RS (awake group). In the median preoptic nucleus (MnPN), the percentage of FG+ neurons that were also Fos+ was higher in TSD-RS animals compared to both RSD-RS rats and awake rats. There were significant correlations between time spent in deep nonREM sleep during the 1 h prior to sacrifice across groups and the percentage of double-labeled cells in MnPN and ventrolateral preoptic area (VLPO). There were no significant correlations between percentage of double-labeled neurons and time spent in REM sleep for any of the preoptic nuclei examined. In the LH, percentage of double-labeled neurons was highest in awake rats, intermediate in TSD-RS rats and lowest in the RSD-RS group. These results suggest that neurons projecting from MnPN and VLPO to the vIPAG are activated during nonREM sleep and support the hypothesis that preoptic neurons provide inhibitory input to vIPAG during sleep. Suppression of excitatory input to the vIPAG from the LH during sleep may have a permissive effect on REM sleep generation. Published by Elsevier Ltd on behalf of IBRO. C1 [Hsieh, K. -C.; Gvilia, I.; Kumar, S.; Uschakov, A.; McGinty, D.; Alam, M. N.; Szymusiak, R.] VA Greater Los Angeles, Res Serv, Los Angeles, CA 91343 USA. [Hsieh, K. -C.; Kumar, S.; Uschakov, A.; Szymusiak, R.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Hsieh, K. -C.; Kumar, S.; Uschakov, A.; Szymusiak, R.] Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90024 USA. [Gvilia, I.] Beritashvili Inst Physiol, Tbilisi, GA USA. [McGinty, D.; Alam, M. N.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Szymusiak, R (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM rszym@ucla.edu FU Department of Veterans Affairs; NIH [MH63323] FX Supported by the Department of Veterans Affairs and NIH Grant MH63323. The authors thank Ms. Keng-Tee Chow and Mr. Bryan Angara for their excellent technical assistance. NR 69 TC 13 Z9 14 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD AUG 11 PY 2011 VL 188 BP 55 EP 67 DI 10.1016/j.neuroscience.2011.05.016 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 783GL UT WOS:000292069400006 PM 21601616 ER PT J AU Peralta, CA Shlipak, MG AF Peralta, Carmen A. Shlipak, Michael G. TI Biomarkers for Detecting and Risk-Stratifying Chronic Kidney Disease Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID CYSTATIN-C; SERUM CYSTATIN; CREATININE C1 [Peralta, Carmen A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Peralta, CA (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM carmenalicia.peralta@ucsf.edu NR 4 TC 0 Z9 0 U1 1 U2 2 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 AUG 10 PY 2011 VL 306 IS 6 BP 611 EP 612 DI 10.1001/jama.2011.1112 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 804XD UT WOS:000293687300021 ER PT J AU Yaffe, K Laffan, AM Harrison, SL Redline, S Spira, AP Ensrud, KE Ancoli-Israel, S Stone, KL AF Yaffe, Kristine Laffan, Alison M. Harrison, Stephanie Litwack Redline, Susan Spira, Adam P. Ensrud, Kristine E. Ancoli-Israel, Sonia Stone, Katie L. TI Sleep-Disordered Breathing, Hypoxia, and Risk of Mild Cognitive Impairment and Dementia in Older Women SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MINI-MENTAL-STATE; HEART HEALTH; CARDIOVASCULAR-DISEASE; INTERMITTENT HYPOXIA; ALZHEIMERS-DISEASE; INSULIN-RESISTANCE; NOCTURNAL HYPOXIA; ANIMAL-MODELS; APNEA; FRAGMENTATION AB Context Sleep-disordered breathing (characterized by recurrent arousals from sleep and intermittent hypoxemia) is common among older adults. Cross-sectional studies have linked sleep-disordered breathing to poor cognition; however, it remains unclear whether sleep-disordered breathing precedes cognitive impairment in older adults. Objectives To determine the prospective relationship between sleep-disordered breathing and cognitive impairment and to investigate potential mechanisms of this association. Design, Setting, and Participants Prospective sleep and cognition study of 298 women without dementia (mean [SD] age: 82.3 [3.2] years) who had overnight polysomnography measured between January 2002 and April 2004 in a substudy of the Study of Osteoporotic Fractures. Sleep-disordered breathing was defined as an apnea-hypopnea index of 15 or more events per hour of sleep. Multivariate logistic regression was used to determine the independent association of sleep-disordered breathing with risk of mild cognitive impairment or dementia, adjusting for age, race, body mass index, education level, smoking status, presence of diabetes, presence of hypertension, medication use (antidepressants, benzodiazepines, or nonbenzodiazepine anxiolytics), and baseline cognitive scores. Measures of hypoxia, sleep fragmentation, and sleep duration were investigated as underlying mechanisms for this relationship. Main Outcome Measures Adjudicated cognitive status (normal, dementia, or mild cognitive impairment) based on data collected between November 2006 and September 2008. Results Compared with the 193 women without sleep-disordered breathing, the 105 women (35.2%) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (31.1% [n=60] vs 44.8% [n=47]; adjusted odds ratio [AOR], 1.85; 95% confidence interval [CI], 1.11-3.08). Elevated oxygen desaturation index (>= 15 events/hour) and high percentage of sleep time (>7%) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR, 1.71 [95% CI, 1.04-2.83] and AOR, 2.04 [95% CI, 1.10-3.78], respectively). Measures of sleep fragmentation (arousal index and wake after sleep onset) or sleep duration (total sleep time) were not associated with risk of cognitive impairment. Conclusion Among older women, those with sleep-disordered breathing compared with those without sleep-disordered breathing had an increased risk of developing cognitive impairment. JAMA. 2011;306(6):613-619 www.jama.com C1 [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94121 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Laffan, Alison M.; Harrison, Stephanie Litwack; Stone, Katie L.] Calif Pacific Med Ctr, San Francisco Coordinating Ctr, San Francisco, CA USA. [Redline, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Sleep Med, Boston, MA 02115 USA. [Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02115 USA. [Spira, Adam P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Epidemiol, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Community Hlth, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Vet Affairs Med Ctr, Minneapolis, MN USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu FU National Institutes of Health; Alzheimer Association; Department of Defense; American Health Assistance Foundation; Beeson Scientific; Japan Geriatrics Society; Wake Forest University; State of California Department of Human Services; National Institute on Aging [AG05407, AR35582, AG05394, AR35584, AR35583, R01 AG005407, R01 AG027576-22, 2 R01 AG005394-22A1, 2 R01 AG027574-22A1, AG026720, K24AG031155, AG08415]; NIA [1K01AG033195] FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Yaffe reported that she is a consultant for Novartis Inc; serves on data and safety monitoring boards for Pfizer, Medivation, and the National Institute of Mental Health; is a board member for Beeson Scientific Advisory; has grants pending with the National Institutes of Health, the Alzheimer Association, the Department of Defense, and the American Health Assistance Foundation; and has received funding for expenses unrelated to the activites listed from the Alzheimer Association, the National Institutes of Health, Beeson Scientific, Japan Geriatrics Society, Wake Forest University, and the State of California Department of Human Services. Dr Laffan reported that she received salary support and was reimbursed for travel to professional society meetings from the National Institutes of Health. Dr Redline reported that her institution received a California Pacific Medical Center subcontract via a National Institutes of Health grant; she is a board member for the American Academy of Sleep Medicine; her institution has received an endowment for a professorship in sleep medicine from Dr Peter Farrell, CEO of RosMed Inc; and has multiple grants pending with the National Institutes of Health on sleep apnea. Dr Spira reported that he has received honoraria as a clinical editor for the International Journal of Sleep and Wakefulness-Primary Care, which receives pharmaceutical industry support. Dr Ancoli-Israel reported that she is a consultant for Johnson & Johnson, Merck, Purdue Pharma LP, sanofi-aventis, and Pfizer and has grants pending with the National Institutes of Health. No other disclosures were reported.; The Study of Osteoporotic Fractures is supported by funding from the National Institutes of Health. The National Institute on Aging provided support for this study under grants AG05407, AR35582, AG05394, AR35584, AR35583, R01 AG005407, R01 AG027576-22, 2 R01 AG005394-22A1, and 2 R01 AG027574-22A1, AG05407, AR35582, AG05394, AR35584, AR35583, AG026720. In addition, this study was supported by National Institute on Aging grant AG026720. Dr Yaffe is supported in part by National Institute on Aging grant K24AG031155. Dr Spira is supported by a Mentored Research Scientist Development Award (NIA 1K01AG033195). Dr Ancoli-Israel is supported by National Institute on Aging grant AG08415. NR 43 TC 246 Z9 252 U1 5 U2 36 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 AUG 10 PY 2011 VL 306 IS 6 BP 613 EP 619 DI 10.1001/jama.2011.1115 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 804XD UT WOS:000293687300022 PM 21828324 ER EF